Cell biology Handout
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Cell biology Handout
Sources : - www.biologydaily.com www.biology.arizona.eduCell
biology (also called cellular biology or cytology) is an academic
discipline which studies the physiological properties of cells, as
well as their behaviours, interactions, and environment; this is
done both on a microscopic and molecular level. Cell biology
researches both single-celled organisms like bacteria and
specialized cells in multicellular organisms like humans.
Understanding the composition of cells and how cells works is
fundamental to all of the biological sciences. Appreciating the
similarities and differences between cell types is particularly
important to the fields of cell and molecular biology. These
fundamental similarities and differences provide a unifying theme,
allowing the principles learned from studying one cell type to be
extrapolated and generalized to other cell types. Research in cell
biology is closely related to genetics, biochemistry, molecular
biology and developmental biology.
Purification of cells and their parts Purification of cells and
their parts is achieved in the following ways: Cell
fractionation
Flow cytometry
Release of cellular organelles by disruption of cells.
Separation of different organelles by centrifugation.
Proteins extracted from membranes by detergents and salts.
The cell is the structural and functional unit of all living
organisms. Some organisms, such as bacteria, are unicellular,
consisting of a single cell. Other organisms, such as humans, are
multicellular, (humans have an estimated 100,000 billion = 1014
cells). The cell theory, first developed in the 19th century,
states that all organisms are composed of one or more cells; all
cells come from preexisting cells; all vital functions of an
organism occur within cells and that cells contain the hereditary
information necessary for regulating cell functions and for
transmitting information to the next generation of cells.
The word cell comes from the Latin cella, a small room. The name
was chosen by Robert Hooke because of the likeness he saw between
cork cells and small rooms.
Each cell is a self-contained and self-maintaining entity: it
can take in nutrients, convert these nutrients into energy, carry
out specialized functions, and reproduce as necessary. Each cell
stores its own set of instructions for carrying out each of these
activities.
All cells share several abilities:
Reproduction by cell division.
Metabolism, including taking in raw materials, building cell
components, creating energy molecules and releasing by-products.
The functioning of a cell depends upon its ability to extract and
use chemical energy stored in organic molecules. This energy is
derived from metabolic pathways.
Synthesis of proteins, the functional workhorses of cells, such
as enzymes. A typical mammalian cell contains up to 10,000
different proteins.
Response to external and internal stimuli such as changes in
temperature, pH or nutrient levels.
Traffic of vesicles.
Types of cells
One way to classify cells is whether they live alone or in
groups. Organisms vary from single cells (called single-celled or
unicellular organisms) that function and survive more or less
independently, through colonial forms with cells living together,
to multicellular forms in which cells are specialized and do not
generally survive once separated. 220 types of cells and tissues
make up the multicellular human body.
Cells can also be classified into two categories based on their
internal structure.
Prokaryotic cells are structurally simple. They are found only
in single-celled and colonial organisms. In the three-domain system
of scientific classification, prokaryotic cells are placed in the
domains Archaea and Eubacteria.
Eukaryotic cells have organelles with their own membranes.
Single-celled eukaryotic organisms are very diverse, but many
colonial and multicellular forms also exist. (The multicellular
kingdoms, i.e., Animalia, Plantae and Fungi, are all
eukaryotic.)
Components of cells
Schematic of typical animal cell. Organelles: (1) nucleolus (2)
nucleus (3) ribosome (4) vesicle,(5) rough endoplasmic reticulum
(ER), (6) Golgi apparatus, (7) Cytoskeleton, (8) smooth ER, (9)
mitochondria, (10) vacuole, (11) cytoplasm, (12) lysosome, (13)
centriolesAll cells whether prokaryotic or eukaryotic have a
membrane, which envelopes the cell, separates its interior from the
surroundings, strictly controls what moves in and out and maintains
the electric potential of the cell. Inside the membrane is a salty
cytoplasm (the substance which makes up most of the cell volume).
All cells possess DNA, the hereditary material of genes and RNA,
which contain the information necessary to express various proteins
such as enzyme, the cell's primary machinery. Within the cell at
any given time are various additional biomolecules. This article
will briefly overview these primary components of the cell then
continue to briefly describe their function.
Cell membrane - a cell's protective coat
The outer lining of a eukaryotic cell is called the plasma
membrane. A form of plasma membrane is also found in prokaryotes,
but in this organism it is usually referred to as the cell
membrane. This membrane serves to separate and protect a cell from
its surrounding environment and is made mostly from a double layer
of lipids (fat-like molecules) and proteins. Embedded within this
membrane are a variety of other molecules that act as channels and
pumps, moving different molecules into and out of the cell.
Cytoskeleton - a cell's scaffold
The cytoskeleton is an important, complex, and dynamic cell
component. It acts to organize and maintain the cell's shape;
anchors organelles in place; helps during endocytosis, the uptake
of external materials by a cell; and moves parts of the cell in
processes of growth and motility. There are a great number of
proteins associated with the cytoskeleton, each controlling a cells
structure by directing, bundling, and aligning filaments.
Cytoplasm - a cell's inner space
Inside the cell there is a large fluid-filled space called the
cytoplasm. This refers both to the mixture of ions and fluids in
solution within the cell, and the organelles contained in it which
are separated from this intercellular "soup" by their own
membranes. The cytosol refers only to the fluid, and not to the
organelles.
In prokaryotes, the cytoplasm is relatively free of
compartments. In eukaryotes, it normally contains a large number of
organelles, and is the home of the cytoskeleton. The cytosol
contains dissolved nutrients, helps break down waste products, and
moves material around the cell through a process called cytoplasmic
streaming. The nucleus often flows with the cytoplasm changing its
shape as it moves. The cytoplasm also contains many salts and is an
excellent conductor of electricity, creating the perfect
environment for the mechanics of the cell. The function of the
cytoplasm, and the organelles which reside in it, are critical for
a cell's survival.
Genetic material
Two different kinds of genetic material exist: deoxyribonucleic
acid (DNA) and ribonucleic acid (RNA). Most organisms use DNA for
their long term information storage, but a few viruses have RNA as
their genetic material. The biological information contained in an
organism is encoded in its DNA or RNA sequence. Note that RNA is
also used for information transport (mRNA) and enzymatic functions
(like ribosomal RNA) in most organisms.
Prokaryotic genetic material is organized in a simple circular
DNA molecule (the bacterial chromosome) that rests in the cytoplasm
(more specifically in the nucleoid region). Eukaryotic genetic
material is more complex (DNA is condensed with proteins) and is
divided into different, linear molecules called chromosomes, which
are found inside the nucleus and can come in an haploid or diploid
set. Besides some organelles have their own genetic material, which
is complemented by the nuclear genome (see endosymbiotic
theory).
Human genetic material, for example, is made up of two distinct
components: the nuclear genome and the mitochondrial genome. The
nuclear genome (being diploid) is divided into 46 linear DNA
molecules, each contained in a different chromosome. The
mitochondrial genome is a circular DNA molecule separate from the
nuclear DNA. Although the mitochondrial genome is very small, it
codes for some very important proteins.
Organelles
The human body contains many different organs, such as the
heart, lung, and kidney, with each organ performing a different
function. Cells also have a set of "little organs", called
organelles, that are adapted and/or specialized for carrying out
one or more vital functions. Organelles are found only in
eukaryotes and are, with a few exceptions, surrounded by a
protective membrane.
Cell nucleus - a cell's center: The cell nucleus is the most
conspicuous organelle found in a eukaryotic cell. It houses the
cell's chromosomes and is the place where almost all DNA
replication and RNA synthesis occur. The nucleus is spheroid in
shape and separated from the cytoplasm by a double membrane called
the nuclear envelope. The nuclear envelope isolates and protects a
cell's DNA from various molecules that could accidentally damage
its structure or interfere with its processing. During processing,
DNA is transcribed, or copied into a special RNA, called mRNA. This
mRNA is then transported out of the nucleus, where it is translated
into a specific protein molecule. In prokaryotes, DNA processing
takes place in the cytoplasm.
Ribosomes - the protein production machine: Ribosomes are found
in both prokaryotes and eukaryotes. The ribosome is a large complex
composed of many molecules, including RNAs and proteins, and is
responsible for processing the genetic instructions carried by an
mRNA. The process of converting an mRNA's genetic code into the
exact sequence of amino acids that make up a protein is called
translation. Protein synthesis is extremely important to all cells,
and therefore a large number of ribosomessometimes hundreds or even
thousandscan be found throughout a cell.
Mitochondria and chloroplasts - the power generators:
Mitochondria are self-replicating organelles that occur in various
numbers, shapes, and sizes in the cytoplasm of all eukaryotic
cells. As mentioned earlier, mitochondria contain their own genome
that is separate and distinct from the nuclear genome of a cell.
Mitochondria play a critical role in generating energy in the
eukaryotic cell, and this process involves a number of complex
metabolic pathways.
Endoplasmic reticulum and Golgi apparatus - macromolecule
managers:: The endoplasmic reticulum (ER) is the transport network
for molecules targeted for certain modifications and specific
destinations, as compared to molecules that will float freely in
the cytoplasm. The ER has two forms: the rough ER and the smooth
ER. The rough ER is labeled as such because it has ribosomes
adhering to its outer surface, whereas the smooth ER does not.
Translation of the mRNA for those proteins that will either stay in
the ER or be exported (moved out of the cell) occurs at the
ribosomes attached to the rough ER. Proteins to be exported are
passed to the Golgi apparatus, sometimes called a Golgi body or
Golgi complex, for further processing, packaging, and transport to
a variety of other cellular locations. The smooth ER serves for
lipids synthesis, detoxification and as a calcium reservoir.
