General Biochemistry: Amino Acids and Peptide Bonds PDF

General Biochemistry Amino acids and peptide bond Sundus Shalabi, MD, PhD Faculty of Medicine [email protected] Outline Case scenario Amino acid side chains Nonpolar sidechains Aromatic side chains Polar uncharged Sulfur containin...

General Biochemistry Amino acids and peptide bond Sundus Shalabi, MD, PhD Faculty of Medicine [email protected] Outline Case scenario Amino acid side chains Nonpolar sidechains Aromatic side chains Polar uncharged Sulfur containing Charged polar Ionization of amino acids Titration curves for amino acids Peptide bond formation Case scenario  Nonpolar, aliphatic side chains Have non-polar side chains Tend to pack together rather than reacting with water. Display hydrophobic effect Glycine is the smallest AA. Achiral and can fit into hydrophobic or hydrophilic environments. Proline is special.. Contains a side group that is bound to the alpha C and the N. The five-membered ring makes it structurally restrictive.. Greatly affects the structure of proteins. Isoleucine has another chiral center Aromatic side chains Still considered hydrophobic. Phenylalanine contains an unreactive and highly non-polar aromatic ring. Tyrosine contains an aromatic ring with a hydroxyl group, making it less hydrophobic and more reactive. Tryptophan contains an indole group with the NH group, making it slightly reactive. Proteins can absorb light at UV light wavelength of 280 nm The aromatic R-groups in amino acids absorb ultraviolet light with an absorbance maximum in the range of 280nm. The ability of proteins to absorb ultraviolet light is predominantly due to the presence of the tryptophan which strongly absorbs ultraviolet light. A spectrophotometer  Serine and threonine both have hydroxyl group which makes them polar (hydrophilic) and reactive. Threonine has another chiral carbon Asparagine and glutamine contain polar carboxamide groups  Methionine is considered hydrophobic. Cysteine is polar.. Can form disulfide covalent bond  highly hydrophilic Lysine: has a relatively long side chain group ended by an amino group. positively charged at neutral pH. pKa=10. Arginine: also has a relatively long side chain. Terminal group is Guanidinium (resonance stabilized). positively charged at neutral pH. pKa=12.5 Histidine: has the imidazole group. Can exist in its protonated and deprotonated state at neutral pH. pKa=6.0 Aspartate and Glutamate: have a full negative charge on the carboxylate ion group at neutral pH (deprotonated). pKa=4.1 at low pH, it is protonated, and AA is called Aspartic acid and Glutamic acid respectively. Acidic Amino Acids and their Amides Back to the case: Question 1 Will S. has sickle cell anemia caused by a point mutation in his DNA that changes the sixth amino acid in the β-globin chain of hemoglobin from glutamate to valine. What difference would you expect to find in the chemical bonds formed by these two amino acids? Back to the case: Question 2 Is the substitution of a glutamate for a valine in sickle cell hemoglobin a conservative replacement? What about the substitution of an aspartate for a glutamate? Ionizable amino acids Each AA has an amino group and a carboxyl group that can lose/gain H+ ions as pH changes. Seven AA have ionizable side chain groups. At certain pH values, the ionizable side chain groups can exchange H+ ions. Participate in acid base reactions Form ionic bonds with other macromolecules At pH=pKa, half of the acid have deprotonated Ionizable amino acids Notes Active site of many enzymes Disulfide bridges. at basic pH, can form ionic bonds with positively charged ions. At neutral pH, neutral non-polar. Display hydrophobic effect,,, inside protein structure At neutral pH, polar positive, hydrophilic, ionic bonds with other molecules Amino acids have characteristic titration curves The isoelectric point (pI) is the pH value when the net charge of the amino acid is zero. Glycine has —COOH and NH+3 Amino acids have characteristic titration curves  Proteins are linear polymers of amino acids that are Peptide bond linked to one another by covalent bonds are amide bonds called peptide bonds. formation A condensation or dehydrolysis reaction. Dipeptide Back to the case Will S.’s hemoglobin, HbS, is composed of two normal α-chains and two β-globin chains with the sickle cell variant(α2β2S). This changes in amino acid composition from a glutamate to a valine in the β-chain Clinical scenario resolution