Biomolecules: Amino Acids PDF

BIOMOLECULES: NIKKI GIGI LEGASPI RMT, AMINO ACIDS MD  LEARNING OBJECTIVES FOR TODAY 1. Diagram the structures and write the three and one-letter designations of the 20 amino acids 2. Describe the importance and contribution of the R-group 3. Define Isoelectric pH and explain its relatio...

BIOMOLECULES: NIKKI GIGI LEGASPI RMT, AMINO ACIDS MD  LEARNING OBJECTIVES FOR TODAY 1. Diagram the structures and write the three and one-letter designations of the 20 amino acids 2. Describe the importance and contribution of the R-group 3. Define Isoelectric pH and explain its relationship to the net charge on a polyfunctional electrolyte 4. Describe the directionality, nomenclature and primary structure of peptides 5. Describe the conformational consequences of the partial double-bond character of a peptide bond and identify the bonds in the peptide backbone that are free to rotate PROTEINS Most abundant and functionally diverse molecules in living systems Linear polymers of amino acids Why are Proteins important? Ezymes regulate metabolism Neurotransmitters Contractile proteins of muscles Connective tissue framework Transport of molecules in blood Components of immune system WHAT IS PROTEOME AND PROTEOMICS? Proteome – set of ALL PROTEINS expressed by an individual cell at a particular time Proteomics – study that aims to identify the entire complement of proteins elaborated by a cell under diverse conditions  AMINO ACIDS More than 300 amino acids have been described but only 20 are commonly found in mammalian proteins These are the only amino acids coded by the DNA CENTRAL DOGMA OF MOLECULAR BIOLOGY GENETIC CODE  AMINO ACIDS Each amino acid has the same fundamental structure: a central carbon atom (also known as the alpha carbon), an amino group (NH2), a carboxyl group (COOH) and a hydrogen atom In an aqueous solution, both amino and carboxyl group are ionized Every amino acid also has another atom or group of atoms bonded to the central carbon known as the R group. This R group or side chain TYPES OF AMINO ACIDS 1. Amino Acids with Aliphatic Side Chains 2. Amino Acids with OH groups 3. Amino Acids with SH groups 4. Amino Acids with Basic Groups 5. Amino Acids with Acidic Groups 6. Amino Acids with Aromatic Side Chains ALIPHATIC SIDE CHAINS (GAVIL) 1.Glycine Gly (G) 1H 2.Alanine Ala (A) 1C 3.Valine Val (V) 3C 4.Isoleucine Ile (I) 4C 5.Leucine Leu (L) 4C  OH GROUPS (STT) 1.Serine Ser (S) 1C, 1OH 2.Threonine Thr (T) 2C, 1OH 3.Tyrosine Tyr (Y) 1C, hexose,1OH  SH GROUPS (CM) 1.Cysteine Cys (C) 1C, 1SH 2.Methionine Met (M) 2C, 1SH, 1C  BASIC GROUPS (HAL) 1.Histidine His (H) 1C, 1 pentose 2.Arginine Arg (R) 3C, NCN c double bond 3.Lysine Lys (K) 4C, 1NH3+  ACIDIC GROUPS (AGAG) 1.Aspartic Acid Asp (D) 1C, 1COO- 2.Glutamic Acid Glu (E) 2C, 1COO- 3.Asparagine Asn (N) 2C, 1O, 1NH2+ 4.Glutamine Gln (Q) 3C, 1O, 1NH2  AROMATIC GROUPS (HPTT) 1.Histidine His (H) 1C, 1 pentose 2.Phenylalanine Phe (F) 1C, 1hexose 3.Tyrosine Tyr (Y) 1C, hexose, 1OH 4.Tryptophan Trp (W) 1C, 1hexose, 1pentose  IMINO GROUP (P) 1.Proline Pro(P) 1pentose, 1NH2, 1COO NONPOLAR SIDE CHAINS NONPOLAR SIDE CHAINS Net charge of zero at physiologic pH Neither acid or base Do not bind or give off protons Promote hydrophobic (water-fearing) interactions Cluster in the Interior of proteins Ex.: AVIL PTPT M  GLYCINE (GLY, G) Only amino acid with an achiral carbon (it has a hydrogen side chain) Used in the first step of heme synthesis: Glycine + Succinyl CoA  D-ALA Used in purine synthesis Major inhibitory neurotransmitter in the SPINAL CORD Alanine (Ala, A) Carries nitrogen from peripheral tissues to the liver Valine, Isoleucine and Leucine (VIL) Branched-chain amino acids whose metabolites accumulate in MSUD (Maple Syrup Urine Disease) Deficiency in branched chain α-ketoacid dehydrogenase Phenylalanine (Phe, F) Accumulate in phenylketonuria (deficiency in phenylalanine hydroxylase) Tryptophan Has the largest aromatic side chain Precursor for Niacin, Serotonin and Melatonin Methionine Transfer of methyl groups as SAM Precursor of Homocysteine Proline Not an amino, but an imino acid Contributes to fibrous structure of collagen and interrupts α-helices in globular proteins UNCHARGED, POLAR SIDE CHAINS UNCHARGED, POLAR SIDE CHAINS Uncharged: Net charge of zero at physiologic pH Polar: can form hydrogen bonds Cysteine Contains a sulfhydryl group that is an active part of many enzymes Two cysteines can be connected by a covalent Disulfide bond to form Cystine Keratin contains a lot of cystine (curly vs straight hair)  Tyrosine A precursor of Thyroxine and Melanin Serine Phosphorylation site of enzyme modification Often linked to carbohydrate groups