Lysosomes and peroxisomes - the cellular digestive system:
Lysosomes and peroxisomes are often referred to as the garbage
disposal system of a cell. Both organelles are somewhat spherical,
bound by a single membrane, and rich in digestive enzymes,
naturally occurring proteins that speed up biochemical processes.
For example, lysosomes can contain more than three dozen enzymes
for degrading proteins, nucleic acids, and certain sugars called
polysaccharides. Here we can see the importance behind
compartmentalization of the eukaryotic cell. The cell could not
house such destructive enzymes if they were not contained in a
membrane-bound system.
Anatomy of cells
Eukaryotic cells are about 10 times the size of a prokaryote and
can be as much as 1000 times greater in volume. The major and
extremely significant difference between prokaryotes and eukaryotes
is that eukaryotic cells contain membrane-bound compartments in
which specific metabolic activities take place. Most important
among these is the presence of a nucleus, a membrane-delineated
compartment that houses the eukaryotic cells DNA. It is this
nucleus that gives the eukaryoteliterally, true nucleusits name.
Eukaryotic organisms also have other specialized structures,
performing dedicated functions, the aforementioned organelles.
Other differences include:
The cytoplasm of eukaryotes does not appear as granular as that
of prokaryotes, since an important part of the ribosomes are bound
to the endoplasmic reticulum.
The plasma membrane resembles that of prokaryotes in function,
with minor differences in the setup. Cell walls may or may not be
present.
The eukaryotic DNA is organized in one or more linear molecules,
called chromosomes, which are highly condensed (e.g. folded around
histones). All chromosomal DNA is stored in the cell nucleus,
separated from the cytoplasm by a membrane. Some eukaryotic
organelles can contain some DNA.
Eukaryotes can become mobile using cilia or flagella. The
flagella are more complex than those of prokaryotes.
Table 1: Comparison of features of prokaroytic and eukaryotic
cells
Prokaryotes Eukaryotes
Typical organisms bacteria, archaea protists, fungi, plants,
animals
Typical size ~ 1-10 m ~ 10-100 m (sperm cells, apart from the
tail, are smaller)
Type of nucleus nucleoid region; no real nucleus real nucleus
with double membrane
DNA circular (usually) linear molecules (chromosomes) with
histone proteins
RNA-/protein-synthesis coupled in cytoplasm RNA-synthesis inside
the nucleusprotein synthesis in cytoplasm
Ribosomes 50S+30S 60S+40S
Cytoplasmatic structure very few structures highly structured by
endomembranes and a cytoskeleton
Cell movement flagella made of flagellin flagella and cilia made
of tubulin
Mitochondria none one to several dozen (though some lack
mitochondria)
Chloroplasts none in algae and plants
Organization Usually single cells single cells, colonies, higher
multicellular organisms with specialized cells
Cell division Binary fission (simple division) Mitosis
Meiosis
Cell functions
Cell growth and metabolism
Between successive cell divisions cells grow through the
functioning of cellular metabolism. Cell metabolism is the process
by which individual cells process nutrient molecules. Metabolism
has two distinct divisions; catabolism, in which the cell breaks
down complex molecules to produce energy and reducing power, and
anabolism, where the cell uses energy and reducing power to
construct complex molecules and perform other biological functions.
Complex sugars consumed by the organism can be broken down into a
less chemically complex sugar molecule called glucose. Once inside
the cell, glucose is broken down to make adenosine triphosphate
(ATP), a form of energy, via two different pathways.
The first pathway, glycolysis, requires no oxygen and is
referred to as anaerobic metabolism. Each reaction is designed to
produce some hydrogen ions that can then be used to make energy
packets (ATP). In prokaryotes, glycolysis is the only method used
for converting energy. The second pathway, called the Kreb's cycle,
or citric acid cycle, occurs inside the mitochondria and is capable
of generating enough ATP to run all the cell functions.
Making new cells
Cell division involves a single cell (called a mother cell)
dividing into two daughter cells. This leads to growth in
multicellular organisms (the growth of tissue) and to procreation
(vegetative reproduction) in unicellular organisms. Eukaryotic
cells usually undergo a process of nuclear division, called
mitosis, followed by division of the cell, called cytokinesis. A
diploid cell may also undergo meiosis to produce haploid cells,
usually four. Haploid cells serve as gametes in multicellular
organisms, fusing to form new diploid cells. DNA replication, or
the process of duplicating a cell's genome, is required every time
a cell divides. Replication, like all cellular activities, requires
specialized proteins for carrying out the job.
Protein synthesis
Protein synthesis is the process in which the cell builds
proteins. DNA transcription refers to the synthesis of a messenger
RNA (mRNA) molecule from a DNA template. This process is very
similar to DNA replication. Once the mRNA has been generated, a new
protein molecule is synthesized via the process of translation.
The cellular machinery responsible for synthesizing proteins is
the ribosome. The ribosome consists of structural RNA and about 80
different proteins. When the ribosome encounters an mRNA, the
process of translating an mRNA to a protein begins. The ribosome
accepts a new transfer RNA, or tRNAthe adaptor molecule that acts
as a translator between mRNA and proteinbearing an amino acid, the
building block of the protein. Another site binds the tRNA that
becomes attached to the growing chain of amino acids, forming the a
polypeptide chain that will eventually be processed to become a
protein.
Origins of cells
The origin of cells has to do with the origin of life, and was
one of the most important steps in evolution of life as we know it.
The birth of the cell marked the passage from prebiotic chemistry
to biological life. If life is viewed from the point of view of
replicators, that is DNA molecules in the organism, cells satisfy
two fundamental conditions: protection from the outside environment
and confinement of biochemical activity. The former condition is
needed to maintain the fragile DNA chains stable in a varying and
sometimes aggressive environment, and may have been the main reason
for which cells evolved. The latter is fundamental for the
evolution of biological complexity . If freely-floating DNA
molecules that code for enzymes that are not enclosed into cells,
the enzymes that advantage a given DNA molecule (for example, by
producing nucleotides) will automatically advantage the
neighbouring DNA molecules. This might be viewed as "parasitism by
default". Therefore the selection pressure on DNA molecules will be
much lower, since there is not a definitive advantage for the
"lucky" DNA molecule that produces the better enzyme over the
others: all molecules in a given neighbourhood are almost equally
advantaged. If all the DNA molecule is enclosed in a cell, then the
enzymes coded from the molecule will be kept close to the DNA
molecule itself. The DNA molecule will directly enjoy the benefits
of the enzymes it codes, and not of others. This means other DNA
molecules won't benefit from a positive mutation in a neighbouring
molecule: this means that positive mutations give immediate and
selective advantage to the replicator bearing it, and not on
others. This is thought to have been the one of the main driving
force of evolution of life as we know it. (Note. This is more a
metaphor given for simplicity than complete accuracy, since the
earliest molecules of life, probably up to the stage of cellular
life, were most likely RNA molecules, acting both as replicators
and enzymes: see RNA world hypothesis . But the core of the
reasoning is the same.)
Biochemically, cell-like spheroids formed by proteinoids are
observed by heating amino acids with phosphoric acid as a catalyst.
They bear much of the basic features provided by cell membranes.
Proteinoid-based protocells enclosing RNA molecules could (but not
necessarily should) have been the first cellular life forms on
Earth.
Origin of eukaryotic cells
The eukaryotic cell seems to have evolved from a symbiotic
community of prokaryotic cells. It is almost certain that
DNA-bearing organelles like the mitochondria and the chloroplasts
are what remains of ancient symbiotic oxygen-breathing bacteria and
cyanobacteria, respectively, where the rest of the cell seems to be
derived from an ancestral archaean prokaryote cell a theory termed
the endosymbiotic theory.
There is still considerable debate on if organelles like the
hydrogenosome predated the origin of mitochondria, or viceversa:
see the hydrogen hypothesis for the origin of eukaryotic cells.
History
1632-1723: Antony van Leeuwenhoek teaches himself to grind
lenses, builds a microscope and draws protozoa, such as Vorticella
from rain water, and bacteria from his own mouth.
1665: Robert Hooke discovers cells in cork, then in living plant
tissue using an early microscope.
...I could exceedingly plainly perceive it to be all perforated
and porous, much like a Honeycomb...these pores or cells, were not
very deep, but consisted of a great many little boxes... Hooke
describing his observations on a thin slice of cork.
1839: Theodor Schwann and Matthias Jakob Schleiden elucidate the
principal that plants and animals are made of cells, concluding
that cells are a common unit of structure and development, thus
founding the Cell Theory.
The belief that life forms are able to occur spontaneously
(generatio spontanea) is contradicted by Louis Pasteur
(1822-1895).
Rudolph Virchow states that cells always emerge from cell
divisions (omnis cellula ex cellula).
1931: Ernst Ruska builds first transmission electron microscope
(TEM) at the University of Berlin. By 1935 he has built an EM with
twice the resolution of a light microscope, revealing previously
unresolvable organelles.
1953: Watson and Crick made their first announcement on the
double-helix structure for DNA on February 28.
1981: Lynn Margulis published Symbiosis in Cell Evolution
detailing the endosymbiotic theory.
Cell membrane
The selectively permeable cell membrane (or plasma membrane or
plasmalemma) is a thin and structured bilayer of phospholipid and
protein molecules that envelopes the cell. It separates a cell's
interior from its surroundings and controls what moves in and out.
