Cell Biology (Bio 108) - The Chemistry of the Cell

The Chemistry of the CellCan be structured around 5 principles:

1. The importance of carbon2. The importance of water3. The importance of selectively permeable membranes4. The importance of synthesis by polymerization of small

molecules5. The importance of self-assembly

Chemistry of CellsCells – composed of water, inorganic ions

and carbon-containing (organic) molecules

Review:Atoms- smallest unit of the chemical elements

Ionic bonds –there is transfer of e¯s from one atom to a second atom

Na + Cl → Na+ + Cl− → NaCl

Symbol Atomic # Atomic mass # of Chemical Bonds

Hydrogen H 1 1 1Carbon C 6 12 4

Nitrogen N 7 14 3Oxygen O 8 16 2Sulfur S 16 32 2

Covalent Bonds- formed when atoms share their valence e¯ s

a. Nonpolar - eg. O2; H2

b. Polar - eg. H2O

Nonpolar CB> Polar CB> Ionic Bond>WanderWaals

c. Organic molecules – 80-90% of the dry weight of most cells - carbohydrates, lipids, proteins, and nucleic acids

Biomolecules Simple forms

Carbohydrates monosaccharidesProteins amino acidsNucleic acids nucleotidesLipid fatty acid and glycerol

Molecular Composition of Cells:a. Water –abundant molecule (≥ 70% of total cell mass)

- it is polar and it can form H-bonds with each other or with polar molecules

b. Inorganic ions – Na , K , Mg⁺ ⁺ 2 , Ca⁺ 2⁺ , phosphate (HPO42¯ , Cl¯ and bicarbonate (HCO3¯)

- 1% or less of the cell mass - these ions are involved in number of aspects of cell metabolism

Water Molecules are Polar

-This accounts for its• cohesiveness,• temperature-stabilizing capacity and• solvent properties of water.

The Importance of Synthesis by PolymerizationMacromolecules Are Responsible for Most of the Form and Function in Living Systems

-Cells contain Three different Kinds of Macromolecules• informational • storage and • structural

Biological Polymer

Proteins Nucleic Acids Polysaccharides

Kind of macromolecule

Informational Informational Storage Structural

Examples Enzymes, DNA, RNA Starch, Glycogen

Cellulose

Hormones,

Antibodies

Repeating monomers

Amino Acids Nucleotides Monosaccharides Monosaccharides

Number of kinds of repeating units

20 4 in DNA;4 in RNA

One or a few One or a few

Carbohydrates

-the most abundant class of organic compounds found in living organisms.- include simple sugars and polysaccharides

-They fill numerous roles in living things, such as the storage and transport of energy (eg: starch, glycogen) and structural components (eg: cellulose in plants and chitin).

General Formula: (CH2O)nSugars: 3 C= trioses 6 C= hexoses 4 C= tetroses 7 C= heptoses 5 C= pentoses

Aldoses and Ketoses

OROR

D-glucose an aldose an aldohexose

D-fructose a ketose a ketohexose

Fig. 2-4: Stereoisomers (chirality): Mirror images – depends on an asymmetric atom.

Number ofCarbons Category Name Examples

4 Tetrose Erythrose, Threose

5 PentoseArabinose, Ribose, Ribulose, Xylose, Xylulose, Lyxose

6 Hexose

Allose, Altrose, Fructose, Galactose, Glucose, Gulose, Idose, Mannose, Sorbose, Talose, Tagatose

7 Heptose Sedoheptulose

Monosaccharide classifications based on the number of carbons

D-Erythrose D-Threose

Tetroses Pentoses

D-Ribose D-Arabinose D-Xylose D-Lyxose

The ring form of ribose is a component of ribonucleic acid (RNA).   Deoxyribose, which is missing an oxygen at position 2, is a component of deoxyribonucleic acid (DNA). In nucleic acids, the hydroxyl group attached to carbon number 1 is replaced with nucleotide bases.

Ribose Deoxyribose

Hexoses

Hexoses, such as the ones illustrated here, have the molecular formula C6H12O6.

