Proteins

1. Proteins • The Function of Proteins • Amino Acids • The Peptide Bond • Structure of Proteins • Myoglobin, Hemoglobin and Oxygen • Overview of Protein Structure and Function • Effect of Temperature and pH

2. Proteins are among the “essential” compounds necessary for the normal functioning of a living system. • The name is derived from the Greek word “Proteios”, meaning first. • All proteins are made from amino acids.

3. The function of proteins • Enzymes Biological catalysts. • Antibodies They fight off infection. • Transport Move materials around • Ex. hemoglobin for O2. • Regulatory As hormones, they control metabolism. • Structural coverings and support • skin, tendons, hair, nails, bone. • Movement muscles, cilia, flagella.

4. Proteins are often gigantic in size • Insulin: Molecular Wt = 5700 • Hemoglobin: Molecular Wt = 64,000 • Virus Proteins: Molecular Wt = 40,000,000

5. Amino acids • All these proteins are made from the same building blocks. • Twenty common amino acids. • All are -amino acids except proline. • A primary amine is attached to the  carbon. • -carbon - the carbon just after the acid. • H • | • R-C-COOH • | • NH2

6. Amino acids • Because an acid and base are both present, an amino acid can form a +/- ion, called azwitterion. • H H • | | • R-C-COOH R-C-COO- • | | • NH2 NH3+ • How well it happens is based on pH and the type of amino acid.

7. -Amino acids • Except for glycine, the  carbon is attached to four different groups - it is a chiral center. • For Carbohydrates • We used the D-form. • For Amino Acids • We use the L-form. COO- | H3N - C - H | R + The amino group is on the left side of the fischer projection.

8. Classification of amino acids • The -amino acid group is the same in each of the amino acids. • They are classified by the polarity of the side chain (R). • Hydrophobic - water fearing • non-polar side chains • Hydrophilic - water loving • polar, neutral chains • negatively charged • positively charged

9. H | H-C-COO- | +NH3 H | CH3-C-COO- | +NH3 glycine alanine H3CH \ | HC-C-COO- / | H3C+NH3 H3C H \ | HC-CH2-C-COO- / | H3C+NH3 valine leucine Neutral, nonpolarside chains

10. H | CH3 -S-CH2-CH2-C-COO- | +NH3 methionine Neutral, nonpolarside chains H | -CH2-C-COO- | +NH3 H3C H || H3C-CH2-CH-C-COO- | +NH3 isoleucine phenylalanine proline H2C CH-COO- | | H2C+NH2 H2C

11. Polar, neutral amino acids H | HO-CH2-C-COO- | +NH3 HO H | | CH3-CH-C-COO- | +NH3 serine threonine tyrosine tryptophan H | -CH2-C-COO- | +NH3 H | CH2-C-COO- | +NH3 HO- N

12. Polar, neutral amino acids H | HS-CH2-C-COO- | +NH3 cysteine O H ||| H2N-C-CH2-CH2-C-COO- | +NH3 O H ||| H2N-C-CH2-C-COO- | +NH3 glutamine asparagine

13. Acidic, polar side chains • Based on having a pH of 7. O H ||| -O-C-CH2-CH2-C-COO- | +NH3 glutamic acid O H ||| -O-C-CH2-C-COO- | +NH3 aspartic acid

14. Basic, polar side chains • Based on a pH of 7. H +| H3N-CH2-CH2-CH2-CH2-C-COO- | +NH3 lysine +NH2 H || H2N-C-N-CH2-CH2-CH2-C-COO- | +NH3 arginine H | CH2-C-COO- | +NH3 histidine H N H N H +

15. Essential Amino Acids • Proteins are constantly being produced in the body for growth and repair. • Of the 20 amino acids found in these proteins, 10 cannot be synthesized by the body. • Arginine* Methionine • Histidine * Phenylalanine • Isoleucine Threonine • Leucine Tryptophan • Lysine Valine

16. Histidine is an essential amino acid for infants, but apparently not for adults. • Arginine is produced in the body but not in sufficient quantities to meet protein demand.