in glycoproteins Serine and Threonine Sites for O-linked glycosylation in Golgi apparatus Asparagine Site for N-linked glycosylation in endoplasmic reticulum  Glutamine Deaminated by Glutaminase resulting in formation of ammonia ACIDIC SIDE CHAINS ACIDIC SIDE CHAINS Negatively-charged at physiologic pH because of the carboxylate group Since they are acids, they are Proton Donors Participate in ionic reactions GLUTAMATE The precursor of GABA and Glutathione BASIC SIDE CHAINS BASIC SIDE CHAINS Positively-charged at physiologic pH because of the amine group Since they are bases, they are Proton Acceptors At neutral pH: Arginine and Lysine will have a positive charge  HISTIDINE Precursor of Histamine Used in the diagnosis of Folic Acid Deficiency N-formiminoglutamate Excretion Rate: individuals deficient in folic acid excrete increased amount of FIGlu in urine particularly after ingestion of large doses of histidine ARGININE Precursor of Urea, Creatinine and Nitric Oxide  SELENOCYSTEINE, THE 21 ST AMINO ACID An L-α amino acid found in proteins e.g. peroxidases and reductases, selenoprotein P, iodothyronine deiodinases OPTICAL PROPERTIES OF AMINO ACIDS Except for Glycine all amino acids are Chiral L-configuration All amino acids in proteins D-configuration Bacterial walls, antibiotics Stereoisomers/Isomers/Enantiomers are exact mirror images of each other  CHARGE OF AMINO ACIDS Amino acids can have a positive, negative or zero charge depending on the pKa values and pH of the environment Zwitterion Molecule Chemical compound that has a total net charge of Zero Isoelectric pH or Isoelectric Point pH where the zwitterion predominates  AA is uncharged ESSENTIAL AMINO ACIDS PVT TIM HALL Phenylalanine, Valine, Tryptophan, Threonine, Isoleucine, Methionine, Histidine, Arginine, Leucine, Lysine Always ARGues, never TYRes CONDITIONALLY ESSENTIAL AMINO ACIDS 1. Arginine – may be made in the body, but usually not enough 2. Histidine – may be recycled, but should eventually be consumed since it is not made at all PROTEIN STRUCTURES LEVELS OF PROTEIN STRUCTURE 1. Primary Structure 2. Secondary Structure 3. Tertiary Structure 4. Quaternary Structure PRIMARY STRUCTURE Linear amino acid sequence of a protein Peptide Bonds attach an α-amino group of one AA to the α- carbonyl group of another very stable; can only be disrupted by hydrolysis or prolonged exposure to a strong acid/base at elevated temperatures PEPTIDE BONDS Peptide bonds in between two amino acids has a partial double bond character that makes the bond rigid and planar It is also generally in trans configuration SECONDARY STRUCTURE The folding of short (3-30) amino acid residues into geometrically ordered units Regular arrangements of AA that are located near each other in the linear sequence Stabilized by excessive hydrogen bonding 2 MAIN KINDS OF SECONDARY STRUCTURES 1. Alpha-helix 2. Beta-pleated sheets ALPHA HELIX Most common R-handed spiral with polypeptide backbone core side chains extend outward 3.6 AA per turn of spiral Disrupted by: Proline Large R groups (tryptophan) Charged R groups (acidic/basic AA) R groups are outside the helix and  BETA SHEET Surfaces appear flat and pleated 2 or more peptide chains parallel to each other Interchain and intrachain bonds  OTHER SECONDARY STRUCTURES Beta-bends Nonrepetitive (loop and coil) structures Motifs or Supersecondary Structures Combinations of adjacent secondary structures such as a βαβ unit, β barrel COMPARISON: ALPHA HELIX & BETA SHEET CHARACTERIST ALPHA HELIX BETA SHEET ICS General Shape R-handed spiral Sheets Direction of H Parallel to helix Perpendicular to bonds sheets Common Keratin (100% a Amyloid Examples helix) (Alzheimers) Hemoglobin Immunoglobulin (80% a helix) s  TERTIARY STRUCTURES Overall three-dimensional shape of the protein Ex.: Globular proteins, Fibrous proteins Refers to the folding of Domains and their final arrangement in the polypeptide Stabilized by: Disulfide bonds Hydrophobic interactions Hydrogen bonds DOMAINS Fundamental functional and three-dimensional structural units of a polypeptide Formed by a combination of motifs  QUATERNARY STRUCTURES Structure of proteins consisting of more than 1 polypeptide chain Held together by noncovalent bonds  DENATURATION Disruption of a protein’s structure When protein becomes unfolded and disorganized, they become dysfunctional May be reversible Causes of denaturation: 1. Heat 2. Organic Solvents 6. Ions of heavy metals like lead & mercury 3. Mechanical Mixing DENATURAT ION CLINICAL CORRELATIONS 1. Prion Diseases 2. Alzheimer’s Disease REFERENCES 1. http:// www.biology.arizona.edu/biochemistry/problem_sets/aa/aa.html 2. Harpers Biochemistry, 30th Edition