German chemist Emil Fischer (1852-1919) Identified the stereoisomers for these aldohexoses in 1894. He received the 1902 Nobel Prize for chemistry for his work.

D-Glucose D-Mannose D-Galactose

Glucose is by far the most common carbohydrate and classified as a monosaccharide, an aldose, a hexose, and is a reducing sugar. It is also known as dextrose .

-also called blood sugar as it circulates in the blood at a concentration of 65-110 mg/mL of blood.

Fructose is more commonly found together with glucose and sucrose in honey and fruit juices. Fructose, along with glucose are the monosaccharides found in disaccharide, sucrose.

-the most important ketose sugar- common name for fructose is levulose

Disaccharide Description Component monosaccharides

sucrose common table sugar

glucose 1α→2 fructose

maltose product of starch hydrolysis

glucose 1α→4 glucose

lactose main sugar in milk galactose 1β→4 glucose

Disaccharide descriptions and components

Disaccharides consist of two simple sugars

Sucrose Lactose Maltose

Oligosaccharide

- a saccharide polymer containing a small number (typically three to ten) simple sugars- commonly found on the plasma membrane of animal cells where they can play a role in cell-cell recognition.

Polysaccharides are polymers of simple sugarsMany polysaccharides, unlike sugars, are insoluble in water.Dietary fiber includes polysaccharides and oligosaccharides that are resistant to digestion and absorption in the human small intestine but which are completely or partially fermented by microorganisms in the large intestine.

StarchStarch is the major form of stored carbohydrate in plants. Starch is composed of a mixture of two substances:

amylose, an essentially linear polysaccharide, and amylopectin, a highly branched polysaccharide.

Both forms of starch are polymers of α-D-Glucose.

Natural starches contain 10-20% amylose and 80-90% amylopectin. Amylose forms a colloidal dispersion in hot water (which helps to thicken gravies) whereas amylopectin is completely insoluble.

•Amylose molecules consist typically of 200 to 20,000 glucose units which form a helix as a result of the bond angles between the glucose units.

Amylose

Amylopectin differs from amylose in being highly branched. Short side chains of about 30 glucose units are attached with 1α→6 linkages approximately every twenty to thirty glucose units along the chain. Amylopectin molecules may contain up to two million glucose units.

Amylopectin The side branching chains are clustered together within the amylopectin molecule

GlycogenGlucose is stored as glycogen in animal tissues by the

process of glycogenesis. When glucose cannot be stored as glycogen or used immediately for energy, it is converted to fat. Glycogen is a polymer of α-D-Glucose identical to amylopectin, but the branches in glycogen tend to be shorter (about 13 glucose units) and more frequent. The glucose chains are organized globularly like branches of a tree originating from a pair of molecules of glycogenin, a protein with a molecular weight of 38,000 that acts as a primer at the core of the structure. Glycogen is easily converted back to glucose to provide energy.

Glycogen

CelluloseCellulose is a polymer of β-D-Glucose, which in contrast to starch, is oriented with -CH2OH groups alternating above and below the plane of the cellulose molecule thus producing long, unbranched chains. The absence of side chains allows cellulose molecules to lie close together and form rigid structures. Cellulose is the major structural material of plants. Wood is largely cellulose, and cotton is almost pure cellulose. Cellulose can be hydrolyzed to its constituent glucose units by microorganisms that inhabit the digestive tract of termites and ruminants.

Cellulose

ChitinChitin is an unbranched polymer of N-Acetyl-D-glucosamine. It is found in fungi and is the principal component of arthropod and lower animal exoskeletons, e.g., insect, crab, and shrimp shells. It may be regarded as a derivative of cellulose, in which the hydroxyl groups of the second carbon of each glucose unit have been replaced with acetamido (-NH(C=O)CH3) groups.