Cell surface membranes often contain receptor proteins and cell
adhesion proteins. There are also other proteins with a variety of
functions. These membrane proteins are important for the regulation
of cell behavior and the organization of cells in tissues.
Transmembrane receptorTransmembrane receptors are integral
membrane proteins, which reside and operate typically within a
cell's plasma membrane, but also in the membranes of some
subcellular compartments and organelles. Binding to a signalling
molecule or sometimes to a pair of such molecules on one side of
the membrane, transmembrane receptors initiate a response on the
other side. In this way they play a unique and important role in
cellular communications and signal transduction.
Many transmembrane receptors are composed of two or more protein
subunits which operate collectively and may dissociate when ligands
bind, fall off, or at another stage of their "activation" cycles.
They are often classified based on their molecular structure, or
because the structure is unknown in any detail for all but a few
receptors, based on their hypothesized (and sometimes
experimentally verified) membrane topology. The polypeptide chains
of the simplest are predicted to cross the lipid bilayer only once,
while others cross as many as seven times (the so-called G-protein
coupled receptors).
Like any integral membrane protein, a transmembrane receptor may
be subdivided into three parts or domains.
E=extracellular space; I=intracellular space; P=plasma
membrane
The extracellular domain
The extracellular domain is the part of the receptor that sticks
out of the membrane on the outside of the cell or organelle. If the
polypeptide chain of the receptor crosses the bilayer several
times, the external domain can comprise several "loops" sticking
out of the membrane. By definition. a receptor's main function is
to recognize and respond to a specific ligand, for example, a
neurotransmitter or hormone (although certain receptors respond
also to changes in transmembrane potential), and in many receptors
these ligands bind to the extracellular domain.
The transmembrane domain
In the majority of receptors for which structural evidence
exists, transmembrane alpha helices make up most of the
transmembrane domain. In certain receptors, such as the nicotinic
acetylcholine receptor, the transmembrane domain forms a
protein-lined pore through the membrane, or ion channel. Upon
activation of an extracellular domain by binding of the appropriate
ligand, the pore becomes accessible to ions, which then pass
through. In other receptors, the transmembrane domains are presumed
to undergo a conformational change upon binding, which exerts an
effect intracellularly. In some receptors, such as members of the
7TM superfamily, the transmembrane domain may contain the ligand
binding pocket (evidence for this and for much of what else is
known about this class of receptors is based in part on studies of
bacteriorhodopsin, the detailed structure of which has been
determined by crystallography).
The intracellular domain
The intracellular (or cytoplasmic) domain of the receptor
interacts with the interior of the cell or organelle, relaying the
signal. There are two fundamentally different ways for this
interaction:
The intracellular domain communicates via specific
protein-protein-interactions with effector proteins, which in turn
send the signal along a signal chain to its destination.
The intracellular domain has enzymatic activity. Often, this is
a tyrosine kinase activity. The enzymatic activity can also be
located on an enzyme associated with the intracellular domain.
Regulation of receptor activity
There are several ways for the cell to regulate the activity of
a transmembrane receptor. Most of them work through the
intracellular domain. The most important ways are phosphorylation
and internalization (see ubiquitin).
Phosphorylation is the addition of a phosphate (PO4) group to a
protein or a small molecule. Its prominent role in biochemistry is
the subject of a very large body of research (the Medline database
returns over 100,000 articles on the subject, largely on protein
phosphorylation).
Protein phosphorylation
Function
Protein phosphorylation is probably the most important
regulatory event. Many enzymes and receptors are switched "on" or
"off" by phosphorylation and dephosphorylation. Phosphorylation is
catalyzed by various specific protein kinases, whereas phosphatases
dephosphorylate.
An example of the important role that phosphorylation plays is
the p53 tumor suppressor gene, whichwhen activestimulates
transcription of gene that suppress the cell cycle, even to the
extent that it undergoes apoptosis. However, this activity should
be limited to situations where the cell is damaged or physiology is
disturbed. To this end, the p53 protein is extensively regulated.
In fact, p53 contains more than 18 different phosphorylation
sites.
Upon the deactivating signal, the protein becomes
dephosphorylated again and stops working. This is the mechanism in
many forms of signal transduction, for example the way in which
incoming light is processed in the light-sensitive cells of the
retina.
Signaling networks
The network underlying phosphorylation can be very complex. In
some cellular signalling pathways, a protein A phosphorylates B,
and B phosphorylates C, but A also phosphorylates C directly, and B
can phosphorylate D, which may in turn phosphorylate A.
Types of phosphorylation
Within a protein, phosphorylation can occur on several amino
acids. Phosphorylation on serine is the most common, followed by
threonine. Tyrosine phosphorylation is relatively rare. However,
since tyrosine phosphorylated proteins are relatively easy to
purify using antibodies, tyrosine phosphorylation sites are
relatively well understood.
A protein kinase is an enzyme that can transfer a phosphate
group from a donor molecule (usually ATP) to an amino acid residue
of a protein. The protein kinase mechanism is used in signal
transduction for the regulation of enzymes: phosphorylation can
activate (or inhibit) the activity of an enzyme. Although most
protein kinases are specialized for a single kind of amino acid
residue, some exhibit dual kinase activity (they can phosphorylate
two different kinds of amino acids).Other kinds ATP, the
"high-energy" exchange medium in the cell, is synthesized in the
mitochondrion by addition of a third phosphate group to ADP in a
process referred to as oxidative phosphorylation. ATP is also
synthesized by substrate level phosphorylation during glycolysis.
Phosphorylation of sugars is often the stage of their catabolism.
It allows cells to accumulate sugars because the phosphate group
prevents the molecules from diffusing back across their
transporter.
A tyrosine kinase is an enzyme that can transfer a phosphate
group to a tyrosine residue in a protein; these enzymes are a
subgroup of the larger class of protein kinases. Phosphorylation is
an important function in signal transduction to regulate enzyme
activity. The hormones that act on tyrosine kinase receptors are
generally growth hormones and factors that promote cell division
(e.g., insulin, insulin-like growth factor 1, epidermal-derived
growth factor).
A Fluid Mosaic
The basic composition and structure of the plasma membrane is
the same as that of the membranes that surround organelles and
other subcellular compartments. The foundation is a phospholipid
bilayer, and the membrane as a whole is often described as a 'fluid
mosaic' - a two-dimensional fluid of freely diffusing lipids,
dotted or embedded with proteins which may function as channels or
transporters across the membrane, or as receptors. Some of these
proteins simply adhere to the membrane (extrinsic or peripheral
proteins), while others might be said to reside within it or to
span it (intrinsic proteins -- more at integral membrane protein).
Glycoproteins have carbohydrates attached to their extracellular
domains. Cells may vary the variety and the relative amounts of
different lipids to maintain the fluidity of their membranes
despite changes in temperature. Cholesterol molecules (in case of
eukaryotes) or hopanoids (in case of prokaryotes) in the bilayer
assist in regulating fluidity.
Phospholipids are formed from four components: fatty acids, a
negatively charged phosphate group, an alcohol and a backbone.
Phospholipids with a glycerol backbone are known as
phosphoglycerides. There is only one type of phospholipid with a
sphingosine backbone; sphingomyelin. Phospholipids are a major
component of all biological membranes, along with glycolipids and
cholesterol.
Detailed Structure
In fact, not all lipid molecules in the cell membrane are
"fluid," in the sense of free to diffuse. Lipid rafts and caveolae
are examples of more cohesive membrane regions. Across the membrane
globally, also many proteins are not entirely free to diffuse. The
cytoskeleton undergirds the cell membrane and provides anchoring
points for integral membrane proteins. Anchoring restricts them to
a particular cell face or surface--for example, the "apical"
surface of epithelial cells that line the vertebrate gut--and
limits how far they may diffuse within the bilayer. Finally, rather
than presenting always a formless and fluid contour, the plasma
membrane surface of cells may show structure. Returning to the
example of epithelial cells in the gut, the apical surfaces of many
such cells are dense with involutions, all similar in size. The
finger-like projections, called "microvilli", increase cell surface
area and facilitate the absorption of molecules from the outside.
Synapses are another example of highly structured membrane.
Transport across membranes
As a lipid bilayer, the cell membrane is selectively permeable.
This means that only some molecules can pass unhindered in or out
of the cell. These molecules are either small or lipophilic. Other
molecules can pass in or out of the cell, if there are specific
transport molecules.
Depending on the molecule, transport occurs by different
mechanisms, which can be separated into those that do not consume
energy in the form of ATP (passive transport) and those that do
(active transport):
Passive transport
Passive transport is a means of moving biochemicals, and other
atomic or molecular substances, across membranes. Unlike active
transport, this process does not involve chemical energy (ATP).
Passive transport is dependent on the permeability of the cell
membrane, which, in turn, is dependent on the organization and
characteristics of the membrane lipids and proteins. The four main
kind of passive transport are diffusion, facilitated diffusion,
filtration and osmosis.
Diffusion
Diffusion is the net movement of material from an area of high
concentration of that material to an area with lower concentration.
The difference of concentration between the two areas is often
termed as the concentration gradient, and diffusion will continue
until this gradient has been eliminated. Since diffusion moves
material from area of higher concentration to the lower, it is
described as moving solutes "down the concentration gradient"
(compared with active transport, which often moves material from
area of low concentration to area of higher concentration, and
therefore referred to as moving the material "against the
concentration gradient").
If and when the concentration gradient have been eliminated, no
net exchange of material occurs. Although material may move forth
from one area to the other, it will be balanced by movement of the
same amount of material to the opposite direction.
