By: Quy Le (#6) URL: ://proteins1.tripod.com Organic Chem. 12 B Spring-2005 Proteins: Their Biochemistry and Functions.

By: Quy Le (#6) URL:  http://proteins1.tripod.com

Organic Chem. 12 BSpring-2005

Proteins: Their Proteins: Their Biochemistry and Biochemistry and

Functions.Functions.

OutlineOutlineI) History of proteinsI) History of proteins:: - Jöns Jacob Berzelius and Gerharus Johannes Mulder - Jöns Jacob Berzelius and Gerharus Johannes Mulder

coined the term “protein”.coined the term “protein”. - Investigation of proteins and their properties began - Investigation of proteins and their properties began

1800.1800.

II) Protein’s structureII) Protein’s structure:: - Many amino acid units link together to make up - Many amino acid units link together to make up

proteins.proteins. - Primary structure: the linear arrangement of amino - Primary structure: the linear arrangement of amino

acids.acids. - Secondary structure: areas of folding or coiling.- Secondary structure: areas of folding or coiling. - Tertiary structure: the final three-dimensional - Tertiary structure: the final three-dimensional

structure.structure. - Quaternary structure: non-covalent interactions.- Quaternary structure: non-covalent interactions.

III) Functions of Proteins:III) Functions of Proteins:

- Enzymes (catalytic activity & function)* - Enzymes (catalytic activity & function)* - Transport Proteins ( bind &carry ligands)* - Transport Proteins ( bind &carry ligands)* - Storage Proteins ( ovalbumin, gluten, ferreting) - Storage Proteins ( ovalbumin, gluten, ferreting) - Movement (muscles; can contract) - Movement (muscles; can contract)

- Mechanical support (collagen-bone, keratin)*- Mechanical support (collagen-bone, keratin)* - Defensive-protect ( antibodies, bacterial toxins) - Defensive-protect ( antibodies, bacterial toxins) - Regulatory-signal ( metabolic, hormones) - Regulatory-signal ( metabolic, hormones) - Receptors-detect stimuli ( membrane receptor, - Receptors-detect stimuli ( membrane receptor, and acetylcholine or insulin)* and acetylcholine or insulin)*

IV) Disease Related with Proteins:IV) Disease Related with Proteins:

- - Sickle cell diseaseSickle cell disease - - Marfan SyndromeMarfan Syndrome - Diabetes - Diabetes

I. History of Proteins.I. History of Proteins.

- It started from late 1700’s, Physiological - It started from late 1700’s, Physiological chemists was trying to understand the materials chemists was trying to understand the materials that made up living cells. They identified that made up living cells. They identified albuminoidsalbuminoids from coagulation of egg… from coagulation of egg…

- In 1800’s, Chemists set out to identify the - In 1800’s, Chemists set out to identify the chemical makeup of proteins (exp. Water= H2O; chemical makeup of proteins (exp. Water= H2O; Methane= CH4)Methane= CH4)

- By 1838, a Dutch chemist, Gerardus Mulder - By 1838, a Dutch chemist, Gerardus Mulder presented is finding that presented is finding that albuminoidsalbuminoids had had high high quantities ofquantities of nitrogen nitrogen and and smallsmall amounts of amounts of sulfursulfur..

http://www.madsci.org/posts/archives/feb98/888588800.Sh.r.htmlhttp://www.madsci.org/posts/archives/feb98/888588800.Sh.r.html

- July 10, 1838, a Swedish biochemist Jöns Jacob July 10, 1838, a Swedish biochemist Jöns Jacob Berzelius suggested Mulder to give the Berzelius suggested Mulder to give the albuminoidsalbuminoids more special name because it more special name because it appear to be a principal substance of animal appear to be a principal substance of animal nutritionnutritionthe word the word ProteinProtein (meaning of primary (meaning of primary importance) was used. importance) was used.

- In 1930s, the famous work of Moses Kunitz and - In 1930s, the famous work of Moses Kunitz and John Hward Northrop at the Institute in New John Hward Northrop at the Institute in New York City convinced the world; they studied York City convinced the world; they studied three three different chemical reactions came from different chemical reactions came from three different proteins.three different proteins.