Chitin

GlycosaminoglycansGlycosaminoglycans are found in the lubricating fluid of the joints and as components of cartilage, synovial fluid, vitreous humor, bone,and heart valves. - are long unbranched polysaccharides containing repeating

disaccharide units that contain either of two amino sugar compounds -- N- acetylgalactosamine or N-acetylglucosamine, and a uronic acid such as glucuronate (glucose where carbon six forms a carboxyl group).

- are negatively charged, highly viscous molecules sometimes called mucopolysaccharides.

- The physiologically most important glycosaminoglycans are hyaluronic acid, dermatan sulfate, chondroitin sulfate, heparin, heparan sulfate, and keratan sulfate. Chondroitin sulfate is composed of β-D-glucuronate linked to the third carbon of N- acetylgalactosamine-4-sulfate as illustrated here. Heparin is a complex mixture of linear polysaccharides that have anticoagulant properties.

Heparin

Chondroitin Sulfate

II. Lipids- diverse group of non-polar biomolecules- have the ability to dissolve in organic solvents (chloroform

or benzene but not in water.

Three Major Roles in Cells1. provide an important form of energy storage2. as major component of cell membrane (great

importance in cell biol3. play important role in cell signaling as

a. steroid hormones (eg. Estrogen and testosterone)b. messenger molecules – convey signals from cell

surface receptors to targets within the cell.

TRIGLYCERIDES/FATS

-consist of three fatty acids linked to a glycerol molecule

- insoluble in water and therefore accumulate as fat droplets in the cytoplasm.

- can be broken down for use in energy-yielding reactions( more efficient form

of energy storage than carbohydrates, yielding more than twice as much

energy per weight of material broken down.

Fatty acids- consist of long hydrocarbon chains, most frequently containing 16 or 18 carbon atoms, with a carboxyl group (COO-) at one end

-maybe saturated or unsaturated fatty acids

Saturated fatty Acids - lack double bonds (eg. Stearic

acid) - common component of animal

fats (solid at room T)Unsaturated fatty acids

- possesing double bonds - double bonds create kinks in the

molecules - found in vegetable fats(liquid at

room T)

Phospholipids- principal components of cell membrane - are amphipathic molecules (part water-

soluble and part water-insoluble )

Figure 2.7. Structure of phospholipids Glycerol phospholipids contain two fatty acids joined to glycerol. The fatty acids may be different from each other and are designated R1 and R2. The third carbon of glycerol is joined to a phosphate group (forming phosphatidic acid), which in turn is frequently joined to another small polar molecule (forming phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine, or phosphatidylinositol). In sphingomyelin, two hydrocarbon chains are bound to a polar head group formed from serine instead of glycerol.

Figure 2.9. Cholesterol and steroid hormones Cholesterol, an important component of cell membranes, is an amphipathic molecule because of its polar hydroxyl group. Cholesterol is also a precursor to the steroid hormones, such as testosterone and estradiol (a form of estrogen). The hydrogen atoms bonded to the ring carbons are not shown in this figure.

Nucleic AcidsDNA and RNA- the principal informational

molecules of the cell

DNA - Deoxyribonucleic acid (has a unique role as the genetic material)

- a double-stranded molecule consisting of two polynucleotide chains running in opposite directions

- contains two purines (adenine and guanine) and two pyrimidines (cytosine and thymine).

- 2′-deoxyribose sugar

RNA- Ribonucleic acid - single-stranded - Adenine, guanine, and cytosine are also

present in RNA, but RNA contains uracil in place of thymine

- ribose sugar - different types of RNA participate in a number of cellular activities

a. Messenger RNA (mRNA) -carries information from DNA to the ribosomes, where it serves as a template for protein synthesis

b. Ribosomal RNA(rRNA) involves in protein synthesis

c. Transfer RNA(tRNA)

*polymerization of nucleotides to form nucleic acids involves the formation of phosphodiester bonds between the 5′ phosphate of one nucleotide and the 3′ hydroxyl of another

oligonucleotide - a short polymer of only a few nucleotides

the large polynucleotides that make up cellular RNA and DNA may contain thousands or millions of nucleotides, respectively.

