Amino Acids Biochem 4511 Figures Essentials of Biochemistry 3rd Ed OSU Custom Edition Principles of Biochemistry 5th Ed Moran et al Lehninger Principles of Biochemistry 5th Ed Nelson Cox Fundamentals of Biochemistry 2nd Ed Voet Voet Pratt Amino Acids Carboxylic Acid Variable Group Amine Greek Lettering Alpha Beta Gamma Delta Epsilon Zeta Amino acids are Chiral Molecules A molecule that cannot be superimposed on its mirror image is chiral Amino Acids are Chiral All amino acids except for glycine are chiral All proteogenic amino acids are L stereoisomers L D system is historical in origin unlike S R system Optical Rotation of Glyceraldehyde Chiral molecules are optically active and rotate plane polarized light The L D nomenclature is based on the structure of L glyceraldehyde Levorotatory left L Dextrorotatory right D Amino Acid Stereochemistry Most naturally occurring amino acids have L stereochemistry D amino acids do exist in nature not in translated proteins but are less abundant and found in bacterial cell walls and natural products including antibiotics Fischer Projections Fischer projections are a convenient way of presenting three dimensional chemical structures in two dimensions Pioneered by Emil Fischer Horizontal groups project above the page Vertical groups project behind the page L L alanine Ala A H N 3 COO H COO 3N and D Isomers D alanine ala a H N 3 COO H COO 3N Use these projections for consistence and simplicity Amino Acids Contain Ionizable Groups Amino acids are ionizable and may be considered polyprotic Amino group pKa 9 5 Carboxyl group pKa 2 Several side chains are ionizable with variable pKa At physiological pH 7 4 amino acids bear a positively charged amine and a negatively charged carboxyl group Considering just the charged termini the net charge on an amino acid at pH 7 4 is zero Zwitterion Zwitterions pK1 pK2 pK values of free vs protein incorporated amino acids Titrating Alanine Alanine is amphoteric it can act as an acid or base 20 Common or Natural AAs 20 Common or Natural AAs A Ala Alanine F Phe Phenylalanine K Lys Lysine P Pro Proline T Thr Threonine Q Gln Glutamine V Val Valine C Cys Cysteine G Gly Glycine L Leu Leucine D Asp Aspartate H His Histidine M Met Methionine R Arg Arginine W Trp Tryptophan N Asn Asparagine S Ser Serine Y Tyr Tyrosine E Glu Glutamate I Ile Isoleucine H N 3 COO Naming the Amino Acids Asparagine was the first amino acid isolated from asparagus 1813 but it was not confirmed as an amino acid until 1932 Small Nonpolar Large Nonpolar Hydrophobic Correct structures Valine Val V Leucine Leu L Isoleucine Ile I Methionine Met M Incorrect structures Non zwitterionic form You will see it in papers it is formally correct but not physiologically relevant Proline Distinctive properties Secondary amine Constricted backbone Drawing hints 1 Draw cyclopentane 2 Add amine and carboxylate 3 Add the wedged bond Aromatic Amino Acids H3N COO Tyrosine H3N COO Phenylalanine Phe F Tyrosine Tyr Y Tyrosine side chain pKa 10 5 Phenylketonuria PKU Genetic disorder characterized by a mutation in the gene for the hepatic enzyme phenylalanine hydroxylase PAH PKU can lead to intellectual disability Treatment strict PHE restricted life long diet supplemented by amino acids and other nutrients Patients who are diagnosed early and maintain a strict diet can have a normal life span with normal mental development PAH Phenyl pyruvate detected in urine Tryptophan Tryptophan Trp W Serotonin 5 hydroxy tryptamine Precursor of Serotonin neurotransmitter happiness hormone Serotonin level is increased by several antidepressant drugs Some psychedelics are agonists of this molecule Aromatic AAs and UV Tyr and Trp absorb UV light at 280 nm Most proteins contain Tyr and or Trps Protein can be determined based on detection of Tyr Trp in proteins Both residues are also FLUORESCENT This can be used to probe conformational changes of unmodified proteins Practical Application UV Spectra Beer Lambert Law Beer s Law Absorbance c extinction coefficient of molecule 20 Common or Natural AAs Uncharged and Polar OH H3N COO Cysteine Ionization Free a a pKa 8 4 In Proteins pKa 6 8 2 7 Cysteine Cys C Oxidation of Cysteine Intracellular reduction potential maintained by glutathione see Pentose Phosphate Pathway PPP keeps cysteines reduced Disulfide X linking is typical for extracellular proteins e g Antibodies Cysteine Oxidation Curly vs Straight Hair Uncharged and Polar H2N O O NH2 H3N COO H3N COO Charged Side Chains Carboxylic Acids O NH2 H3N COO Asparagine Asn N Glutamate plays important role in a a metabolism transamination reactions Monosodium Glutamate is commonly used as a taste enhancer Ionizable Side Chains Carboxylic Acids Aspartate Asp D Aspartic Acid Asp D Asp pKa 3 9 Glu pKa 4 1 Glutamic Acid Glu E Glutamate Glu E Ionizable Side Chains Acidic Charged Side Chains Basic pKa 10 5 pKa 12 5 NH3 H2N NH2 NH H3N COO H3N COO Lysine Lysine side chain Hydrocarbon chain terminated by a point charge Classified as polar but some amphipathic character Lysine Lys K pKa 10 5 Arginine Arginine Arg R pKa 12 5 Charged Side Chains Basic pKa 6 0 Histidine pKa 6 0 6 6 1 in proteins What of the histidine side chain is ionized at pH 7 A 10pH pKa 10 7 6 10 HA pH 7 0 10 in positively charged form HA therefore a net positive charge Histidine pKa 6 0 6 6 1 in proteins Net charge 1 0 How to draw Histidine How NOT to draw Histidine Broken Resonance Amino Acid pKa Terminal carboxylate 2 3 5 Terminal amine 9 5 7 7 Asp Glu 4 His 6 6 6 Cys 8 4 6 8 Lys Tyr 10 5 Arg 12 5 Environment affects actual pKa values Neighboring charges Nonpolar environments Hydrogen bonding In enzyme active sites pKa often drastically different Branching Another way to categorize Valine Isoleucine Threonine Each of the above amino acids have two non hydrogen atoms connected to the carbon What a a is branched at the carbon 21st Amino Acid H H3N Se COO More active than S present in several metabolic enzymes How is it encoded in genome Reprogramming the UGA stop codontranslational recoding 22nd Amino Acid Know name at least Pyrrolysine Discovered at OSU by Dr Michael Chan and Dr Joseph Krzycki Figures from Chan lab web page Modified Amino Acids Phosphorylation pTyr pSer pThr Acetylation Lys Methylation 4 hydroxyproline Lys Arg Know which groups can go through which kind of modification MEMORIZE Your Amino Acids Names Codes Structures Properties What are the nonpolar amino acids What are the ionizable amino acids At any given pH what is the