-In 1953, Sanger’s experiments showed that -In 1953, Sanger’s experiments showed that proteinsproteins have have a unique amino acid sequencea unique amino acid sequence. He . He also showed for the first time that all also showed for the first time that all amino amino acids in mammalian proteinsacids in mammalian proteins are in the are in the S-S-configurationconfiguration, , peptide bondpeptide bond is an amide bond, is an amide bond, and amino acids haveand amino acids have alpha amino alpha amino groups and groups and alpha carboxyl groupsalpha carboxyl groups..

http://wiz2.pharm.wayne.edu/biochem/prot.htmlhttp://wiz2.pharm.wayne.edu/biochem/prot.html

II. Protein’s Structure:II. Protein’s Structure:

- Proteins are very complicated - Proteins are very complicated molecules. With 20 different molecules. With 20 different amino acids that can be amino acids that can be arranged in any order to arranged in any order to made a polypeptide of up to made a polypeptide of up to thousands of amino acids thousands of amino acids long.long.

http:// www.chembio.uoguelph.ca/educmat/phy456/gif/peptide5.gif

A. Structure of Amino Acids A. Structure of Amino Acids in Proteins:in Proteins:

- - Basic structureBasic structure::- All amino acids found in - All amino acids found in proteins have this basic proteins have this basic structure, differing only in structure, differing only in the structure of the R-the structure of the R-groupgroup

1. A alpha hydrogen: H1. A alpha hydrogen: H

2. A alpha amino group: -NH2 2. A alpha amino group: -NH2 (basic)(basic)

3. A alpha carboxyl group: -3. A alpha carboxyl group: -COOH (acidic)COOH (acidic)

4. A side chain: R (20 possible)4. A side chain: R (20 possible)

http://www.biology.arizona.edu/biochemistry/problem_sets/aa/aa.htmlhttp://www.biology.arizona.edu/biochemistry/problem_sets/aa/aa.html

B. Stereo Configuration of B. Stereo Configuration of Amino Acids.Amino Acids.

- All of the amino - All of the amino acids used in acids used in proteins (except proteins (except for glycine which for glycine which is not optically is not optically active) are of active) are of

L-configurationL-configuration..

- However in R/S - However in R/S notation Cysteine notation Cysteine is 2R, whereas the is 2R, whereas the others areothers are 2S 2S..

http://bmbiris.bmb.uga.edu/wampler/tutorial/aaconfig.htmlhttp://bmbiris.bmb.uga.edu/wampler/tutorial/aaconfig.html

C. Classifying of Amino C. Classifying of Amino AcidsAcids

- The 20 different - The 20 different R groups give R groups give amino acids amino acids individual individual characteristic. characteristic. They are They are grouped in grouped in four major four major groupsgroups according to according to their their characteristics.characteristics.

http://www.ucl.ac.uk/~sjjgsca/ProteinStructure.htmlhttp://www.ucl.ac.uk/~sjjgsca/ProteinStructure.html

D. Bonding in Amino D. Bonding in Amino AcidsAcids

- Polypeptides and - Polypeptides and proteins are formed of proteins are formed of chains of amino acids chains of amino acids joined together by joined together by linkages called linkages called peptide bonds.peptide bonds.

- Peptide bond - Peptide bond formation is an formation is an example of a example of a condensation condensation reactionreaction , whereas a , whereas a molecule of molecule of water is water is releasedreleased..

http://saints.css.edu/bio/schroeder/prothttp://saints.css.edu/bio/schroeder/proteins.htmleins.html

- - Peptide Bond Peptide Bond FormationFormation::

E. Primary Structure of E. Primary Structure of ProteinsProteins

- The primary structure - The primary structure of a protein is its of a protein is its linear linear sequence of sequence of amino acids and theamino acids and the disulfidedisulfide (-S-S-) (-S-S-) bridge; allbridge; all covalent covalent connection in a connection in a protein. protein.