Polynucleotides are always synthesized in the 5′ to 3′ direction, with a free nucleotide being added to the 3′ OH group of a growing chain.

Figure 2.10. Components of nucleic acids Nucleic acids contain purine and pyrimidine bases linked to phosphorylated sugars. A nucleic acid base linked to a sugar alone is a nucleoside. Nucleotides additionally contain one or more phosphate groups.

Figure 2.12. Complementary pairing between nucleic acid bases

Figure 2.11. Polymerization of nucleotides A phosphodiester bond is formed between the 3 hydroxyl group of one nucleotide and ′the 5 phosphate group of another. A ′polynucleotide chain has a sense of direction, one end terminating in a 5 ′phosphate group (the 5 end) and the other ′in a 3 hydroxyl group (the 3 end).′ ′

Proteins-primary responsibility is to execute the tasks directed by that information in nucleic acids-the most diverse of all macromolecules (each cell contains several thousand different proteins, which perform a wide variety of functions)

1. serving as structural components of cells and tissues2. acting in the transport and storage of small molecules

(e.g., the transport of oxygen by hemoglobin3. transmitting information between cells (e.g., protein

hormones)4. and providing a defense against infection (e.g., antibodies)

-the most fundamental property of proteins is their ability to act as enzymes-direct virtually all activities of the cell.-polymers of 20 different amino acids

Figure 2.13. Structure of amino acids Each amino acid consists of a central carbon atom (the α carbon) bonded to a hydrogen atom, a carboxyl group, an amino group, and a specific side chain (designated R). At physiological pH, both the carboxyl and amino groups are ionized, as shown.

Figure 2.14. The amino acids The three-letter and one-letter abbreviations for each amino acid are indicated. The amino acids are grouped into four categories according to the properties of their side chains: nonpolar, polar, basic, and acidic.

Figure 2.15. Formation of a peptide bond The carboxyl group of one amino acid is linked to the amino group of a second.

Protein structure 1. primary structure 2. secondary structure 3. tertiary structure 4. quaternary structure

Primary Structure -the sequence of amino acids in its polypeptide chain

Figure 2.16. Amino acid sequence of insulin

Secondary structure- the regular arrangement of amino acids within localized regions of the polypeptide.

Figure 2.19. Secondary structure of proteins

Tertiary structure-the folding of the polypeptide chain as a result of interactions between the side chains of amino acids that lie in different regions of the primary sequence

Figure 2.20. Tertiary structure of ribonuclease

Quaternary structure- consists of the interactions between different polypeptide chains in proteins composed of more than one polypeptide.

Figure 2.21. Quaternary structure of hemoglobin

Bioenergetics, Enzymes and Metabolism

Bioenergetics: The Flow of Energy in the

Cell-the study of the various types of energy trans-formations that occur in living organisms

-the prodn of energy, its storage and its use are central to the economy of the cell

- the capacity to do work (the capacity to change or move something).

-cell require energy to do all their work, including the synthesis of sugars from CO2 and H2O in photosynthesis, the contraction of muscles and the replication of DNA

POTENTIAL ENERGY- several forms of PE are biologically significant

1. stored in the bonds connecting atoms in molecules

2. concentration gradient 3. electric potential (the energy of charge

separation)

Energy

Cells Need Energy to Cause Six Different Kinds of Biological Work

1. Synthetic Work -changes in chemical bonds (formationand generation of new molecules)e.g. process of photosynthesis

2. Mechanical Work- physical change in the position or orientation of a cell or some part of ite.g. Contraction of weightlifter’s muscleor movement of cell thru its flagella

3. Concentration Work - movement of molecules across amembrane against a concentrationgradiente.g. Na+-K+ pumps across plasma membrane

4. Electrical Work - movement of ions across a membraneagainst an electrochemical gradiente.g. Membrane potential of mitochondrion(generated by active proton transport)

5. Heat - an increase in temperature that is useful to warm blooded animalse.g. Use to maintain body T near 37oC wheremetabolism is most efficient by warm-bloodedanimals

