Proteins

1. Proteins

2. What Are the Many Functions of Proteins? The word "protein"is derived from the Greek proteios, meaning "of first importance," and the scientists who named these compounds more than 100 years ago chose an appropriate term.

3. What Are Amino Acids? is an organic compound containing an amino group and a carboxyl group.

4. carboxyl group amino group a-carbon side chain Basic Amino Acid Structure • a-carbon is chiral (except for glycine) • at pH 7.0 uncharged amino acids are zwitterions • amino acids have a tetrahedral structure

7. we can classify amino acids into four groups, ● nonpolar, ●polar but neutral, ●acidic, and ●basic. Note that the non polar side chains are hydrophobic (they repel water), whereas polar but neutral, acidic, and basic side chains are hydrophilic(attracted to water).

10. Amino Acid Classification • Aliphatic • Aromatic • Sulfur containing • Polar/uncharged • basic/acidic • Hydrophobic Hydrophillic

11. Aliphatic (alkane) Amino Acids • Proline (pro, P)- cyclic “imino acid” • Glycine(gly, G)-only non-chiral amino acid, not hydrophobic • Alanine (ala, A) – R-group = methyl-group • Valine (Val, V) –Think V! • Leucine (Leu, L) – • Isoleucine (Ile, I) -2 chiral carbons Hydrophobicity

12. Aromatic Amino Acids • All very hydrophobic • All contain aromatic group • Absorb UV at 280 nm • Phenylalanine (Phe, F) • Tyrosine (Tyr, Y) – -OH ionizable (pKa = 10.5), H-Bonding • Tryptophan (Trp, W) – bicyclic indole ring, H-Bonding

13. Sulfur Containing Amino Acids • Methionine (Met, M) – “start” amino acid, very hydrophobic • Cysteine (Cys, C) – sulfur in form of sulfhydroyl, important in disulfide linkages, weak acid, can form hydrogen bonds.

14. Basic Amino Acids • Hydrophillic nitrogenous bases • Positively charged at physiological pH • Histidine – imidazole ring protonated/ionized, only amino acid that functions as buffer in physiol range. • Lysine - diamino acid, protonated at pH 7.0 • Arginine - guianidinium ion always protonated, most basic amino acid

15. Acidic Amino Acids • Contain carboxyl groups (weaker acids than a-carboxyl-group) • Negatively charged at physiological pH, present as conjugate bases (therefore –ate not –ic acids) • Carboxyl groups function as nucleophiles in some enzymatic reactions • Aspartate – • Glutamate –

16. Essential/Non-Essential Amino Acids • Essential –histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine • Non-essential – alanine, arginine*, aspartate, asparagine, cysteine*, glutamate, glutamine, glycine*, proline*, serine, tyrosine*

17. Polar Uncharged Amino Acids • Polar side groups, hydrophillic in nature, can form hydrogen bonds • Hydroxyls of Ser and Thr weakly ionizable • Serine (Ser, S) – looks like Ala w/ -OH • Threonine (Thr, T) – 2 chiral carbons • Asparagine (Asn, N) – amide of aspartic acid • Glutamine (Gln, Q) – amide of glutamic acid

18. Amino Acid Enantiomers • Steroisomers / enantiomers • Biological system only synthesize and use L-amino-acids

19. are chiralwith (carbon) stereocenters, • since R, H, COOH, and NHz are four different groups. • we can use glyceraldehyde as a reference point with amino acids.

21. What Are Zwitter ions? • Zwitterions: from the German word zwittel; meaning "hybrid." are compounds that have a positive charge on one atom and a negative charge on another Physical properties. ● solids with high melting points ● fairly soluble in water,

23. what happens if we change the pH of the solution ●adding a source of H30+, such as HCI solution(to lower the pH 2),Because H30+ is a stronger acid than a typical carboxylic acid , it donates a proton to the -COO- group, turning the zwitterion into a positive ion. ● a strong base, such asNaOH(to raise the pH 10). causes the - NH3 + to donate its proton to OH-, turning the zwitterion into a negative ion.

25. Isoelectric point (pI) pH at which all the molecules have equal positive and negative charges   • Every amino acid has a different isoelectric point, • Fifteen of the 20 amino acids have isoelectric points near 6. • the three basic amino acids have higher isoelectric points, and • the two acidic amino acids have lower values.

26. At or near the isoelectric point, amino acids exist in aqueous solution largely or entirely as zwitterions. • they react with either a strong acid, by taking a proton (the -COO- becomes -COOH), or • a strong base, by giving a proton (the -NH3+ becomes -NH2).

28. Amphiprotic a compound that is both an acid and a base. Buffer solution a solution that neutralizes both acid and base . • Amino acids are therefore amphiproticcompounds, and • aqueous solutions of them are buffers.