17. Complete or Adequate Proteins: supply all of the essential amino acids. (Animal Proteins) • Incomplete Proteins: Low in one or more of the essential amino acids (Vegetable Proteins) • Animal Proteins • Source Type of Protein Missing AA • Egg Complete None • Milk(Dairy) Complete None • Meat, fish Complete None

18. Vegetable Proteins • Source Type of Protein Missing AA • Wheat Incomplete Lysine • Corn Incomplete Lysine & • Tryptophan • Rice Incomplete Lysine • Beans Incomplete Methionine • Tryptophan • Peas Incomplete Methionine • Quinoa Complete • Hemp Complete

19. A complete assortment of amino acids can be obtained from a vegetable diet by pairing a vegetable protein missing one essential amino acid with a vegetable that contains it. • The two vegetable proteins are called complementary proteins. • Ex. Rice and Beans

20. Amphoteric Properties of Amino Acids • Amphoteric substances act as acids or bases. • They are acids when they donate protons. • They are bases when they accept protons. • Amino acids can act as acids or bases. • When placed in an acidic solution (low pH), they act as bases by accepting protons and becoming positively charged. • In basic solutions (high pH), they act as acids by donating protons and becoming negatively charged.

22. Amino Acids function asbuffers because they can neutralize small increases of acid or base. • Proteins are one of the major buffering systems in the body.

23. ISOELECTRIC POINT (pI) • A Zwitterion, which is electrically neutral overall, can only exist at a specific pH value. • This pH value, called the isoelectric point, is different for each amino acid. • Amino acids with hydrocarbon R groups attain their isoelectric point between pH 5.0 and 7.0 • ex. Leucine pH = 6.0 • Basic amino acids need high pH values to reach their isoelectric points. • ex. Arginine pH = 10.8

24. Acidic amino acids need low pH values. • ex. Aspartic acid pH = 3.0 • Proteins also have isoelectric points depending on the amino acids that make them up. • At their pH, proteins become insoluble in water, clump together, and precipitate out of solution.

25. H | H2NCCOOH | R H | H2NCCOOH | R’ H O | || H2N - C - C - | R H | N - C - COOH | | H R’ + The peptide bond • Proteins are polymers made up of amino acids. • Peptide bond - how the amino acids are • linked together to make a protein. This is a condensation reaction: H2O is eliminated.

26. This bond between the two amino acids is called a peptide bond. • Two amino acids joined like this give what is called a dipeptide. These 2 amino acids could also link the other way.

27. Any two amino acids can be joined in a similar manner to form dipeptides. • It doesn’t end here ! Each dipeptide still has a COOH and an NH2that can form new peptide bonds. • Adding a 3rd amino acid gives us a tripeptide. • This process can be continued to get a tetrapeptide, a pentapeptide, and so on until we have a chain of hundreds or even thousands of amino acids.

28. The chains of amino acids are the proteins. • The shorter chains are often called polypeptides. • Ex. Glucagon with 21 amino acids is a large polypeptide. • Insulin with 51 amino acids is a very small protein. • We will consider a protein to be a peptide chain with a minimum of 30 amino acids.

29. ala arg asn asp cys gln glu gly his ile leu lys met phe thr pro ser trp tyr val Primary structureof proteins • Primary Structure: What are the amino acids that make up the protein and how are they arranged in the chain ? (The amino acid sequence)

30. The amino acids in a chain are often referred to asresidues. • Ex. Ala-gly-lys3 residue amino acids • The amino acid residue with the free COOH group is called the C-terminal, and the amino acid residue with the free NH2 group is called the N-terminal. • Peptide and protein chains are always written with the N-terminal residue on the left.