Diffusion is biologically important because it enables the
abolishment of concentration gradients in the body. For example,
metabolic activity will consume oxygen, which will reduce its
concentration in the bloodstream; diffusion of oxygen in the
alveoli of the lungs allows it to be replenished.
Facilitated diffusion
Facilitated diffusion is movement of molecules across the cell
membrane via special carrier proteins that are embedded within the
cellular membrane. A lot of large molecules, such as glucose, are
insoluble in lipids and too large to fit through the membrane
pores. Therefore, it will bind with its specific carrier proteins,
and the complex will then be bonded to a receptor site and moved
through the cellular membrane. Bear in mind, however, that
facilitated diffusion is a passive process, and the solutes still
move down the concentration gradient.
Filtration
Filtration is movement of water and solute molecules across the
cell membrane due to hydrostatic pressure generated by the
cardiovascular system. Depending on the size of the membrane pores,
only solutes of a certain size may pass through it. For example,
the membrane pores of the Bowman's capsule in the kidneys are very
small, and only albumin, the smallest of the proteins, have any
chance of being filtered through. On the other hand, the membrane
pores of liver cells are extremely large, to allow a veriety of
solutes to pass through and be metabolized.
Osmosis
Osmosis is basically diffusion of water molecules. Most cell
membranes are permeable to water, and since the diffusion of water
plays such an important role in the biological functioning of any
living being, a special term has been coined for it -- osmosis.
Water molecules "stick" together via weak hydrogen bonds;
therefore, unlike most solutes, water molecules move around in
large clumps, a phenomenon known as bulk flow.
Categories: Cell biology | Biochemistry | PhysiologyActive
transport
Typically moves molecules against their electrochemical gradient
, a process that would be entropically unfavorable were it not
stoichiometrically coupled with the hydrolysis of ATP. This
coupling can be either primary or secondary. In the primary active
transport, transporters that move molecules against their
electrical/chemical gradient, hydrolyze ATP. In the secondary
active transport, transporters use energy derived from transport of
another molecule in the direction of their gradient, to move other
molecules in the direction against their gradient. This can be
either symport (in the same direction) or antiport (in the opposite
direction).
Examples include:
1. endocytosis
2. exocytosis, in which molecules packaged in membrane vesicles
are either imported or exported, respectively. Molecular exchangers
, transporters and pumps represent other examples.
Active transport is the mediated transport of biochemicals, and
other atomic/molecular substances, across membranes. Unlike passive
transport, this process requires chemical energy. In this form of
transport, molecules move against either an electrical or
concentration gradient (collectively termed an electrochemical
gradient). This is achieved by either altering the affinity of the
binding site or altering the rate at which the protein changes
conformations.
Types
There are two main types, primary and secondary. In primary
transport energy is directly coupled to movement of desired
substance across a membrane, independent of any other species.
Secondary transport concerns the diffusion of one species across a
membrane to drive the transport of another.
Primary
Primary active transport directly uses energy to transport
molecules across a membrane. Most of the enzymes that perform this
type of transport are transmembrane ATPases. A primary ATPase
universal to all cellular life is the sodium-potassium pump, which
helps maintain the cell potential.
ATPases are a class of enzymes that catalyze the decomposition
of adenosine triphosphate (ATP) into adenosine diphosphate (ADP)
and a free phosphate ion. This dephosphorylation reaction releases
energy, which the enzyme (in most cases) harnesses to drive other
chemical reactions that would not otherwise occur. Some such
enzymes are integral membrane proteins (anchored within biological
membranes), and move solutes across the membrane. (These are called
transmembrane ATPases).
Transmembrane ATPases import many of the metabolites necessary
for cell metabolism and export toxins, wastes, and solutes that can
hinder cellular processes. An important example is the
sodium-potassium exchanger (or Na+/K+ATPase), which establishes the
ionic concentration balance that maintains the cell potential.
Secondary
In secondary active transport, there is no direct coupling of
ATP; instead, the electrochemical potential difference created by
pumping ions out of cells is used. The two main forms of this are
counter-transport (antiport) and co-transport (symport).
Counter-transport
In counter-transport two species of ion or other solute are
pumped in opposite directions across a membrane. One of these
species is allowed to flow from high to low concentration, which
yields the entropic energy to drive the transport of the other
solute from a low concentration region to a high one. An example is
the sodium-calcium exchanger or antiporter, which allows three
sodium ions into the cell to transport one calcium out.
Many cells also posses a calcium ATPase, which can operate at
lower intracellular concentrations of calcium and sets the normal
or resting concentration of this important second messenger. But
the ATPase exports calcium ions more slowly: only 30 per second
versus 2000 per second by the exchanger. The exchanger comes into
service when the calcium concentration rises steeply or "spikes"
and enables rapid recovery. This shows that a single type of ion
can be transported by several enzymes, which need not be active all
the time (constitutively), but may exist to meet specific,
intermittent needs.
Co-transport
Co-transport also uses the flow of one solute species from high
to low concentration to move another molecule against its preferred
direction of flow; but here, both solutes move in the same
direction across the membrane. An example is the glucose symporter,
which cotransports two sodiums for every molecule of glucose it
imports into the cell.
Movement of proteins
Proteins are synthesized by ribosomes in the cytoplasm. This
process is also known as protein biosynthesis or simply protein
translation. Some proteins, such as those to be incorporated in
membranes (membrane proteins), are transported into the ER during
synthesis and further processed in the Golgi apparatus. From the
Golgi, membrane proteins can move to the plasma membrane, to other
subcellular comparments or they can be secreted from the cell. The
ER and Golgi can be thought of as the "membrane protein synthesis
compartment" and the "membrane protein processing compartment",
respectively. There is a constant flux of proteins through these
compartments. ER and Golgi-resident proteins associate with other
proteins and remain in their respective compartments. Other
proteins "flow" through the ER and Golgi to the plasma membrane.
From the plasma membrane, proteins destined to be degraded move
back into intracellular compartments where they are broken down to
their individual amino acids.
Summary of the different methods by which molecules can enter
cells.
Cell adhesion
Schematic of cell adhesion
Cells are often not found in isolation, rather they tend to
stick to other cells or non-cellular components of their
environment. A fundamental question is: what makes cells sticky?
Cell adhesion generally involves protein molecules at the surface
of cells, so the study of cell adhesion involves cell adhesion
proteins and the molecules that they bind to.
Cell adhesion proteins (or Cell adhesion molecules, CAMs)
Cell adhesion proteins are often transmembrane receptors.
Transmembrane cell adhesion proteins extend across the cell surface
membrane and typically have domains that extend into both the
extracellular space and the intracellular space. The extracellular
domain of a cell adhesion protein can bind to other molecules that
might be either on the surface of an adjacent cell (cell-to-cell
adhesion) or part of the extracellular matrix (cell-to-ECM
adhesion). The molecule that a cell adhesion protein binds to is
called its ligand. There are families of cell adhesion proteins
that can be characterized in terms of the structure of the adhesion
proteins and their ligands. Adhesion between two copies of the same
adhesion protein is called "homophilic" binding. Adhesion between
an adhesion protein and some other molecule is "heterophilic"
binding.
Major Cell Adhesion Protein Families
Familyligandsinteractions
Selectins Carbohydratesheterophilic
Integrins Extracellular matrixheterophilic
Ig superfamily proteinsheterophilic
Ig superfamily proteins Integrinsheterophilic
Ig superfamily proteinshomophilic
Cadherins Cadherinshomophilic
Cytoskeletal interactionsFor a cell adhesion protein like the
one shown in the diagram, the intracellular domain binds to protein
components of the cell's cytoskeleton. This allows for very tight
adhesion. Without attachment to the cytoskeleton, a cell adhesion
protein that is tightly bound to a ligand would be in danger of
being ripped out of the fragile cell membrane. Often the connection
between the cell adhesion proteins and the cytoskeleton is not as
direct as shown in the diagram. For example, cadherin cell adhesion
proteins are typically coupled to the cytoskeleton by way of
special linking proteins called "catenins".
Importance of cell adhesionCell adhesion proteins are important
for the normal functioning of living organisms. Cell adhesion
proteins hold together the components of solid tissues. They are
also important for the function of migratory cells like white blood
cells. Regulation of cell adhesion proteins is important during
embryonic development for the process of morphogenesis. Some people
have "blistering diseases" that result from inherited molecular
defects in genes for adhesion proteins. Some cancers involve
mutations in genes for adhesion proteins that result in abnormal
cell-to-cell interactions and tumor growth. Cell adhesion proteins
are also important for interactions that allow viruses and bacteria
to cause damage to humans. Cell adhesion proteins hold synapses
together and the regulation of synaptic adhesion is involved in
learning and memory. In Alzheimer's disease there is abnormal
regulation of synaptic cell adhesion.
Desmosome
Cell adhesion in desmosomes
A desmosome (also known as macula adherens) is a cell structure
specialized for cell-to-cell adhesion. Desmosomes are molecular
complexes of cell adhesion proteins and linking proteins that
attach the cell surface adhesion proteins to intracellular keratin
cytoskeletal filaments. The cell adhesion proteins of the desmosome
are members of the cadherin family of cell adhesion molecules. They
are transmembrane proteins that bridge the space between adjacent
epithelial cells by way of homophilic binding of their
extracellular domains to other desmosomal cadherins on the adjacent
cell. The desmosomal linking proteins such as desmoplakin bind to
the intracellular domain of cadherins and form a connecting bridge
to the cytoskeleton.
