Amino acids, peptides, and proteins

1. Amino acids, peptides, and proteins Dr. Mamoun Ahram Nursing Summer semester, 2016

2. General structure • Proteins are polymers of α-amino acids (or amino acids). • An amino acid consists of • a central carbon atom, called the  carbon, linked to four groups • an amino group (-NH2), • a carboxylic acid group (-COOH), • a hydrogen atom, and • a specific R group (the side chain)

3. L and D isomers • With four different groups connected to the tetrahedral α-carbon atom, amino acids can be present in two forms that are mirror-images of each other (they are enantiomers). • They are called L isomer and D isomer. • Amino acids with their two isomers are said to be chiral (when a central carbon is bonded to four different groups). • The presence of one chiral carbon atom always produces a chiral molecule that exists in mirror-image forms. Only L amino acids naturally make up proteins.

5. Types of amino acids • There are twenty kinds of amino acids depending on the side chains varying in: • size • Shape • Charge • hydrogen-bonding capacity • hydrophobic character • chemical reactivity

7. Non-polar, aliphatic amino acids

8. Glycine • The simplest one is glycine, which has just a hydrogen atom as its side chain. • With two hydrogen atoms bonded to the -carbon atom, glycine is unique in being achiral (not chiral).

9. Alanine • Alanine, the next simplest amino acid, has a methyl group (-CH3) as its side chain.

10. Valine, leucine, and isoleucine • Larger hydrocarbon side chains are found in valine, leucine, and isoleucine.

11. Methionine • Methionine contains an aliphatic side chain that includes a thioether (-S-) group. Thioether Ether

12. Proline • Proline also has an aliphatic side chain, but is bonded to both the nitrogen and the -carbon atoms. • The ring structure of proline makes it more rigid than the other amino acids. -nitrogen

13. Phenylalanine and Tryptophan • Phenylalanine contains a phenyl ring. • Tryptophan has an indole ring; the indole group consists of two fused rings and an NH group.

14. Positively-charged amino acids

15. Lysine and arginine • Lysine and arginine have relatively long side chains that terminate with groups that are positively charged at neutral pH. • Lysine ends with a primary amino group and arginine by a guanidinium group.

16. Histidine • Histidine contains an imidazole group, an aromatic ring that also can be positively charged.

17. Negatively-charged amino acids

18. Aspartic acid and glutamic acid • Two amino acids contain acidic side chains: aspartic acid and glutamic acid. • These amino acids are often called aspartate and glutamate when they are charged.

19. Polar amino acids

20. serine and threonine • Serine and threonine, contain aliphatic hydroxyl groups. • The hydroxyl groups on serine and threonine make them hydrophilic and reactive.

21. Cysteine • Cysteine contains a sulfhydryl or thiol (-SH), group. The sulfhydryl group is reactive.

22. Asparagine and glutamine • Asparagine and glutamine are uncharged derivatives of aspartate and glutamate. • Each contains a terminal carboxamide in place of a carboxylic acid. carboxamide

23. Tyrosine • The aromatic ring of tyrosine contains a hydroxyl group. This hydroxyl group is reactive.

24. Amino acids are often designated by either a three-letter abbreviation.

25. Ionization of amino acids

26. Why do amino acids get ionized? • Amino acids can become ionized since the carboxyl group and amino group can become protonated (gain a proton) and unprotonated (lose a proton). • Therefore, they can act as acids or bases. Such molecules are said to be amphoteric.

27. Effect of pH • The ionization state of an amino acid varies with pH since each group has its own pKa. • Amino acids at physiological pH (pH 7.4) exist as dipolar ions where the carboxyl group is unprotonated (-COO-) and the amino group is protonated (-NH3+). • In acid solution (e.g., pH 1), the amino group is protonated (-NH3+) and the carboxyl group is not (-COOH). • As the pH is raised, the carboxylic acid gives up a proton. • The dipolar form persists until the pH approaches 9, when the protonated amino group loses a proton.

28. Zwitterion and isoelectric point • Even though this amino acid is charged, it is electrically neutral. • Such a molecule with two opposite charges and a net charge of zero is termed a zwitterion. • The pH where the net charge of a molecules such as an amino acid or protein is zero is known as isoelectric point or pI.