29. What Determines the Characteristics of Amino Acids? The side chain of an amino acid is responsible for the unique characteristics of these molecules. Ultimately, the functions of amino acids and their polymers, proteins, are determined by the side chains.

31. The dimer of cysteine, which is called cystine,the presence of cystine has important consequences for the chemical structure and shape of the protein molecules of which it is part. The bond is also called a disulfide bond. • Tow amino acids, glutamic acid and aspartic acid. Because of the presence of the carboxylate, the side chains of these two amino acids are negatively charged at neutral pH.

32. Three amino acids- histidine, lysine, and arginine have basic side chains. • In lysine, the side-chain amino group is attached to an aliphatic hydrocarbon tail. • In arginine, the side­ chain basic group, the guanidino group, is more complex in structure than the amino group, but it is also bonded to an aliphatic hydrocarbon tail.

33. The amino acids phenylalanine, tryptophan, and tyrosine have aromatic rings in their side chains. • these amino acids allow us to measure proteins because the aromatic rings absorb strongly at 280 nm and can be detected using a spectrophotometer. • These amino acids are also very important physiologically because they are both key precursors to neurotransmitters (substances involved in the transmission of nerve impulses). Tryptophan is converted to serotonin. Very low levels of serotonin are associated with depression, whereas extremely high levels produce a manic state. Manic-depressive schizophrenia can be managed by controlling the levels of serotonin and its further metabolites.

35. Tyrosine, itself normally derived from phenylalanine, is converted to the neurotransmitter class called catecholamines, which includes epinephrine, adrenalin. L-Dihydroxyphenylalanine (L-dopa) is an intermediate in the conversion of tyrosine. Lower than normal levels of L-dopa are involved in Parkin­son's disease. • Tyrosine and phenylalanine are precursors to norepinephrine and epinephrine. It causes the release of glucose and other nutrients into the blood and stimulates brain function.

37. What Are Uncommon Amino Acids? produced by modification of the parent amino acid after the protein is synthesized by the organism in a process called post-translational modification.

38. ●Hydroxyproline and hydroxylysine differ from their parent amino acids in that they have hydroxyl groups on their side chains; connective tissue proteins, such as collagen. ●Thyroxine differs from tyrosine in that it has an extra iodine-containing aromatic group on the side chain; thyroid gland, where it is formed by post-translational modification of tyrosine residues in the protein thyroglobulin. Thyroxine is then released as a hormone by proteolysis of thyroglobulin.

40. How Do Amino Acids Combine to Form Proteins? Each amino acid has a carboxyl group and an amino group. ● carboxylic acid and an amine could be combined to form an amide: The two amino acids are joined together by a peptide bond(also called a peptide linkage). The product is a dipeptide: (amide) the -COO- group of one amino acid molecule-say, glycine-can combine with the -NHa+ group of a second molecule-say, alanine:

42. Because it also contains a - COO- and an - NHa + group, we can continue the process to get a tetrapeptide, a pentapeptide, and so on, until we have a chain containing hundreds or even thousands of amino acids. These chains of amino acids are the proteinsthat serve so many important functions in living organisms.

44. Peptide Bond Formation

45. Partial double bond nature of peptide bond

46. Non-covalent forces important in determining protein structure • van der Waals: 0.4 - 4 kJ/mol • hydrogen bonds: 12-30 kJ/mol • ionic bonds: 20 kJ/mol • hydrophobic interactions: <40 kJ/mol

47. A word must be said about the terms used to describe these compounds. • ●The shortest chains are often simply called peptides, • ● longer ones are polypeptides, and still longer ones are proteins, that contains a minimum of 30 to 50 amino acids. • ●The amino acids in a chain are often called residues. • ● It is customary to use either the one-letter or the three-letter abbreviations.

48. Protein Nomenclature • Peptides 2 – 50 amino acids • Proteins >50 amino acids • Amino acid with free a-amino group is the amino-terminal or N-terminal residue • Amino acid with free a-carboxyl group is the carboxyl-terminal or C-terminal residue • Three letter code – Met-Gly-Glu-Thr-Arg-His • Single letter code – M-G-E-T-R-H

49. Protein Classification • One polypeptide chain - monomeric protein • More than one - multimeric protein • Homomultimer - one kind of chain • Heteromultimer - two or more different chains • (e.g. Hemoglobin is a heterotetramer. It has two alpha chains and two beta chains.)

50. Protein Classification • Simple – composed only of amino acid residues • Conjugated – contain prosthetic groups (metal ions, co-factors, lipids, carbohydrates) Example: Hemoglobin – Heme