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 Proteins and Amino Acids Amino Acids Carboxylic Acid Amine 20 unique variable groups define the 20 common amino acids Greek Lettering a Alpha Beta Gamma Delta Epsilon z Zeta Amino Acids are Chiral All amino acids except for glycine are chiral L D system is historical in origin Chiral Molecules A molecule that cannot be superimposed on its mirror image is chiral antonym achiral Optical Rotation of Glyceraldehyde Extra Chiral molecules are optically active and rotate plane polarized light L glyceraldehyde The L D nomenclature is based on the structure of Optical Rotation of Glyceraldehyde Extra L Glyceraldehyde D 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 but often and found in bacterial cell walls and natural products including antibiotics Amino Acid Chirality Based on the organic chemistry R S system most naturally occurring chiral amino acids have S stereochemistry except cysteine Biochemists use the L D system to describe amino acid stereochemistry independent of side chain identity The 20 common chiral amino acids have L stereochemistry Is Chirality Important 1960s given as anti nausea to pregnant women teratogen Structures with small chirality mistakes are WRONG 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 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 Titrating Alanine Alanine is amphoteric it can act as an acid or base pI Isoelectric Point pI or Isoelectric point pH where molecule carries no net charge pH where the number of positive and negative charges are equal pI 1 2 pKi pKj Where i and j are transitions of the neutral species Context and pKa Extra Proteins and peptides Still a Zwitterion 20 Common or Natural AAs A Ala Alanine F Phe Phenylalanine K Lys Lysine P Pro Proline T Thr Threonine C Cys Cysteine G Gly Glycine L Leu Leucine Q Gln Glutamine V Val Valine D Asp Aspartate H His Histidine M Met Methionine R Arg Arginine W Trp Tryptophan E Glu Glutamate I Ile Isoleucine N Asn Asparagine S Ser Serine Y Tyr Tyrosine H3NCOO Large Nonpolar Hydrophobic Small Nonpolar Proline Distinctive properties Secondary amine Constricted backbone Drawing hints 1 Draw cyclopentane 2 Add amine and carboxylic acid 3 Add the wedged bond Aromatics Phenylalanine Ball Stick Space Filling CPK Tyrosine Phenylalanine Phe F Tyrosine Tyr Y Tyrosine side chain pKa 10 5 Tyrosine Hydrogen bonding capability Some polar some nonpolar characteristics Tryptophan Why can t you easily protonate the Trp side chain Tryptophan Trp W UV Spectra Beer Lambert Law Beer s Law Absorbance c extinction coefficient of molecule Aromatic AAs and UV Protein can be determined based on Trp and Tyr in solution Uncharged and Polar Cysteine C Cys Cysteine Ionization pKa 8 4 Cysteine Cys C Cysteine Chirality 2 1 3 3 1 2 L Cysteine L Threonine Cysteine at Carbon Threonine at Carbon 1 N H 2 C S H 3 C O O 1 N H 2 C O O 3 C O C H Oxidation of Cysteine Reduced Oxidized Disulfide bond Cystine Cysteine Oxidation Curly vs Straight Hair Uncharged and Polar Charged side Chains Acidic Asparagine Asn N Sidenote MSG umami Ionizable Side Chains Acidic Aspartic Acid Asp D Aspartate Asp D Asp pKa Glu pKa 4 1 Glutamic Acid Glu E Glutamate Glu E Charged Side Chains Basic pKa 10 5 pKa 6 0 pKa 12 5 Lysine Lysine side chain Hydrocarbon chain terminated by a point charge Classified as polar but some amphipathic character Amine can be nucleophile esp when deprotonated Lysine Lys K pKa 10 5 Side Chain Groups Arginine Histidine Arginine Arginine Arg R pKa 12 5 How NOT to Draw Arginine Correct Improper resonance structures Incorrect chemical structures especially common with charge delocalization Histidine pKa 6 0 What of the histidine side chain is ionized at pH 7 A HA 10pH pKa 10 7 6 10 pH 7 0 10 in positively charged form HA therefore a net positive charge Histidine pKa 6 0 Net charge 1 0 How to draw Histidine How NOT to draw Histidine Broken Resonance Amino Acid pKa Terminal carboxylate 2 Terminal amine 9 5 Asp Glu 4 His 6 Cys 8 4 Lys Tyr 10 5 Arg 12 5 Environment affects actual pKa values Neighboring charges Nonpolar environments Hydrogen bonding In enzyme active sites often drastically different 21st Amino Acid H3NCOO HSe 22nd Amino Acid Discovered at OSU by Dr Michael Chan and Dr Joseph Krzycki Figures courtesy Michael Chan Modified Amino Acids Phosphorylation pTyr pSer pThr Acetylation Lys Methylation Lys Arg 4 hydroxyproline MEMORIZE YOUR AA s Names Codes Structures Properties What are the nonpolar amino acids What are the ionizable amino acids At any given pH what is the predominant ionization state Which amino acids have planar side chains Which amino acids have 2 chiral centers No chiral centers