- The amino terminal or - The amino terminal or ““N-terminalN-terminal”(NH3+) ”(NH3+) at one end; carboxyl at one end; carboxyl terminal “terminal “C-C-terminalterminal” (COO-) at ” (COO-) at the other end.the other end.

http://users.rcn.com/jkimball.ma.ultrhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Polypeptides.htanet/BiologyPages/P/Polypeptides.htmlml

F. Secondary Structure of F. Secondary Structure of ProteinsProteins

- - Alpha-helixAlpha-helix: described : described by Linus Pauling; has a by Linus Pauling; has a rod shaperod shape. The peptide . The peptide is coiled around like a is coiled around like a cylinder and stabilized cylinder and stabilized by by H-bonds formed H-bonds formed between peptidesbetween peptides

- - Beta-pleated sheetsBeta-pleated sheets: : adopt the conformation adopt the conformation of a of a sheet of papersheet of paper and and the structure is the structure is stabilized by stabilized by H-bonds H-bonds between amino in between amino in different polypeptidedifferent polypeptide strands. strands.

http://www.rothamsted.bbsrc.ac.uk/notehttp://www.rothamsted.bbsrc.ac.uk/notebook/courses/guide/prot.htm#IIbook/courses/guide/prot.htm#II

http://www.ekcsk12.org/science/apbihttp://www.ekcsk12.org/science/apbio/biochemnts.htmlo/biochemnts.html

G. Tertiary Structure of G. Tertiary Structure of ProteinsProteins

- Tertiary structure is the - Tertiary structure is the way the way the secondary secondary structure fold onto structure fold onto themselvesthemselves to form a to form a protein or a subunit of protein or a subunit of a more complex proteina more complex protein

- Amino acids which are - Amino acids which are very distant in the very distant in the primary structure primary structure might be close in the might be close in the tertiary one because of tertiary one because of the folding of the the folding of the chain.chain.

http://www.rothamsted.bbsrc.ac.uk/nothttp://www.rothamsted.bbsrc.ac.uk/notebook/courses/guide/prot.htm#IIebook/courses/guide/prot.htm#II

http://www.ekcsk12.org/science/apbihttp://www.ekcsk12.org/science/apbio/biochemnts.htmlo/biochemnts.html

H. Quaternary structure of H. Quaternary structure of ProteinsProteins

- Complexes of - Complexes of 2 or 2 or more polypeptidemore polypeptide chains held together by chains held together by noncovalentnoncovalent forces forces but in precise ratios but in precise ratios and with a precise 3-D and with a precise 3-D configuration.configuration.

- A good example is the - A good example is the quaternary structure of quaternary structure of hemoglobinhemoglobin, made up , made up of of 2 alpha and 2 beta2 alpha and 2 beta polypeptide chains.polypeptide chains.

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/Q/QuaternaryStructure.htmlhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/Q/QuaternaryStructure.html

http://www.ekcsk12.org/science/apbio/biochemnts.htmlhttp://www.ekcsk12.org/science/apbio/biochemnts.html

III. Function of ProteinsIII. Function of ProteinsA. Proteins as catalystA. Proteins as catalyst

- Proteins that act like - Proteins that act like catalystscatalysts in chemical in chemical reactions are called reactions are called enzymesenzymes..

- Enzymes are the catalysts which make possible - Enzymes are the catalysts which make possible biochemical reactions. Catalyst biochemical reactions. Catalyst increase the increase the raterate of a reaction, but are not themselves of a reaction, but are not themselves consumed or produced by the reaction.consumed or produced by the reaction.

- Enzymes are grouped into - Enzymes are grouped into six classessix classes according to the kind of reaction they catalyzeaccording to the kind of reaction they catalyze

http://courses.cm.utexas.edu/jrobertus/ch339k/overheads-2/ch8_enzyme-classes.jpg

B. ReceptorsB. Receptors- Proteins in the - Proteins in the Plasma Plasma

MembraneMembrane include: include: 1. 1. Transport channelTransport channel (D), (D),

which ions and which ions and macromolecules may macromolecules may passpass

2. 2. EnzymesEnzymes (I):(I): provide a provide a convenient surface for convenient surface for enzymes to be embedded.enzymes to be embedded.

3. 3. Cell surface receptors Cell surface receptors (B):(B): fit only to specific fit only to specific substances.substances.

4. 4. Cell surface identity Cell surface identity markers (E):markers (E): each cell each cell carries its own ID carries its own ID markers markers

5. 5. Cell adhesion proteins Cell adhesion proteins (A):(A): adjacent cells stick adjacent cells stick together via interlocking together via interlocking proteins on their proteins on their membranes.membranes.

http://ghs.gresham.k12.or.us/science/ps/sci/ibbio/cells/notes/ch6/ch6menu.htm

C. Transport Protein - C. Transport Protein - HemoglobinHemoglobin

- - HemoglobinHemoglobin is a is a protein that is carried protein that is carried by red cells. It by red cells. It picks up picks up oxygenoxygen in the lung and in the lung and delivers it to the tissues delivers it to the tissues to maintain the viability to maintain the viability of cell.of cell.