Blistering diseases
If the desmosomes connecting adjacent epithelial cells of the
skin are not functioning correctly, layers of the skin can pull
apart and allow abnormal movements of fluid within the skin,
resulting in blisters and other tissue damage. Blistering diseases
such as Pemphigus Vulgaris can be due to genetic defects in
desmosomal proteins or due to an autoimmune response. These
patients are often be found to have antibodies that bind to the
desmosomal cadherins and disrupt the desmosomes.
Hemidesmosomes
When visualized by electron microscopy, hemidesmosomes are
similar in appearance to desmosomes. Rather than linking two cells,
hemidesmosomes attach one cell to the extracellular matrix. Rather
than using cadherins, hemidesmosomes use integrin cell adhesion
proteins.
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton"
contained within the cytoplasm. It is a dynamic structure that
maintains cell shape, enables some cell motion (using structures
such as flagella and cilia), and plays important roles in both
intra-cellular transport (the movement of vesicles and organelles,
for example) and cellular division. Eukaryotic cells contain three
kinds of cytoskeletal filaments.
Actin Filaments
Actin is a globular protein that polymerize helicaly forming
actin filaments (or microfilaments), which like the other two
components of the cellular cytoskeleton form a three-dimensional
network inside an eukariotic cell. Actin filaments provide
mechanical support for the cell, determine the cell shape, enable
cell movements (through pseudopods); and participate in certain
cell junctions, in cytoplasmic streaming and in contraction of the
cell during cytokinesis. In muscle cells they play an essential
role, along with myosin, in muscle contraction. In the cytosol,
actin is predominantly bound to ATP, but can also bind to ADP. An
ATP-actin complex polymerizes faster and dissociates slower than an
ADP-actin complex. Actin is also one of the most highly conserved
proteins, differing by no more than 5% in species as diverse as
algae and humans.
Microfilaments assembly
The globular Actin is known as G-actin, while the filamentous
polymer composed of G-actin subunits (a microfilament), is called
F-actin. The microfilaments are the thickest of the cytoskeleton,
with only 7nm in diameter. Much like the microtubules, actin
filaments are polar, with the plus (+) end elongating approximately
10 times faster than the minus (-) end. The process of actin
polymerization, nucleation, starts with the association of three
G-actin monomers into a trimer. ATP-actin then binds the plus (+)
end, and the ATP is subsequently hydrolyzed, which reduces the
binding strength between neighboring units and generally
destabilizes the filament. ADP-actin dissociates from the minus end
and the increase in ADP-actin stimulates the exchange of bound ADP
for ATP, leading to more ATP-actin units. This rapid turnover is
important for the cells movement.
The protein cofilin binds to ADP-actin units and promotes their
dissociation from the minus end and prevents their reassembly. The
protein profilin reverses this effect by stimulating the exchange
of bound ADP for ATP. In addition, ATP-actin units bound to
profilin will dissociate from cofilin and are then free to
polymerize. Another important component in filament production is
the Arp2/3 proteins, which serve as sites for nucleation,
stimulating the formation of G-actin trimers. All of these three
proteins are regulated by cell signaling mechanism.
Actin filaments are assembled in two general types of
structures: bundles and networks. Actin-binding proteins dictate
the formation of either structure since they cross-link actin
filaments. Actin filaments have the appearance of a double-stranded
helix.
Bundles
There are two types of actin bundles: parallel and contractile
bundles. In parallel bundles, the filaments are spaced 14nm apart
by the actin-bundling proteins fimbrin. Parallel bundles are
responsible for the supporting a cells microvilli. In vertebrates,
the actin-bundling protein villin is almost entirely found in the
microvilli of intestinal cells.
Together with myosin filaments actin it forms Actomyosin, which
provides the mechanism for muscle contraction. Actin uses ATP for
energy. The ATP allows, through hydrolysis, the myosin head to
extend up and bind with the actin filament. The myosin head then
releases after moving the actin filament in a relaxing or
contracting movement by usage of ADP.
In contractile bundles, the actin-bundling protein actinin
separates each filament by 40nm. This increase in distance allows
the motor protein myosin to interact with the filament, enabling
deformation or contraction. In the first case, one end of myosin is
bound to the plasma membrane while the other end walks towards the
plus end of the actin filament. This pulls the membrane into a
different shape relative to the cell cortex. For contraction, the
myosin molecule is usually bound to two separate filaments and both
ends simultaneously walk towards their filament's plus end, sliding
the actin filaments over each other. This results in the
shorterning, or contraction, of the actin bundle (but not the
filament). This mechanism is responsible for muscle contraction and
cytokinesis, the division of one cell into two.
Networks
Actin networks, along with their actin-binding protein, filamin
, form the cells cortex. This underlies the plasma membrane and is
responsible for the shape of the cell.
Intermediate Filaments
These 8 to 11 nanometers in diameter filaments are the more
stable (strongly bound) and heterogenous constitutents of the
cytoskeleton. They organize the internal tridimensional structure
of the cell (they are structural components of the nuclear envelope
or the sarcomeres for example). Their size is intermediate between
that of microfilaments and microtubules. They are assembled from
several different proteins. IFs crisscross the cytosol from the
nuclear envelope to the cell membrane. They also participate in
some cell-cell and cell-matrix junctions.
Different intermediate filaments are:
vimentins, being the common structural support of many
cells.
keratin, found in skin cells, hair and nails.
Neurofilaments of neural cells.
Lamin, giving structural support to the nuclear envelope.
Microtubules
They are hollow cylinders of about 25 nm., formed by 13
protofilaments which, in turn, are polymers of alpha and beta
tubulin (a potein). They have a very dynamic behaviour, binding GTP
for polymerization, they are organized by the centrosome.
They play key roles in:
Intracellular transport (asociated with dyneins and kinesins
they transport organelles like mitochondria or vesicles.)
the axoneme of cilia and flagella
the mitotic spindle
Microtubules are part of a structural network (the cytoskeleton)
within the cell's cytoplasm, but in addition to structural support
microtubules are used in many other processes as well. They are
capable of growing and shrinking in order to generate force, and
there are also motor proteins that move along the microtubule. A
notable structure involving microtubules is the mitotic spindle
used by eukaryotic cells to segregate their chromosomes correctly
during cell division. Microtubules are also responsible for the
flagella of eukaryotic cells (prokaryote flagella are entirely
different).
Dynamic Instability
Tubulin binds GTP in order to assemble onto the (+) end of a
microtubule. Shortly after assembly, the GTP is hydrolyzed to GDP.
A GDP-bound tubulin subunit at the tip of a microtubule will fall
off, though a GDP-bound tubulin in the middle of a microtubule
cannot spontaneously pop out. Since tubulin adds onto the end of
the microtubule only in the GTP-bound state, there is generally a
cap of GTP-bound tubulin at the tip of the microtubule, protecting
it from disassembly. When hydrolysis catches up to the tip of the
microtubule, it begins a rapid depolymerization and shrinkage. This
switch from growth to shrinking is called a catastrophe. GTP-bound
tubulin can begin adding to the tip of the microtubule again,
providing a new cap and protecting the microtubule from shrinking.
This is referred to as rescue.
The drug taxol, used in the treatment of cancer, blocks dynamic
instability by stabilizing GDP-bound tubulin in the microtubule.
Thus, even when hydrolysis of GTP reaches the tip of the
microtubule, there is no depolymerization and the microtubule does
not shrink back. Colchicine has the opposite effect: it blocks the
polymerization of tubulin into microtubules.
Motor Proteins
In addition to movement generated by the dynamic instability of
the microtubule itself, the fibers are substrates along which motor
proteins can move. The major microtubule motor proteins are kinesin
and dynein.
Cilium
A cilium (plural cilia) is a fine projection from a cell. There
are two types of cilia: (1) motile cilium, which constantly beats
in one direction, and (2) non-motile cilium, which cannot beat and
usually serves as a sensor.
Cilia are structurally identical to eukaryotic flagella, and the
two terms are often used interchangeably. In general, though, the
term cilia is used when they are numerous, short and coordinated
while flagella is used when they are relatively sparse and long.
The name cilium may also be used to emphasize their differences
from bacterial flagella.
Motile cilia are almost never found alone, usually being present
on a cell's surface in large numbers that beat coordinately in
unified waves. In humans, for example, motile cilia are found in
the lining of the trachea or windpipe, where they sweep mucus and
dirt out of the lungs. In the oviducts, the beating of cilia moves
the ovum from the ovary to the uterus.
Opposite to the motile cilia, non-motile cilium usually exists
as one cilium per cell. The outer segment of the rod photoreceptor
cell in the human eye is connected to its cell body with a
specialized non-motile cilium. The terminal fiber of the olfactory
neuron is also a non-motile cilium, where the odorant receptors
locate. Almost all types of the mammalian cells have a single
non-motile cilium called "Primary cilium" that has been neglected
for a long time. Recent studies led scientists to re-evaluate its
physiological role(s) in the cell signaling and the control of cell
growth and development.
A cilium has an outer membrane that surrounds a core called an
axoneme, which contains nine pairs of microtubule doublets and
other associated proteins. Motile cilia have a central core with
two additional microtubule singlets and dynein motor proteins which
are attached to the outer microtubule doublets. Biologists refer to
this organization as a cononical "9 + 2" structure. The non-motile
cilia do not have the two central microtubule singlets and do not
have dyneins. This configuration of axoneme is referred as a "9 +
0" type. At the base of the cilium is its microtubule organization
center called a basal body. Basal body is structurally identical to
and functionally interchangeable with centriole in the animal
cells. The region between the basal body and axoneme is a short
transition zone which is less studied.
