Amino Acids Proteins are composed of 20 common amino acids Each amino acid contains: (1) Carboxylate group (2) Amino group (3) Side chain unique to each amino acid Drawn at very acidic pH (pH=1)

Amino Acids (pg 29 v7) (1) Hydrophobic (non polar) (2) polar uncharged (3) positively charged (4) negatively charged (5) aromatic

Stereochemistry of amino acids 19 of the 20 common amino acids have a chiral  -carbon atom (Gly does not) Threonine and isoleucine have 2 chiral carbons each Mirror image pairs of amino acids are designated L (levo) and D (dextro) Proteins are assembled from L-amino acids (a few D-amino acids occur in nature)

4 Two amino acids (Thr, Ile) also have a chiral C atoms in their sidechains (R). Which carbon’s are chiral in Isoleucine? **** = R

1. Which statement is NOT correct about classification of amino acids? A) alanine and valine are neutral, nonpolar amino acids B) lysine and arginine are basic amino acids C) tryptophan and phenylalanine are aromatic amino acids D) aspartic acid and asparagine are acidic amino acids E) alanine and isoleucine are aliphatic amino acids 2. Which of the following amino acids is the LEAST water soluble at pH 7.0? WHY? A) tryptophan B) glutamic acid C) tyrosine D) histidine E) lysine Amino Acid Problems : :

1. Which statement is NOT correct about classification of amino acids? A) alanine and valine are neutral, nonpolar amino acids B) lysine and arginine are basic amino acids C) tryptophan and phenylalanine are aromatic amino acids D) aspartic acid and asparagine are acidic amino acids E) alanine and isoleucine are aliphatic amino acids 2. Which of the following amino acids is the LEAST water soluble at pH 7.0? WHY? A) tryptophan B) glutamic acid C) tyrosine D) histidine E) lysine Amino Acid Problems : :

4. Which of the following is NOT a biological role of amino acids? A) primary energy carrier molecules within cells B) components of proteins C) components of peptide hormones D) biological buffers E) all of the other choices are biological uses of amino acids Amino Acid Problems 3. Which of the following groups in a protein CANNOT form Hydrogen-bonds with an Arginine sidechain at pH 7? Why? A) Aspartate B) Glutamate C) Terminal carboxylate D) Mainchain (backbone) carbonyl E) Lysine

4. Which of the following is NOT a biological role of amino acids? A) primary energy carrier molecules within cells ATP B) components of proteins C) components of peptide hormones D) biological buffers E) all of the other choices are biological uses of amino acids Amino Acid Problems 3. Which of the following groups in a protein CANNOT form Hydrogen-bonds with an Arginine sidechain at pH 7? Why? A) Aspartate B) Glutamate C) Terminal carboxylate D) Mainchain (backbone) carbonyl E) Lysine also a donor

R Are the amino and carboxy termini the only ionizable groups in amino acids? No pKaR!!! Ionization state of an Amino Acid Depends on pH

Predominant form Predominant form Predominant form at pH = 1 at pH = 7 at pH =

Titration of the Amino Acid Alanine A = B = C = all C fully protonated all A fully deprotonated all B neutral species [C] = [B] [B] = [A] 3) At what pH is the net charge zero species at a maximum? What is the Net charge of each species?

pK 1 = 2.4 pK 2 = 9.8 pI = (pK 1 + pK 2 ) / 2 pK R = sidechain if ionizable pI is the pH at which an amino acid is electrically neutral pI is the pH at which the average net charge of amino acid is zero Isoelectric Point (pI) of an Amino Acid For an amino acid without an ionizable sidechain (2 pKa’s), the pI occurs half-way between the two acid dissociation constants (pK a ) values: pK 1 = 2.4 pK 2 = 9.8

Several of the amino acids have ionizable sidechains, (3 pKa’s) Glutamic acid The pI calculation is more complicated by the presence of three (3) ionizable groups in one amino acid (triprotic acid)  First assign pK a s given to the correct functional groups: Effect of Sidechain Functional Group on Amino Acid’s pI

Acid-Base Properties of Glutamic Acid At what pH range is the charge of Glu closest to zero? Or at what pH range will Glu be present predominantly in the form shown to the right?

Glu: the pI is given by the average of the pK a values of the two COOH groups which ionize on either side of the neutral species: For amino acids with three ionizable groups, either polar charged ones His, Lys, Arg, Glu, and Asp) or Cys, Tyr, pI reflects the chemical nature of the sidechain R group. pI = (pK 1 +pK R )/ Isoelectric Point (pI) of Glutamic Acid Net Charge?

Nonpolar amino acids: pI is near 7 (neutral pH) 2) Acidic amino acids (RCOOH groups in sidechain): cellular pH ~7 the sidechain carboxy group is deprotonated and can act as a BASE 3) Basic amino acids (RNH 3 + groups in sidechain): cellular pH ~7 the sidechain amino groups are protonated and can act as a ACID pI represents the collective “pK a ” of the entire molecule pI = (pK N + pK C ) / 2 pI = (pK C + pK R ) / 2 pI = (pK N + pK R ) / 2

Forming Biological Molecules dehydration synthesis: formation of large molecules by the removal of water -monomers are joined to form polymers

Breaking Biological Molecules hydrolysis: breakdown of large molecules by the addition of water -polymers are broken down to monomers

Peptides! Lue-enkephalin: pentapeptide endorphin bind to opioid receptor; regulate pain Tyr-Gly-Gly-Phe-Leu YGGFL H3N+H3N+ -

Water molecules interact with polar side chains to form a hydration layer containing 0.3g water per gram of protein, about two waters for every amino acid residue. This bound hydration layer has different properties to bulk water. The density is 10% higher and it has a 15% greater heat capacity suggesting much reduced molecular motion. Properties of polypeptides in solution