Amino Acids PDF

Chapter II : Amino acids and proteins  Amino acids An amino acid is an acidic organic compound (COOH) containing an amine group (NH2) The most common amino acids are the α-amino acids COOH and NH2 groups are carried by the same carbon Basic building bl...

Chapter II : Amino acids and proteins  Amino acids An amino acid is an acidic organic compound (COOH) containing an amine group (NH2) The most common amino acids are the α-amino acids COOH and NH2 groups are carried by the same carbon Basic building blocks of proteins Only 20 α-amino acids are used to produce proteins Amino acids are amphoteric molecules: they can act as acids or bases  Structure of α-amino acids The α -amino acids (AA) have a common structural motif R :side chain. Variable part of aa α α - AA ➔ NH2 and COOH carried by the same C  Stereochemistry of α-amino acids Most amino acids are chiral molecules because they contain an asymmetric carbon This α-carbon (center of chirality) is linked to four different substituents: the amine function, the carboxyl function, a hydrogen atom and the group R Only glycine does not have an asymmetric carbon and is therefore not a chiral molecule  Optical isomerism ✓ The amino acids that make up proteins in humans belong to the L series ✓ Ex: For alanine we have two spatial conformations for the same amino acid (enantiomers) Mirror NH3 at NH3 at the left the right ✓ Amino acids of the D series are found in bacterial walls as well as in some peptides produced by bacteria  Classification of amino acids Amino acids are classified according to several criteria: 1. According to the chemical nature of the side chain ➔ 7 amino acid groups 2. According to the polarity of the side chain 3. According to their dietary importance 1. Classification according to the chemical nature of the side chain 7 groups of amino acids : Amino acids with aliphatic side chains (5) Amino acids with hydroxylated side chains (2) Amino acids with sulfur side chains (2) Amino acids with basic side chains (3) Amino acids with aromatic side chains (3) Amino acids with acidic side chains or amides (4) The imine acid (1) AA with aliphatic side chains Glycine Alanine Valine Gly [G] Ala [A] Val [V] Leucine Isoleucine Leu [L] Ile [I]  Glycine (G ou Gly) ✓ Simplest side chain, one hydrogen ✓ Classified as an aliphatic by default ✓ No asymmetric carbon ✓ Amino acid with the lowest molecular weight ✓ AA not essential in the human diet  Alanine (A ou ALA) ✓ Methylated side chain (CH3) ✓ AA not essential in the human diet  Valine (V ou VAL) ✓Isopropyl side chain ✓Essential AA in the human diet  Leucine (L ou LEU) ✓ Isobutyl side chain ✓ Essential AA in the human diet  Isoleucine (I ou ILE) ✓ Isobutyl side chain (C4H9) ✓ Isomer of Leucine (same chemical formula) ✓ Essential AA in the human diet AA with hydroxylated side chains Serine Threnonine Ser [S] Thr [T]  Serine (S ou SER) ✓ Side chain with hydroxyl group (OH) ✓ Phosphorylation site in many proteins ✓ Non-essential AA in the human diet  Threonine (T ou THR) ✓ Side chain with hydroxyl group (OH) ✓ Phosphorylation site in many proteins ✓ Essential AA in the human diet AA with sulfur side chains Cysteine Methionine Cys [C] Met [M]  Cysteine (C ou CYS) ✓Side chain with sulfhydryl group (Thiol: R-SH) ✓Amino acid forming disulfide bridges ✓AA not essential in the human diet  Methionine (M ou MET) ✓ Side chain with thioether group ✓ First amino acid in protein synthesis ✓ Essential AA in the human diet  AA with basic side chains Arginine Histidine Lysine Arg [R] His [H] Lys [K]  Histidine (H ou HIS) Imidazole side chain (aromatic) Essential AA in human food  Lysine (K ou LYS) - Amino side chain - Essential AA in the human diet  Arginine (R ou ARG) Guanidine group at the end of the side chain Always charged at physiological pH Essential AA in the human diet AA with aromatic side chains Phenylalanine Tyrosine Tryptophane Phe [P] Tyr [Y] Trp [W]  Phenylalanine (F ou PHE) Aromatic side chain (Phenyl) Light absorption in the UV around 280nm One of the most hydrophobic amino acids Essential AA in the human diet  Tyrosine (Y ou TYR) Aromatic