A defect in the cilium can cause human disease. The best known
cilia-related disorder is Primary Ciliary Dyskinesia (PCD). In
addition, a defect of the primary cilium in the renal tube cells
can lead to polycystic kidney disease (PKD). In another genetic
disorder called Bardet-Biedl syndrome (BBS), the mutant gene
products are the components in the basal body and cilia.
Dynein
Dynein is a class of protein and can be divided into two groups:
cytoplasmic dynein and axonemal dynein. The axonemal dynein acts to
activate a sliding within flagellar microtubules, whereas the
cytoplasmic dynein is implicated in moving toward the negative end
of a microtubule.
Kinesin
Kinesins typically consist of two large globular heads that
allow attachment to microtubules, a central coiled region, and a
region termed light-chain, which connects the kinesin to the
intracellular component to be moved.
Kinesin and Dynein belong to Microtubule Associated Proteins
(MAPs). These motor MAPs attach both to intracellular components,
and to microtubles (MTs), and by moving along the MT they are able
to transport the intracellular components, which could be
organelles, or vesicles, to where they are required.
Cytoplasm
Cytoplasm is the colloidal, semi-fluid matter contained within
the cell's plasma membrane, in which organelles are suspended. In
contrast to the protoplasm, the cytoplasm does not include the cell
nucleus, the interior of which is made up of nucleoplasm.
Components of the cytoplasm
The aqueous component of the cytoplasm (making up 80 percent of
it) is composed of ions and soluble macromolecules like enzymes,
carbohydrates, different salts and proteins, as well as a great
proportion of ARN. The cytoplasm's watery component is also known
as hyaloplasm .
The watery component can be more or less gel-like or liquid
depending on the milieu's conditions and the activity phases of the
cell. In the first case, it is named cytogel and is a viscid solid
mass. In the second case, called cytosol, is a liquid in movement.
In general, margin regions of the cell are gel-like and the cell's
interior is liquid.
The insoluble constituents of the cytoplasm are organelles (such
as the mitochondria, the lysosomes HYPERLINK
"http://www.biologydaily.com/biology/Chloroplast"
, peroxysomes, ribosomes), several vacuoles, cytoskeletons as
well as complex membrane structures (e.g. endoplasmic reticulums or
the golgi apparatus).
Function
The cytoplasm plays a mechanical role, i.e. to maintain the
shape, the consistency of the cell and to provide suspension to the
organelles. It is also a storage place for chemical substances
indispensable to life. Vital metabolic reactions take place here,
for example anaerobic glycolysis and proteic synthesis.
Cytosol
The cytosol (as opposed to cytoplasm, which also includes the
organelles) is the internal fluid of the cell, and a large part of
cell metabolism occurs here. Proteins within the cytosol play an
important role in signal transduction pathways, glycolysis, and
they act as intracellular receptors and ribosomes. In prokaryotes,
all chemical reactions take place in the cytosol. In eukaryotes,
the cytosol contains the cell organelles. The cytosol is not a
"soup" with free-floating particles, but is highly organized on the
molecular level. The cytosol also contains the cytoskeleton. This
is made of fibrous proteins (microfilaments, microtubules, and
intermediate filaments) and (in many organisms) maintains the shape
of the cell, anchors organelles, and controls internal movement of
structures, e.g., transport vesicles.
As the concentration of soluble molecules increases within the
cytosol, an osmotic gradient builds up toward the outside of the
cell. Water flows into the cell, making the cell larger. To prevent
the cell from bursting apart, molecular pumps in the plasma
membrane, the cytoskeleton, the tonoplast or the cell wall (if
present), are used to counteract the osmotic pressure. Details
The cytosol is 20% to 30% protein.
Normal human cytosolic pH is (roughly) 7.0 (i.e. neutral),
whereas the pH of the extracellular fluid is 7.4.
Vesicle
A vesicle is a relatively small and enclosed compartment,
separated from the cytosol by at least one lipid bilayer. Vesicles
store, transport, or digest cellular products and wastes.
This biomembrane enclosing the vesicle is the same as that of
the outer (cellular) membrane. Thus, because of the separation, the
intravesicular environment can be made to be different from the
cytosolic environment. Vesicles are a basic tool of the cell for
organizing metabolism, transport, enzyme storage, as well as being
chemical reaction chambers. Many vesicles are made in the Golgi
apparatus, but also in the endoplasmic reticulum, or are made from
parts of the plasma membrane.
Lysosomes (membrane-bound digestive vesicles) can digest
macromolecules (break them down to small compounds) that were taken
in from the outside of the cell by an endocytic vesicle. This is
the basic way for a cell to feed (except for photosynthesis in
plants, which don't have lysosomes). The membrane of the lysosome
is impermeable for lysozyme, the enzyme that does the actual
digestion, to protect the cell interior from being digested by its
own enzyme. Lysosomes are made in the Golgi apparatus.
Neurons store neurotransmitters in synaptic vesicles located at
presynaptic terminals.
Transport vesicles
Transport vesicles can move molecules between locations inside
the cell, e.g., proteins from the endoplasmic reticulum to the
Golgi apparatus, and from there to the outer cell membrane, where
they are secreted. They do this by budding off from one compartment
and joining to another. Anterograde transport vesicles : These are
forward-moving vesicles.
Retrograde transport vesicles : These vesicles move from later
to earlier cisterna.
Vesicles can be used as reaction chambers for chemical reactions
that could damage the cell if they would occur in the cytosol. For
example, peroxisomes are detoxifiers of hydrogen peroxide (H2O2), a
toxic byproduct of cell metabolism. Large storage vesicles are
known as vacuoles.
Mechanisms
Assembly of a protein coat drives vesicle formation and
selection of cargo molecules.
Vesicle coat
The vesicle coat serves to sculpt the curvature of a donor
membrane, and to select specific proteins as cargo. It selects
cargo proteins by binding to sorting signals . In this way the
vesicle coat clusters selected membrane cargo proteins into nascent
vesicle buds.
Organelle
An organelle is one of several structures with specialized
functions, suspended in the cytoplasm of a eukaryotic cell.
Organelles were historically identified through the use of some
form of microscopy and were also identified through the use of cell
fractionation.
Organelles include:
mitochondrion
endoplasmic reticulum
golgi apparatus
lysosome
myofibril
centriole nucleus peroxisome ribosome vacuole vesicle
MitochondriaA mitochondrion (from Greek mitos thread + khondrion
granule) is an organelle found in most eukaryotic cells, including
those of plants, animals, fungi. Usually a cell has hundreds or
thousands of mitochondria. The exact number of mitochondria depends
on the cell's level of metabolic activity: more activity means more
mitochondria. Mitochondria can occupy up to 25% of the cell's
cytosol. Mitochondria are sometimes described as "cellular power
plants", because their primary function is to convert organic
materials into energy in the form of ATP.
Mitochondrion structure
Cross-section of a mitochondrion, showing: (1) inner membrane,
(2) outer membrane, (3) cristae, (4) matrix
Depending on the cell type, mitochondria can have very different
overall structures. At one end of the spectrum, the mitochondria
can resemble the standard sausage-shaped organelle pictured to the
right, ranging from 1 to 4 m in length. At the other end of the
spectrum, mitochondria can appear as a highly branched,
interconnected tubular network. Observations of fluorescently
labelled mitochondria in living cells have shown them to be dynamic
organelles capable of dramatic changes in shape. Finally,
mitochondria can fuse with one another, or split in two.
The outer boundary of a mitochondrion contains two functionally
distinct membranes: the outer mitochondrial membrane and the inner
mitochondrial membrane. The outer mitochondrial membrane completely
encloses the organelle, serving as its outer boundary. The inner
mitochondrial membrane is thrown into folds, or cristae, that
project inward. The cristae surface houses the machinery needed for
aerobic respiration and ATP formation, and their folded form
increases that capacity by increasing the surface area of the inner
mitochondrial membrane.
The membranes of the mitochondrion divide the organelle into two
distinct compartments: one within the interior of the
mitochondrion, called the matrix, and a second between the inner
and outer membranes, called the intermembrane space.
The mitochondrial membranes
The outer and inner membranes are composed of phospholipid
bilayers studded with proteins, much like a typical cell membrane.
The two membranes, however, have very different properties. The
outer mitochondrial membrane, which encloses the entire organelle,
is composed of about 50% phospholipids by weight and contains a
variety of enzymes involved in such diverse activities such as the
oxidation of epinephrine (adrenaline), the degradation of
tryptophan, and the elongation of fatty acids.
The inner mitochondrial membrane, in contrast, contains more
than 100 different polypeptides, and has a very high protein to
phospholipid ratio (more than 3:1 by weight, which is about 1
protein for 15 phospholipids). Additionally, the inner membrane is
rich in a an unusual phospholipid, cardiolipin , which is usually
characteristic of bacterial plasma membranes.
The outer mitochondrial membrane contains numerous integral
proteins called porins, which contain a relatively large internal
channel (about 2-3 nm) and allow ions and small molecules to move
in and out of the mitochondrion. Large molecules, however, cannot
traverse the outer membrane. The inner membrane does not contain
porins, however, and is highly impermeable; almost all ions and
molecules require special membrane transporters to enter or exit
the matrix.
The mitochondrial matrix
In addition to various enzymes, the mitochondrial matrix also
contains ribosomes and several molecules of DNA. Thus, mitochondria
possess their own genetic material, and the machinery to
manufacture their own RNAs and proteins. (See: protein synthesis).