6. Bioluminescence – production of lighte.g. Seen during courtship of fireflies, in dino-flagellates, luminous toadstools, deep-sea fish

Most organisms obtain energy either from sunlight or from organic food molecules:

a. Phototrophs – “light-feeders” (plants, algae, cyanobacteria and photosynthesizing bacteria).

b. Chemotrophs- “chemical-feeders” (all animals,fungi,

protists and most bacteria)Energy flows through the biosphere continuously

System-By convention, the restricted portion of the universe

under consideration e.g. Reaction/process occurring in a beaker of

chemicals or in a cell Surroundings - referred to all the rest of the universe

2 types of System:1. Open System - can exchange energy with its

surroundings - can use incoming energy to increase

its orderliness thus decreasing its entropy.2. Closed System – can not exchange energy w/ its

surroundings - tends toward equilibrium and

increases its entropy

*All living organisms are open systems, exchanging energy freely with their surroundings.

-the study of the changes in energy that accompany events in the universe.

1st Law of thermodynamics(Law of conservation of Energy)

- E is neither created nor destroyed but can be converted from one form to another

energy stored = energy in – energy out or

∆E = Eproducts - Ereactants (chemical reactions)

In the case of biological rxns and processes, we are more interested in the change in enthalpy or heat constant (H)

Thermodynamics

∆H = ∆E + ∆(PV) = ∆E

∆H = Hproducts - Hreactants

*if the heat content of the products is less than that of the reactants, ∆H will be negative and the rxn is said to beExothermic•If the heat content of the products is greater than that of reactants, ∆H will be positive and the rxn is endothermic

-energy can be expressed in the same units of measurement such as cal or kilocalorie

2nd Law of thermodynamics- the universe and its parts (including living

systems) become increasingly disorganized (Entropy)

Energy transformations thus increased the amount of entropy of a system.

*only E that is in an organized state-called free energy-can be used to do work

Free energy or G- a measure of the potential energy of a system which is a function of the enthalpy (H) and entropy (S)

Enthalpy(H)Heat-in a chemical rxn, the E of the reactants or products is equal to their total bond energies (heat released or absorbed during a chemical reaction)

Entropy(S)- a measure of the degree of disorder or randomness in a system; the higher the entropy, the greater the disorder resulting frm a rxn

-thus determines its chemical equilibrium and predicts in which direction the reaction will proceed under any given set of conditions

*many biological rxns (such as synthesis of macromolecules) are thermodynamically unfavorable under cellular conditions (ΔG>0or-)(for the reaction to proceed an additional source of energy is required)

A B ΔG=+10kcal/mol

How?: by coupling the conversion of A to B with an energetically favorable

reactionC D ΔG= -20kcal/mol

THUS: A + C B + D ΔG= -10kcal/mol

* Enzymes are responsible for carrying out such coupled reactions in a coordinated manner

*the cell uses this basic mechanism to drive many energetically unfavorable reactions that must take place in biological system

At constant T & P, it is possible to predict the direction of a chemical rxn by using G.

G =H-TS where T= °K

-the change in Free Energy(ΔG) determines the direction of a chemical reaction

Free Energy change, ΔG = G products – G reactants if ΔG(-) for a chemical reaction, forward rxn occurs

if ΔG(+) reverse reaction occursif ΔG = 0, both forward and reverse rxns occur at equal

rates; the rxn is at equilibrium

A B

Standard Free-Energy Change (ΔG °) ΔG° = -RTln K where K= [B]/[A]

Endergonic Reactions– chemical reactions that require input of E.eg. CO2 + H2O CH2O + O2

Exergonic Reactions-rxns that convert molecules with more free energy to molecules with less- and, therefore, that release energy as they proceed.eg. C6H12 O6 + O2 CO2 + H2O

Equilibrium vs Steady State MetabolismAt equilibrium: 1. reaction has stopped (no net reaction are possible)

2. no energy can be released 3. no work can be done and order of living state can

notbe maintained

*The continual flow of oxygen and other materials into and out of cells allows cellular metabolism to exist in a Steady state. ( thus life is possible because living cells maintain this state).