31. H O | || H2N - C - C | R H O | || - NH - C - C - | R’ H | N - C - COOH | | H R’’ Peptides N-terminal residue C-terminal residue peptide linkages

32. The continuing pattern of peptide linkages is called the backboneof the protein molecule. The R groups are called the side chains. The 20 different amino acid side chains provide variety and determine the chemical and physical properties.

33. Each peptide and protein molecule in biological organisms has a different sequence of amino acids. • It is this sequence that allows the protein to carry out its function, whatever it might be. • Thenumber of different protein possibilities is staggering. • Ex. A tripeptide can have 20 different amino acids at each position. • 20 x 20 x 20 = 8000 possible tripeptides

34. A typical protein with 60 amino acid residues can have up to 2060different arrangements. • This means that there would be 1 x 1078 possibilities. • 1,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000, 000,000.

35. Secondary structureof proteins • Long chains of amino acids will commonly fold or curl into a regular repeating structure. • Structure is a result of hydrogen bonding between amino acids within the protein. • Common secondary structures are: •  - helix •  - pleated sheet • Secondary structure adds new properties to a protein like strength, flexibility, ...

36. -Helix One common type of secondary structure. Properties of -helix include strength and low solubility in water. Originally proposed by Pauling and Corey in 1951.

37. -Helix Every amide hydrogen and carbonyl oxygen is involved in a hydrogen bond. There are 3.6 amino acids in each turn. Multiple strands may entwine to make a protofibril. The R groups extend out from the helical portion of the -helix

38. -Helix example myosin head myosin tail ATP and actin binding sites thick filament thin filament actin myosin/actin structure Proteins used in muscle troponin

39. R | C R | C O || C O || C H | N H | N N | H C || O C || O N | H C | R C | R C | R R | C R | C O || C H | N O || C H | N N | H C || O C || O N | H C | R C | R C | R -Pleated sheets • Another secondary structure for protein. • Held together by hydrogen bonding between adjacent sheets of protein.

40. -Pleated sheets • Silk fibroin - main protein of silk is an example • of a  pleated sheet structure. Composed primarily of glycine and alanine. Stack like corrugated cardboard for extra strength.

41. Linus Pauling http://www.youtube.com/watch?v=yh9Cr5n21EE

42. Collagen • Family of related proteins. • About one third of all protein in humans. • Structural protein • Provides strength to bones, tendon, skin, blood vessels. • Forms triple helix - tropocollagen.

43. As an animal grows older, the extent of cross-linking increases and the meat gets tougher. • Treatment with boiling water converts collagen to gelatin. Therefore, cooking meat converts part of the tough connective tissue to gelatin, making the meat more tender. (ex. Stewing chickens)

44. Tanning hides increases the degree of cross-linking, converting skin to leather.

45. Wool, hair and muscle are all formed from strands of alpha helixes. • These proteins can be stretched because the hydrogen bonds can be elongated and then return to the original configuration. • This is especially true for wool.

46. DISULFIDE BRIDGES • Disulfide bridges are covalent bonds formed when 2 cysteine units are oxidized to form a cystine unit. SH SH S oxidation S reduction The strength of this bond is much greaterthan that of a hydrogen bond.

47. Fibrous proteins • insoluble in water • form used by connective tissues • silk, collagen, -keratins • Globular proteins • soluble in water • form used by cell proteins • 3-D structure - tertiary

48. Tertiary structure of proteins • This refers to how the molecule is folded. It makes the molecule very compact. • Results from interaction of side chains. • Protein folds into a tertiary structure. • This is typical of proteins called globular. • Found in egg and serum albumin, hemoglobin and myoglobin, and enzymes and antibodies.

49. Types of tertiary bonding • Possible side chain interactions: • - Similar solubilities • - Ionic attractions • - Attraction between + and - sidechains • - Covalent bonding

50. Sulfide Crosslink Hydrophobic interaction - S - S - -COO- H3N+- -O \ H -O \ H Hydrogen bonding Salt bridge Tertiary structureof proteins