side chain (Phenol) Light absorption in the UV around 280nm Phosphorylation site in many proteins Non essential AA in human food  Tryptophane (W ou TRP) Aromatic side chain (Indol) Absorption of light in the UV towards 280nm Essential AA in the human diet AA with acid or amide side chains Aspartic acid Glutamic acid Aspargine Asp [Asp] Glu [E] Asn [N] Glutamine Gln [Q]  Aspartic Acid (D ou ASP) Acidic side chain AA not essential in the human diet  Glutamic acid (E or GLU) Acidic side chain AA not essential in the human diet  Asparagine (N ou ASN) Side chain with amide group AA not essential in the human diet  Glutamine (Q ou GLN) Side chain with amide group Most abundant amino acid in the blood AA not essential in the human diet  Imine acid Proline Pro [P] Only AA with a bond between R and NH2 ➔ Cyclic side chain AA not essential in the human diet 2. Classification according to the polarity of the side chain 1. Amino acids with non-polar (hydrophobic) R groups 2. Amino acids with uncharged polar groups (hydrophilic) 3. Amino acids with polar groups charged (hydrophilic) : - negatively (acidic) - positively (basic)  Non-polar amino acids:  Uncharged polar amino acids :  Charged polar amino acids: Negatively Positively Acidic side chains Basic side chains 3. Classification of amino acids according to their dietary importance ✓ Essential amino acids: must be provided by the diet: - valine, leucine, isoleucine, phenylalanine, tryptophan, methionine, threonine, lysine, + histidine (essential for children), and arginine (semi-essential) ✓ Non-essential amino acids: - glycine, alanine, proline, serine, cysteine, tyrosine, asparagine, glutamine, aspartic acid, glutamic acid.  Zwitterions ✓ An amino acid contains a -COOH group and an -NH2 group ✓ In aqueous solution and at a specific pH, the -COOH group loses a proton and is almost entirely in the -COO- form and the NH2 group picks up a proton and is in the NH3+ form ➔ the structure of the amino acid becomes: Zwitterions Here uncharged side chain  Zwitterions ✓ Compounds that have an equal number of positive and negative charges and therefore have no net charge are called Zwitterions General theoretical structure that does not exist in reality Zwitterionic form  Isoelectric pH (pHi) ✓ Amino acids are amphoteric molecules: they can act as acids or bases ✓ A zwitterion is characterized by an isoelectric pH (pHi) for which the charges balance and the net charge is zero dipolar ion to the very acidic pH zone zwitterion to the highly alkaline pH zone pH < pHi (acidc pH) pH = pHi pH > pHi (basic pH) Total charge The amino acid behaves as a =0 The amino acid behaves as cation (+ charged ) and an anion (- charged ) and migrates to the cathode (-) migrates to the anode (+)  Determination of pKa a. Amino acids with uncharged side chains Amino acids with non-ionizable side chains are characterized by two ionization constants pKa1 (α- COOH) and pKa2 (α-NH3+) pKa1 pKa2  Courbe de titration le la glycine Example 1 Weak acid : pH= pKa + log [A-]/[AH] [NH2]=[NH3+] 50% NH3+ et 50%NH2 pH=pKa + log 1 Weak base pH=pK2 pH= pKa + log [B]/[BH+] [COO-]=[COOH] Inflection point: 50% COO- et 50% COOH - the elimination pH=pKa + log 1 of the first proton pH=pKa1 is complete 100% COO- ➔ no COOH  Titration curve of alanine Example 2 Cation NH2CHRCOO- Anion Zwitterion NH3+CHRCOOH (Z) Cation b. Amino acids with charged side chains Example of glutamic acid pKa1 pKR pKa2 Glutamate titration curve pK2=9,67 pKR= 4,25 pK1= 2,19  Calculation of the pHi The pHi is the pH halfway between the pKa values for the ionizations located on either side of the isoelectric state Isoelectric pH (pI) = (pK1 + pK2) /2 1- Amino acid with uncharged side chain Ex : Alanine : pKa1 = 2,35 pKa2 = 9,69 pH H3+N -CH-COOH H3+N -CH-COO- H2N -CH-COO- CH3 CH3 CH3 Isoelectric pH (pI) = (pK1 + pK2) /2 = 2,35+9,69/2=6,02  Calculation of pHi 2- Amino acid with a charged side chain Ex : lysine pK1=2,18 pK2=8,95 pK3=10,79 Isoelectric form pHi = (pK2+pK3)/2 = 1/2 (8, 95+ 10,79) ≈9,87  Absorbances of aa: ✓ Amino acid solutions are colorless ✓ Most amino acids absorb at a wavelength