Coupled Reactions: ATP

-Energy –liberating reactions are thus coupled to energy-requiring reactions.

-Adenosine 5’-triphosphate (ATP) plays a central role in this process

• by acting as a store of free energy within the cell

Figure 2-24. In adenosine triphosphate (ATP), two high-energy phosphoanhydride bonds (red) link the three phosphate groups.

-The bonds between the phosphates in ATP (HIGH- ENERGY BONDS)-large amount of free energy is released when hydrolyzed within

the cell (≈ΔG approx = 12kcal/mol)from ATP to ADP and Pi

-energy released from the breakdown of ATP is used to power the energy-requiring processes in cells.-known as the universal energy carrier, ATP serves to more

efficiently couple the E released by the breakdown of food molecules to theE required by the diverse endergonic processes in the cell.

Figure 2-25. The ATP cycle. ATP is formed from ADP and Pi by photosynthesis in plants and by the metabolism of energy-rich compounds in most cells. The hydrolysis of ATP to ADP and Pi is linked to many key cellular functions; the free energy released by the breaking of the phosphoanhydride bond is trapped as usable energy.

Coupled Reactions: Oxidation-Reduction-involve the transfer of hydrogen atoms - a molecule is said to be oxidized when it loses electrons and it is said to be reduced when it gains electrons- a reducing agent is thus an electron donor; an oxidizing agent is an electron acceptor-although oxygen is the final electron acceptor in the cell, other molecules can act as oxidizing agents-a single molecule can be an electron acceptor in one reaction and an electron donor in another.

1. NAD and FAD can become reduced by accepting electrons from hydrogen atoms removed from other molecules

2. NADH + H+ and FADH2 in turn, donate these electronsto other molecules in other locations within the cells

3. Oxygen is the final electron acceptor (oxidizing agent)in a chain of oxidation-reduction reactions that provide energy for ATP production.

Nicotinamide adenine dinucleotide

Rxn site

+ 2H

N

H

+H

H

NAD+

(Oxidized state)NADH

(Reduced state)

Flavin Adenine Dinucleotide (FAD)(Oxidized Form)

+ 2H

H3C

H3C

N

N

N

NH

O

H

H

O

FADH2 (Reduced form)

The Central Role of Enzymes as Biological Catalysts

Enzymes—catalysts that increase the rate of virtually all the chemical reactions within cells.

2 Fundamental Properties:1. they increase the rate of chemical

reactions without themselves being consumed or permanently altered by the reaction.

2. they increase reaction rates without altering the chemical equilibrium between reactants and products.

Active site -a specific region of the enzyme where the substrate binds

Figure 2.23. Enzymatic catalysis of a reaction between two substrates The enzyme provides a template upon which the two substrates are brought together in the proper position and orientation to react with each other.

Figure 2.22. Energy diagrams for catalyzed and uncatalyzed reactions

Figure 2.24. Models of enzyme-substrate interaction (A) In the lock-and-key model, the substrate fits precisely into the active site of the enzyme. (B) In the induced-fit model, substrate binding distorts the conformations of both substrate and enzyme. This distortion brings the substrate closer to the conformation of the transition state, thereby accelerating the reaction.

Coenzymes -molecules that work together with enzymes to enhance

reaction rates.-are not irreversibly altered by the reactions in which they are involved but are recycled and can participate in multiple enzymatic reactions.