- Hemoglobin is made - Hemoglobin is made from two similar from two similar proteins that stick proteins that stick together. together.

http://www.chem.purdue.edu/chm333/hhttp://www.chem.purdue.edu/chm333/hemoglobin.JPGemoglobin.JPG

http://www.medical-http://www.medical-definitions.net/hemoglobin.htmdefinitions.net/hemoglobin.htm

D. Mechanical supportD. Mechanical support

- About one quarter of all of - About one quarter of all of the protein in our body is the protein in our body is collagen. collagen.

- - CollagenCollagen provides structure provides structure to our bodies, to our bodies, protecting protecting and supportingand supporting the softer the softer tissues and tissues and connectingconnecting them with the skeleton.them with the skeleton.

- Collagen is composed of 3 - Collagen is composed of 3 chains, wound together in a chains, wound together in a tight triple helixtight triple helix. Every . Every third amino acid is a glicine, third amino acid is a glicine, and many of the remaining and many of the remaining amino acids are proline or amino acids are proline or hydroxyproline.hydroxyproline.

http://www.rcsb.org/pdb/molecules/pdb4_1.htmlhttp://www.rcsb.org/pdb/molecules/pdb4_1.html

IV. Disease Related with IV. Disease Related with ProteinsProteins

A. Sickle Cell DiseaseA. Sickle Cell Disease- Sickle cell disease a - Sickle cell disease a

genetically disorder genetically disorder affecting 1out of 10 African affecting 1out of 10 African Americans.Americans.

- Disease is cause - Disease is cause by by mutation inmutation in the gene the gene responsible for the responsible for the production of hemoglobin. production of hemoglobin. SubstitutionSubstitution of a single of a single amino acid ( valine for amino acid ( valine for glutamic acid) in the glutamic acid) in the sixth sixth position ofposition of the B-chain of the B-chain of the hemoglobin molecule the hemoglobin molecule produces a hydrophobic.produces a hydrophobic.

- The defective hemoglobin - The defective hemoglobin forming long rods that forming long rods that stretch a red blood cell into stretch a red blood cell into a crescent too large to fir a crescent too large to fir through small blood vessels.through small blood vessels.

http://encarta.msn.com/media_681500788/Sickhttp://encarta.msn.com/media_681500788/Sickle-Cell_Anemia.htmlle-Cell_Anemia.htmlhttp://www.coe.neu.edu/research/berl/BEhttp://www.coe.neu.edu/research/berl/BERL_research_sicklecell.htmlRL_research_sicklecell.html

B. Marfan SyndromeB. Marfan Syndrome- Marfan syndrome is a heritable - Marfan syndrome is a heritable

(in 75%) disorder of connective (in 75%) disorder of connective tissue that tissue that affects many affects many organ systemsorgan systems including the including the skeleton, lung, eyes, heart and skeleton, lung, eyes, heart and blood vessels. Affect both men blood vessels. Affect both men and women, of any race and and women, of any race and ethnic group. They are typically ethnic group. They are typically very tall, slender, and loose very tall, slender, and loose jointedjointed

- In Marfan syndrome a protein - In Marfan syndrome a protein called fibrillin is deficient or called fibrillin is deficient or abnormal. Fibrillin is part of abnormal. Fibrillin is part of elastic fibres, accounting for elastic fibres, accounting for the unusual stretchiness and the unusual stretchiness and weakness of tissues.weakness of tissues.

- A mutation in the fibrillin gene - A mutation in the fibrillin gene on chromosome 15 is said to be on chromosome 15 is said to be responsible for the production responsible for the production of abnormal fibrillin molecules of abnormal fibrillin molecules which can’t function properly. which can’t function properly.

http://www.nlm.nih.gov/medlineplus/ency/imagepages/http://www.nlm.nih.gov/medlineplus/ency/imagepages/9611.htm9611.htmhttp://www.marfan.net.au/showcontent.toy?cid=1515http://www.marfan.net.au/showcontent.toy?cid=1515

C. DiabetesC. Diabetes- Diabetes occurs when - Diabetes occurs when

the body can't produce the body can't produce enough insulin, or when enough insulin, or when the insulin that the the insulin that the body makes does not body makes does not work properly.work properly.