This nonchromosomal DNA encodes a small number of mitochondrial
peptides (13 in humans) that are integrated into the inner
mitochondrial membrane, along with polypeptides encoded by genes
that reside in the host cell's nucleus.
Mitochondrial functions
Although the primary function of mitochondria is to convert
organic materials into cellular energy in the form of ATP,
mitochondria play an important role in many important metabolic
tasks, such as: Apoptosis
Glutamate-mediated excitotoxic neuronal injury
Cellular proliferation
Regulation of the cellular redox state
Heme synthesis
Steroid synthesis
Heat production (enabling the organism to stay warm)
Some mitochondrial functions are performed only in specific
types of cells. For example, mitochondria in liver cells contain
enzymes that allow them to detoxify ammonia, a waste product of
protein metabolism. A mutation in the genes regulating any of these
functions can result in a variety of mitochondrial diseases.
Energy conversion
As stated above, the primary function of the mitochondria is the
production of ATP. This is done by metabolizing the major products
of glycolysis, pyruvate and NADH (glycolysis is performed outside
the mitochondria, in the host cell's cytosol). This metabolism can
be performed in two very different ways, depending on the type of
cell and the presence or absence of oxygen.
Adenosine triphosphate (ATP) is the nucleotide known in
biochemistry as the "molecular currency" of intracellular energy
transfer; that is, ATP is able to store and transport chemical
energy within cells. ATP also plays an important role in the
synthesis of nucleic acids. ATP molecules are also used to store
the energy plants make in cellular respiration.
Chemical properties Chemically, ATP consists of adenosine and
three phosphate groups. It has the empirical formula C10H16N5O13P3,
and the chemical formula C10H8N4O2NH2(OH)2(PO3H)3H, with a
molecular mass of 507.184 u. The phosphoryl groups starting with
that on AMP are referred to as the alpha, beta, and gamma
phosphates. The biochemical name for ATP is
9--D-ribofuranosyladenine-5'-triphosphate.
Synthesis ATP can be produced by various cellular processes,
most typically in mitochondria by oxidative phosphorylation under
the catalytic influence of ATP synthase. The main fuels for ATP
synthesis are glucose and fatty acids. Initially glucose is broken
down into pyruvate in the cytosol. Two molecules of ATP are
generated for each molecule of glucose. The terminal stages of ATP
synthesis are carried out in the mitochondrion and can generate up
to 36 ATP.
ATP in the human body The total quantity of ATP in the human
body is about 0.1 mole. The energy used by human cells requires the
hydrolysis of 200 to 300 moles of ATP daily. This means that each
ATP molecule is recycled 2000 to 3000 times during a single day.
ATP cannot be stored, hence its synthesis must closely follow its
consumption.
Other triphosphates Living cells also have other "high-energy"
nucleoside triphosphates, such as guanosine triphosphate. Between
them and ATP, energy can be easily transferred with reactions such
as those catalyzed by nucleoside diphosphokinase : Energy is
released when hydrolysis of the phosphate-phosphate bonds is
carried out. This energy can be used by a variety of enzymes, motor
proteins , and transport proteins to carry out the work of the
cell. Also, the hydrolysis yields free inorganic phosphate and
adenosine diphosphate, which can be broken down further to another
phosphate ion and adenosine monophosphate. ATP can also be broken
down to adenosine monophosphate directly, with the formation of
pyrophosphate. This last reaction has the advantage of being an
effectively irreversible process in aqueous solution.
Reaction of ADP with GTP
ADP + GTP ATP + GDP
There is talk of using ATP as a power source for nanotechnology
and implants. Artificial pacemakers could become independent of
batteries.
Pyruvate: the Krebs cycle
Each pyruvate molecule produced by glycolysis is actively
transported across the inner mitochondrial membrane, and into the
matrix where it is combined coenzyme A to form acetyl CoA. Once
formed, acetyl CoA is fed into the Krebs cycle, also known as the
tricarboxylic acid (TCA) cycle or citric acid cycle. This process
creates 3 molecules of NADH and 1 molecule of FADH2, which go on to
participate in the electron transport chain. With the exception of
succinate dehydrogenase, which is bound to the inner mitochondrial
membrane, all of the enzymes of the Krebs cycle are dissolved in
the mitochondrial matrix.
NADH and FADH2: the electron transport chain
This energy from NADH and FADH2 is transferred to oxygen (O2) in
several steps involving the electron transfer chain. The protein
complexes in the inner membrane (NADH dehydrogenase, cytochrome c
reductase, cytochrome c oxidase) that perform the transfer use the
released energy to pump protons (H+) against a gradient (the
concentration of protons in the intermembrane space is higher than
that in the matrix). An active transport system (energy requiring)
pumps the protons against their physical tendency (in the "wrong"
direction) from the matrix into the intermembrane space.
As the proton concentration increases in the intermembrane
space, a strong diffusion gradient is built up. The only exit for
these protons is through the ATP synthase complex. By transporting
protons from the intermembrane space back into the matrix, the ATP
synthase complex can make ATP from ADP and inorganic phosphate
(Pi). This process is called chemiosmosis and is an example of
facilitated diffusion. Peter Mitchell was awarded the 1978 Nobel
Prize in Chemistry for his work on chemiosmosis. Later, part of the
1997 Nobel Prize in Chemistry was awarded to Paul D. Boyer and John
E. Walker for their clarification of the working mechanism of ATP
synthase.
Use in population genetic studies
Because eggs (ovum) destroy the mitochondria of the sperm that
fertilize them, the mitochondrial DNA of an individual derives
exclusively from the mother. Individuals inherit the other kinds of
genes and DNA from both parents jointly. Because of the unique
matrilineal transmission of mitochondrial DNA, scientists in
population genetics and evolutionary biology often use data from
mitochondrial DNA sequences to draw conclusions about genealogy and
evolution.
The endosymbiotic theory
Mitochondria are unusual among organelles in that they contain
ribosomes and their own genetic material. Mitochondrial DNA is
circular and employs characteristic variants of the standard
eukaryotic genetic code.
These and similar pieces of evidence motivate the endosymbiotic
theory that mitochondria originated as prokaryotic endosymbionts.
Essentially this widely accepted hypothesis postulates that the
ancestors of modern mitochondria were independent bacteria that
colonized the interior of the ancient precursor of all eukaryotic
life.
Ribosome
Figure 1: Ribosome structure indicating small subunit (A) and
large subunit (B). Side and front view. (1) Head. (2) Platform. (3)
Base. (4) Ridge. (5) Central protuberance. (6) Back. (7) Stalk. (8)
Front.
A ribosome is an organelle composed of rRNA (synthesized in the
nucleolus) and ribosomal proteins. It translates mRNA into a
polypeptide chain (e.g., a protein). It can be thought of as a
factory that builds a protein from a set of genetic instructions.
Ribosomes can float freely in the cytoplasm (the internal fluid of
the cell) or bind to another organelle called the endoplasmic
reticulum. Since ribosomes are ribozymes, it is thought that they
might be remnants of the RNA world.
Ribosomes consist of two subunits (Figure 1) that fit together
(Figure 2) and work as one to translate the mRNA into a polypeptide
chain during protein synthesis (Figure 3). Each subunit consists of
one or two very large RNA molecules (known as ribosomal RNA or
rRNA) and multiple smaller protein molecules. Experiments have
shown that the rRNA are the crucial components in protein
synthesis, and that one aspect of the process, peptide transfer,
can occur in the presence of rRNA alone, albeit at a slower rate.
This suggests that the protein components of ribosomes act as a
scaffold that may enhance the ability of rRNA to synthesise
protein.
The structure and function of ribosomes, and their attendant
molecules, known as the translational apparatus, has been of
ongoing research interest since the mid 20th century on through the
early 21st century. A triennial conference is held to discuss the
ribosome. In 1999, the conference was held in Elsinore, Denmark.
The 2002 conference was held in Queenstown, New Zealand [1].
Figure 2: Large (1) and small (2) subunit fit together
Free ribosomes
Free ribosomes occur in all cells, and also in mitochondria and
chloroplasts in eukaryotic cells. Several free ribosomes can
associate on a single mRNA molecule to form a polyribosome or
polysome. Free ribosomes usually produce proteins that are used in
the cytosol or in the organelle they occur in.
Membrane bound ribosomes
When certain proteins are synthesized by a ribosome, it can
become "membrane-bound", associated with the membrane of the
nucleus and the rough endoplasmic reticulum (in eukaryotes only)
for the time of synthesis. They insert the freshly produced
polypeptide chains directly into the ER, from where they are
transported to their destinations. Bound ribosomes usually produce
proteins that are used within the cell membrane or are expelled
from the cell via exocytosis.
The ribosomal subunits of prokaryotes and eukaryotes are quite
similar. However, prokaryotes use 70S ribosomes, each consisting of
a (small) 30S and a (large) 50S subunit, whereas eukaryotes use 80S
ribosomes, each consisting of a (small) 40S and a bound (large) 60S
subunit.[The unit S means Svedberg units, a measure of the rate of
sedimentation of a particle in a centrifuge, where the
sedimentation rate is associated with the size of the particle.
Svedberg units are not additive - two subunits together can have
Svedberg values that do not add up to that of the entire
ribosome.]
Figure 3: Translation (1) of mRNA by a ribosome (2) into a
polypeptide chain (3). The mRNA begins with a start codon (AUG) and
ends with a stop codon (UAG).