Prosthetic groups are small molecules bound to proteins in which they play critical functional roles

-either small organic molecules (coenzymes) or inorganic like metal ions (cofactors)

Coenzyme Related vitamin Chemical reaction

NAD+, NADP+ Niacin Oxidation-reductionFAD Riboflavin (B2) Oxidation-reduction

Thiamine pyrophosphate Thiamine (B1) Aldehyde group transfer

Coenzyme A Pantothenate Acyl group transferTetrahydrofolate Folate Transfer of one-carbon

groupsBiotin Biotin CarboxylationPyridoxal phosphate Pyridoxal (B6) Transamination

Table 2.1. Examples of Coenzymes and Vitamins

Figure 2.29. Allosteric regulation In this example, enzyme activity is inhibited by the binding of a regulatory molecule to an allosteric site. In the absence of inhibitor, the substrate binds to the active site of the enzyme and the reaction proceeds. The binding of inhibitor to the allosteric site induces a conformational change in the enzyme and prevents substrate binding. Most allosteric enzymes consist of multiple subunits

Metabolism

Metabolism-all of the reactions in the body that involve

energy transformation

2 Categories:1. Anabolism – reactions require the input of energy and

include the synthesis of large energy-storage molecules, including glycogen, fat and protein.

2. Catabolism – reactions release energy, usually by the breakdown of larger organic molecules into smaller molecules.

*The catabolic reactions that break down glucose, fatty acid, and amino acids serve as the primary source s of energy for the synthesis of ATP.

*Some of the chemical-bond energy in glucose is transferred to the chemical-bond energy in ATP.

Fig.3 Three Stages of Metabolism

The Generation of ATP from Glucose-breakdown of glucose (major source of cellular energy)

2 Stages:1. Glycolysis2. Tricarboxylic acid (TCA) cycle

Glycolysis- initial stage in the breakdown of glucose (aerobic cells)- common to all cells (occurs in the cytosol)-occurs in the absence of O2 (can provide all the metabolic energy of anaerobic organisms)- conversion of glucose to pyruvate with the net gain of 2 molecules of ATP

Glu + 2ADP + 2Pi + 2NAD+ 2 Pyruvate + 2ATP + 2NADH + 2H+ +2H2O

Enzymes: (important regulatory points of glycolytic pathway)1. Hexokinase2. phosphofructokinase- key control element which is inhibited

by increased levels of ATP

Figure 2.32. Reactions of glycolysis Glucose is broken down to pyruvate, with the net formation of two molecules each of ATP and NADH. Under anaerobic conditions, the NADH is reoxidized by the conversion of pyruvate to ethanol or lactate. Under aerobic conditions, pyruvate is further metabolized by the citric acid cycle. Note that a single molecule of glucose yields two molecules each (shadow boxes) of the energy-producing three-carbon derivatives.

Glycogenesis – the formation of glycogen from glucose (see fig. – enzyme=glycogen synthase)

Glycogenolysis- the conversion of glycogen to glucose -6-P

(enzyme= glycogen phosphorylase)

Gluconeogenesis- the conversion of noncarbohydrate molecules (not just lactic acid but also

amino acids and glycerol) through pyruvic acid to glucoseCori Cycle

- gluconeogenesis in the liver allows depleted skeletal muscle glycogen to be restored w/in 48 hrs.- it is a two-way traffic between skeletal muscles and the liver

In the liver are enzymes: glu-6-phosphatase & lactic dehydrogenase

Glycogen

Glu-6-phosphate

Pyruvic acid

Lactic acid

Glycogen

Glu-6-phosphate

Pyruvic acid

Lactic acid

The Cori Cycle

Skeletal Muscles Liver

Exercise1

Rest9

GlucoseBlood

Blood

2

3

4

5

8

7

6

TCA or Krebs cycle- occurs in the mitochondria (matrix)- leads to the final oxidation of the carbon atom s to carbon dioxide

Figure 2.33. Oxidative decarboxylation of pyruvate .Pyruvate is converted to CO2 and acetyl CoA, and one molecule of NADH is produced in the process. Coenzyme A (CoA-SH) is a general carrier of activated acyl groups in a variety of reactions.

Figure 2.34. The citric acid cycle A two-carbon acetyl group is transferred from acetyl CoA to oxaloacetate, forming citrate. Two carbons of citrate are then oxidized to CO2 and oxaloacetate is regenerated. Each turn of the cycle yields one molecule of GTP, three of NADH, and one of FADH2.