- - Type 1 Diabetes:Type 1 Diabetes: because the insulin-because the insulin-producing cells of the producing cells of the pancreas are destroyed pancreas are destroyed by the immune system. by the immune system. People with type 1 People with type 1 diabetes diabetes produce no produce no insulininsulin and must and must insulin injection to insulin injection to control their blood control their blood glucose.glucose.

http://my.webmd.com/content/article/46/1667_http://my.webmd.com/content/article/46/1667_50911?src=pemedscape50911?src=pemedscape

Type 2 DiabetesType 2 Diabetes- People with type 2 diabetes - People with type 2 diabetes

produce insulin. However, produce insulin. However, the insulin their pancreas the insulin their pancreas secretes is either not secretes is either not enough or the body is enough or the body is unable to recognize and unable to recognize and use it properly. use it properly.

- When there isn’t enough - When there isn’t enough insulin or the insulin is insulin or the insulin is not used as it should be, not used as it should be, glucose can’t get into the glucose can’t get into the body’s cell.body’s cell.

- It affects 18 mill. - It affects 18 mill. Americans; usually occurs Americans; usually occurs in people over age 40 who in people over age 40 who are overweight.are overweight.

http://my.webmd.com/content/article/46/1667_50911?http://my.webmd.com/content/article/46/1667_50911?src=pemedscapesrc=pemedscape

ConclusionConclusion- Proteins are one of the classes of bio-- Proteins are one of the classes of bio-

macromolecules, that make up the macromolecules, that make up the primary constituents of living things.primary constituents of living things.

- They are essential to the structure and - They are essential to the structure and funstion of all living cells and viruses.funstion of all living cells and viruses.

- They are amongst the most actively - They are amongst the most actively studied molecule in biochemistry .studied molecule in biochemistry .

V. ReferencesV. References

- http://www.madsci.org/posts/archives/feb98/888588800.Sh.r.htmlhttp://www.madsci.org/posts/archives/feb98/888588800.Sh.r.html- http://wiz2.pharm.wayne.edu/biochem/prot.htmlhttp://wiz2.pharm.wayne.edu/biochem/prot.html

- http://www.chembio.uoguelph.ca/educmat/phy456/gif/peptide5.gif- http://www.biology.arizona.edu/biochemistry/problem_sets/aa/aa.htmlhttp://www.biology.arizona.edu/biochemistry/problem_sets/aa/aa.html

- http://bmbiris.bmb.uga.edu/wampler/tutorial/aaconfig.htmlhttp://bmbiris.bmb.uga.edu/wampler/tutorial/aaconfig.html- http://www.ucl.ac.uk/~sjjgsca/ProteinStructure.htmlhttp://www.ucl.ac.uk/~sjjgsca/ProteinStructure.html

- http://saints.css.edu/bio/schroeder/proteins.htmlhttp://saints.css.edu/bio/schroeder/proteins.html- http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Polypepthttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Polypept

ides.htmlides.html- http://www.ekcsk12.org/science/apbio/biochemnts.htmlhttp://www.ekcsk12.org/science/apbio/biochemnts.html- http://courses.cm.utexas.edu/jrobertus/ch339k/overheads-2/ch8_enzyme-classes.jpg- http://ghs.gresham.k12.or.us/science/ps/sci/ibbio/cells/notes/ch6/ch6menu.htm

- http://www.chem.purdue.edu/chm333/hemoglobin.JPGhttp://www.chem.purdue.edu/chm333/hemoglobin.JPG- http://www.rcsb.org/pdb/molecules/pdb4_1.htmlhttp://www.rcsb.org/pdb/molecules/pdb4_1.html

- http://www.coe.neu.edu/research/berl/BERL_research_sicklecell.hhttp://www.coe.neu.edu/research/berl/BERL_research_sicklecell.htmltml

- http://my.webmd.com/content/article/46/1667_50911?src=pemedscapehttp://my.webmd.com/content/article/46/1667_50911?src=pemedscape