29. Ionization of side chains • Nine of the 20 amino acids have ionizable side chains. • These amino acids are tyrosine, cysteine, arginine, lysine, histidine, serine, threonine, aspartic and glutamic acids. • Each side chain has its own pKa values for ionization of the side chains. • At neutral pH • aspartic acid and glutamic acid are negatively charged. • Arginine and lysine are positively charged.

30. Histidine • An important amino acid in the function of many proteins and enzymes in terms of its pKa is histidine. • With a pKa value near 6, the imidazole group can be uncharged or positively charged near neutral pH.

31. Glutamate (same for Asp) Total charges: +1 0 -1 -2 pH < 2 pH = 3 9> pH > 4 pH > 10

32. Lysine (similar to arginine) Total charges: +2 0 -1 +1 pH < 2 9> pH > 3 pH > 10 pH > 11

33. Note • You need to know the names of amino acids, the special structural features of amino acids, their abbreviations or designations, the pKa of groups (not exact numbers, but which ones are acidic, basic, or near neutral).

34. Essential amino acids • There are nine amino acids that are essential. • Essential nutrients are those not made by the human body in significant amounts and must be derived from diet • These are: Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, and Valine. • The other 11 amino acids are non-essential amino acids.

35. Polypeptides and protein structure

36. Four Levels of Protein structure • The primary structure of a protein is the sequence of amino acid residues that constitute the polypeptide chain. • Secondary structure refers to the localized organization of parts of a polypeptide chain. • Tertiary structure refers to the three-dimensional structure of a polypeptide chain, that is, the three-dimensional arrangement of all the amino acids residues. • Some proteins are made of multiple polypeptides crosslinked (connected) with each other. These are known as multimeric proteins. • Quaternary structure describes the number and relative positions of the subunits in a multimeric protein.

38. Primary structure

39. Peptide bond • Proteins are linear polymers formed by covalently linking the α-carboxyl group of one amino acid to the α-amino group of another amino acid with a peptide bond (also called an amide bond).

40. A condensation reaction • The formation of a dipeptide from two amino acids is accompanied by the loss of a water molecule in a condensation reaction that is energetically unfavorable.

41. Definitions • The short chain of amino acids is known as an oligopeptides or just peptide. • Each amino acid unit in a polypeptide is called a residue Longer peptides are referred to as polypeptides. • Peptides generally contain fewer than 20-30 amino acid residues, whereas polypeptides contain as many as 4000 residues. • Polypeptide chains that have organized three-dimensional structures are referred to as proteins .

42. Directionality of reading • A polypeptide chain has polarity because its ends are different, with an α-amino group at one end and an α-carboxyl group at the other. • The amino end is the beginning of a polypeptide chain.

43. Backbone and side chains • A polypeptide chain consists of a regularly repeating part, called the main chain or backbone, and a variable part, comprising the distinctive side chains.

44. Features of the backbone • The backbone is made of the α-amide N, the α C, and the α carbonyl C atoms. • The polypeptide backbone is rich in hydrogen-bonding (an exception is proline, which has an NH group, but not C=O). • It has a zig-zag structure and is planar. • It has a double bond character rigid, and charged.

45. Importance of peptide bond • The primary structure of a protein determines the other levels of structure. • A single amino acid substitution can give rise to a malfunctioning protein, as is the case with sickle-cell anemia.

46. Sickle cell hemoglobin (HbS) • It is caused by a change of amino acids in the 6th position of  globin (Glu to Val). • The mutation results in: 1) arrays of aggregates of hemoglobin molecules, 2) deformation of the red blood cell, and 3) clotting in blood vessels and tissues.

47. How is protein structure determined? • The folding of a protein chain is determined by many different sets of weak noncovalent bonds that form between one part of the chain and another. • These involve atoms in the polypeptide backbone, but mainly by atoms in the amino acid side chains.

48. Hydrogen bonds • Polypeptides contain numerous proton donors and acceptors both in their backbone and in the R-groups of the amino acids.

49. Electrostatic interactions • These include charge-charge interactions between oppositely charged R-groups of amino acids such as lysine or arginine and aspartic acid or glutamic acid. These are also known as salt bridges.

50. van der Waals attractions • Although van der Waals forces are extremely weak, it is the huge number of such interactions that occur in large protein molecules that make them significant to the folding of proteins.