Electron Transport and Oxidative Phosphorylation

-built into the foldings, cristae of the inner mitochondrial membrane are a series of molecules that serve as electron transport system during aerobic respiration

-the molecules of electron transport system are fixed in position within the inner mitochondrial

membrane in such a way that they can pick up electrons from NADH and FADH2 and transport them in a definite sequence and direction.

-the electron transport chain thus act as an oxidizing agent for NAD and FAD.

Oxidative Phosphorylation- the production of ATP thru the coupling of the electron-transport system with the

phosphorylation of ADP.

Figure 2.35. The electron transport chain Electrons from NADH and FADH2 are transferred to O2 through a series of carriers organized into four protein complexes in the mitochondrial membrane. The free energy derived from electron transport reactions at complexes I, III, and IV is used to drive the synthesis of ATP.

Chemiosmosis in mitochondria

ATP Balance SheetSummary: Theoretical ATP yield =36 to 38 ATP per glucose

Actual ATP yield = 30 to 32 ATP per glucose (allowingfor the costs of transport)

Phases of Respiration

Subsrate-level phosphorylation

Reduced Coenzymes ATP Made byOxidative Phosphorylation*

Glucose to pyruvate (in cytoplasm)

2 ATP (net gain)

2 NADH, but usually goes into mitochondria as 2 FADH2

1.5 ATP per FADH2 X 2 = 3ATP

Pyruvate to acetyl CoA(x2 bec one glu yields 2 pyruvates)

None 1 NADH (X2) = 2NADH 2.5ATP per NADH x 2 = 5ATP

Krebs cycle (x2 bec one glucose yields 2 Krebs cycles)

1 ATP (X2) = 2 ATP

3 NADH (X2) 2.5ATP per NADH x 3 =7.5 ATP X 2 = 15 ATP1.5 ATP per FADH2 X 2 = 3ATP

SUBTOTALS 4 ATP 26 ATPGRAND TOTAL 30 ATP

Table 3. ATP Yield per Glucose in Aerobic Respiration

*Theoretical estimates of ATP production from oxidation phosphorylation are 2 ATP per FADH2 and 3 ATP per NADH. If these numbers are used, a total of 32 ATP will be calculated as arising from oxidative phosphorylation. This is increased to 34 ATP IF the cytoplasmic NADH remains as NADH when it is shuttled into the mitochondrion. Adding these numbers to the ATP made directly gives a total of 38 ATP produced from a molecule of glucose.Estimates of the actual number of ATP obtained by the cell are lower because of the costs of transporting ATP out of the mitochondria.

Glycogen

Glucose

Phosphoglyceraldehyde

Pyruvic Acid

Acetyl CoA

C6

C5

C4 TCAcycle

Glycerol

Lactic acid

Fatty Acids

FATS

Ketone bodies

Aminoacids Protein

Urea

Figure 5.17 The interconversion of glycogen, fat and protein

Figure 2.36. Oxidation of fatty acids The fatty acid (e.g., the 16-carbon saturated fatty acid palmitate) is initially joined to coenzyme A at the cost of one molecule of ATP. Oxidation of the fatty acid then proceeds by stepwise removal of two-carbon units as acetyl CoA, coupled to the formation of one molecule each of NADH and FADH2.

ATP Produced: 108 ATP

Amino Acid MetabolismTransamination- type of reaction in which the amine group is

transferred from one amino acid to form another

Oxidative Deamination- the metabolic pathway that removes amine groups from amino acids—leaving a keto acid and ammonia (which is converted to urea).

Essential amino acids- can not be produced by the body and must be obtained in the diet (lysine, tryptophan, phenylalanine, threonine, valine, methionine, leucine, isoleucine & histidine(children))

Nonessential amino acids- the body can produce them if provided with a sufficient amount of carbohydratesand the essential aas (aspartic acid, glutamic acid,proline, glycine, serine, alanine, cysteine, arginine, asparagine, glutamine, tyrosine)