In Figure 3, both ribosomal subunits (small and large) assemble
at the start codon (the 5' end of the mRNA). The ribosome uses tRNA
(transfer RNAs which are RNA molecules that carry an amino acid and
present the matching anti-codon, according to the genetic code, to
the ribosome) which matches the current codon (triplet) on the mRNA
to append an amino acid to the polypeptide chain. This is done for
each triplet on the mRNA, while the ribosome moves towards the 3'
end of the mRNA. Usually, several ribosomes are working parallel on
a single mRNA.
Endoplasmic reticulum
The endoplasmic reticulum or ER (endoplasmic means "within the
cytoplasm", reticulum means "little net") modifies proteins, makes
macromolecules, and transfers substances throughout the cell.
Prokaryotic organisms do not have organelles and thus do not have
an ER. ER's base structure and composition is similar to the plasma
membrane, though it is an extension of the nuclear membrane. The ER
is the site of the translation and folding of and transport of
proteins that are to become part of the cell membrane (e.g.,
transmembrane receptors and other integral membrane proteins) as
well as proteins that are to be secreted or "exocytosed" from the
cell (e.g., digestive enzymes).
Structure
Figure 1: Image of nucleus, endoplasmic reticulum and Golgi
apparatus.(1) Nucleus. (2) Nuclear pore. (3) Rough endoplasmic
reticulum (RER). (4) Smooth endoplasmic reticulum (SER). (5)
Ribosome on the rough ER. (6) Proteins that are transported. (7)
Transport vesicle. (8) Golgi apparatus. (9) Cis face of the Golgi
apparatus. (10) Trans face of the Golgi apparatus. (11) Cisternae
of the Golgi apparatus.
The ER consists of an extensive membrane network of tubes and
cisternae (sac-like structures). The membrane encloses a space, the
cisternal space (or internal lumen) from the cytosol. This space is
acting as a gateway. Parts of the ER membrane are continuous with
the outer membrane of the nuclear envelope, and the cisternal space
of the ER is continuous with the space in between the two layers of
the nuclear envelope.
Parts of the ER are covered with ribosomes (which assemble amino
acids into proteins based on instructions from the nucleus). Their
rough appearance under electron microscopy led to their being
called rough ER (RER), other parts are free of ribosomes and are
called smooth ER (SER). The ribosomes on the surface of the rough
ER insert the freshly produced proteins directly into the ER, which
processes them and then passes them on to the Golgi apparatus (Fig.
1). Rough and smooth ER differ not only in appearance, but also in
function.
Rough ERThe coarse ER manufactures and transports proteins
destined for membranes and secretion. It synthesizes membrane,
organellar, and excreted proteins. Minutes after proteins are
synthesized most of them leave to the Golgi apparatus within
vesicles. The rough ER also modifies, folds, and controls the
quality of proteins.
Smooth ERThe smooth ER has functions in several metabolic
processes. It takes part in the synthesis of various lipids (e.g.,
for building membranes such as phospholipids), fatty acids and
steroids (e.g., hormones), and also plays an important role in
carbohydrate metabolism, detoxification of the cell (enzymes in the
smooth ER detoxify chemicals), and calcium storage. It also is a
large transporter of nutrient found in each cell.
FunctionsThe endoplasmic reticulum serves many general
functions, including the facilitation of protein folding, and the
transport of proteins. Correct folding of newly made proteins is
made possible by several ER proteins including: PDI, Hsc70 family ,
calnexin , calreticulin, and the peptidylpropyl isomerase family .
Only properly folded proteins are transported from the RER to the
Golgi complex.
Transport of proteinsSecretory proteins are moved across the ER
membrane. Proteins that are transported by the ER and from there
throughout the cell are marked with an address tag that are called
a signal sequence. Gnter Blobel was awarded the 1999 Nobel Prize in
Physiology or Medicine for his discovery of these signal sequences
in 1975. The N-terminus (one end) of a polypeptide chain (e.g., a
protein) contains a few amino acids that work as an address tag,
which are removed when the polypeptide reaches its destination.
Proteins that are destined for places outside the ER are packed
into transport vesicles and moved along the cytoskeleton towards
their destination. The ER is also part of a protein sorting
pathway.
Other functions Insertion of proteins into the ER membrane.
Integral proteins need to be inserted into the ER membrane after
they are synthesized. Insertion into the ER membrane requires the
correct topogenic sequences.
Glycosylation. Glycosylation involves the attachment of
oligosaccharides.
Disulfide bond formation and rearrangement. Disulfide bonds
stabilize the tertiary and quaternary structure of many
proteins.
Sarcoplasmic reticulum. The endoplasmic reticulum found in
muscle fibers is called sarcoplasmic reticulum.
Categories: OrganellesGolgi apparatus
The Golgi apparatus (Golgi body, Golgi complex, or dictyosome)
is an organelle found in most eukaryotic cells, including those of
plants and animals (but not most fungi). The name comes from
Italian anatomist Camillo Golgi, who identified it in 1898. Its
primary function is to process proteins targeted to the plasma
membrane, lysosomes or endosomes and those that will be secreted
from the cell, and sort them within vesicles. Thus, it functions as
a central delivery system for the cell.
Most of the transport vesicles that leave the endoplasmic
reticulum (ER), specifically rough ER, are transported to the Golgi
apparatus, where they are modified, sorted and shipped towards
their final destination. The Golgi apparatus is present in most
eukaryotic cells, but tends to be more prominent where there are a
lot of substances, such as enzymes, being secreted.
Structure
Figure 1: Image of nucleus, endoplasmic reticulum and Golgi
apparatus: (1) Nucleus, (2) Nuclear pore, (3) Rough endoplasmic
reticulum (RER), (4) Smooth endoplasmic reticulum (SER), (5)
Ribosome on the rough ER, (6) Proteins that are transported, (7)
Transport vesicle, (8) Golgi apparatus, (9) Cis face of the Golgi
apparatus, (10) Trans face of the Golgi apparatus, (11) Cisternae
of the Golgi apparatus, (12) Secretory vesicle, (13) Plasma
membrane, (14) Exocytosis, (15) Cytoplasm, (16) Extracellular
space.
The structure and internal function of the Golgi apparatus is
quite complex and is the subject of scientific dispute. The Golgi
apparatus consists, like the ER, of membranous structures. It is
made up of a stack of flattened cisternae and similar vesicles. The
cis face is the side facing the ER, the medial region is in the
middle while the trans face is directed towards the plasma membrane
(Fig. 1). The cis and trans faces have different membranous
compositions.
FunctionThe transport vesicles from the ER fuse with the cis
face of the Golgi apparatus (to the cisternae) and empty their
protein content into the Golgi lumen. The proteins are then
transported through the medial region towards the trans face and
are modified on their way.
The transport mechanism itself is not yet clear; it could happen
by cisternae progression (the movement of the apparatus itself,
building new cisternae at the cis face and destroying them at the
trans face) or by vesicular transport (small vesicles transport the
proteins from one cisterna to the next, while the cisternae remain
unchanged). Lately, it is also proposed that the cisternae are
interconnected and the transport of cargo molecules within the
Golgi is due to diffusion, while the localisation of Golgi resident
proteins is achieved by an unknown mechansim.
Once the proteins reach the trans face, they are embedded into
coated transport vesicles and brought to their final destinations.
An example is the modification of glycoproteins (used in cell
membranes). Vesicles from the ER contain simplified glycosylated
proteins. In the Golgi Apparatus, carbohydrates are attached and
removed from these glycoproteins, creating a diversity of
carbohydrate structures on the proteins. After they have been
secreted in to the cell the vesicles fuse to the cell membrane and
release their contents.
As well as protein modification, Golgi apparatus is involved in
the transport of lipids around the cell as well creating lysosomes
-- organelles involved in digestion.
Categories: Organelles | Eponymous anatomical
structuresLysosome
Lysosomes are organelles that contain digestive enzymes to
digest macromolecules. They are built in the Golgi apparatus. At pH
4.8, the interior of the lysosomes is more acidic than the cytosol
(pH 7). The lysosome single membrane stabilizes the low pH by
pumping in protons (H+) from the cytosol, and also protects the
cytosol, and therefore the rest of the cell, from the degradative
enzymes within the lysosome. The digestive enzymes need the acidic
environment of the lysosome to function correctly. All these
enzymes are produced in the endoplasmic reticulum, and transported
and processed through the Golgi apparatus. The Golgi apparatus
produces lysosomes by budding.
The most important enzymes in lysosomes are:
Lipase, which digests lipids,
Carbohydrases , which digest carbohydrates (e.g., sugars),
Proteases, which digest proteins,
Nucleases, which digest nucleic acids.
The lysosomes are used for the digestion of macromolecules from
phagocytosis (ingestion of cells), from the cell's own recycling
process (where old components such as worn out mitochondria are
continuously destroyed and replaced by new ones, and receptor
proteins are recycled), and for autophagic cell death, a form of
programmed self-destruction of the cell, which means that the cell
is digesting itself. Other functions include digesting foreign
bacteria that invade a cell and helping repair damage to the plasma
membrane by serving as a membrane patch, sealing the wound.
There are a number of illnesses that are caused by the
malfunction of the lysosomes or one of their digestive proteins,
e.g., Tay-Sachs disease, or Pompe's disease. These are caused by a
defective or missing digestive protein, which leads to the
accumulation of substrates within the cell, resulting in impaired
cell metabolism. Broadly, these can be classified as
mucopolysaccharidoses, GM2 gangliosid