Amino Acids, Peptides

Amino Acids Amino acids are the building blocks of proteins. contain a carboxylic acid group and an amino group on the alpha () carbon. are ionized in solution. each contain a different side group (R).

Amino acids are derivatives of carboxylic acids formed by substitution of -hydrogen for amino functional group. Composed of C, H, O, N usually S, P Always has a NH2

All the standard amino acids except (glycine) the α carbon is asymmetric. α carbon is bonded to four different substituent groups: carboxyl group amino group R group hydrogen atom.

All amino acids start with this structure The “R” stands for “anything”

Classification of Amino Acids

CLASSIFICATION: Classified based on the properties of their R groups. Tendency to interact with water at biological pH (near pH 7.0).

those whose R groups are: nonpolar and aliphatic 2)aromatic (generally nonpolar) 3) polar but uncharged 4) negatively charged 5) positively charged. Within each class, there are gradations of polarity, size, and shape of the R groups.

nonpolar (hydrophobic) with hydrocarbon side chains. polar (hydrophilic) with polar or ionic side chains. acidic (hydrophilic) with acidic side chains. basic (hydrophilic) with –NH2 side chains. Nonpolar Polar Acidic Basic

Nonpolar Polar Acidic Basic

1) Nonpolar Aliphatic R group: The hydrocarbon R groups are nonpolar and hydrophobic. The bulky side chains of alanine, valine, leucine, and isoleucine, promote hydrophobic interactions within protein structures.

Nonpolar Amino Acids An amino acid is nonpolar when the R group is H, alkyl, or aromatic.

Amino acids can be classified by R groups

2) Polar, Uncharged R Groups : Are more soluble in water than nonpolar amino acids, because they contain functional groups that form hydrogen bonds with water. Includes: Serine(OH) Threonine(OH) Cysteine( S) Methionine(S, sulphur atom) Asparagine(NH2, amide group) Glutamine. (NH2)

Polar Amino Acids An amino acid is polar when the R group is an alcohol, thiol, or amide.

Tryptophan and tyrosine, and phenylalanine absorb ultraviolet light. 3) Aromatic R Groups: Phenylalanine (Phe), Tyrosine (tyr), and Tryptophan (Trp), are relatively nonpolar. The OH group of tyrosine can form hydrogen bonds, hence important functional group in the activity of some enzymes. Tyrosine and tryptophan are more polar than phenylalanine because of the tyrosine hydroxyl group and the nitrogen of the tryptophan indole ring. Tryptophan and tyrosine, and phenylalanine absorb ultraviolet light.

indole ring

4) Negatively Charged (Acidic) R Groups: Include: 1) Aspartate 2) Glutamate Each have a second carboxyl group. These are the parent compounds of asparagine and glutamine.

5) Positively Charged (Basic) R Groups: Includes: lysine, has a second amino group at the e position on its aliphatic chain; Arginine, which has a positively charged guanidino group; Histidine, has an imidazole group.

imidazole guanidino

Acidic and Basic Amino Acids An amino acid is acidic when the R group is a carboxylic acid. basic when the R group is an amine.

Essential Amino Acids Clue to remember: PVT TIM HALL Proteinaceous AA − proteins consist of 20 AA. Essential − organism is not able to synthesize these AA but accept from food. Nonessential − organism produced from essential AA by transamination. Methionine Histidine Arginine Lysine Leucine Phenylalanine Valine Threonine Tryptophan Isoleucine

Description – general properties

GENERAL PROPERTIES OF AMINO ACIDS: Isomerism: Two types: 1) L form 2) D forms. stereo-isomerism: all amino acids except glycine exist as D and L- isomers. In D-amino acids, -NH2 group (right). In animals and plants. In L-amino acids (left) ,occur in bacteria.

Amino Acids Steric relationship of the stereoisomers of Alanine to the absolute configuration of L- and D-glyceraldehyde The amino acid residues in proteins are the L isomers

AA are optically active molecules and asymmetry of their mirror images is not superimposable (except in the case of glycine where the R-group is hydrogen) according new UIPAC nomenclature L- D- forms were replaced for (S)- and (R)- system

2) Ionization: Amino acids in aqueous solution are ionized and can act as acids or bases. Those having a single amino group and a single carboxyl group crystallize from neutral aqueous solutions as fully ionized species known as zwitterions (German for "hybrid ions"), each having both a positive and a negative charge.

Zwitterionic structure is neutral and its value of pH is called isoelectric point.

Amino Acids Can Act as Acids and as Bases. 3) Amphoteric nature: Amino Acids Can Act as Acids and as Bases. When a crystalline amino acid, such as alanine, is dissolved in water, it exists in solution as the dipolar ion, or zwitterion, which can act either as an acid (proton donor), or as a base (proton acceptor)

majority of amino acids has amphoteric character – functional group –COOH is the reason of acidity and –NH2 group causes basic properties. in basic environment AA dissociate proton to form carboxyl anion –COO-. Basic surround defends –NH2 against dissociation.

in basic environment AA dissociate proton to form carboxyl anion –COO- in basic environment AA dissociate proton to form carboxyl anion –COO-. Basic surround defends –NH2 against dissociation. in acidic environment AA accept proton to form amonium cation –NH3+. Acidic environment defends –COOH against dissociation.

Physical propeties – AA are colourless crystalline substances soluble in water and insoluble in organic solvents with high melting point. Arginine Valine Alanine Lysine

Reactions of amino acids

Polymerization – form peptides, proteins and enzymes A condensation reaction between the carboxyl of one amino acid and the amino group of another forms a peptide bond. Peptides Oligopeptides − condensation of 2 – 10 AA units Polypeptides − condensation of 11 – 100 AA units Proteins − more than 100 AA units

Disulfide linkage – conversion of cysteine to cystine is like a conversion of thiols to disulfides by mild oxidizing agents. This conversion can be reversed by mild reducing agents. Disulfide bonds stabilize protein structure by providing cross-link.

e.g. two polypeptide chains of insuline Reversible formation of disulfide bond by the oxidation of two molecules of cysteine e.g. two polypeptide chains of insuline

Peptides

The Peptide Bond Amino acids can be linked together by covalent bonds The bonds are formed between the -carboxyl group of one amino acid and the -amino group of the next one Water is removed in the process and the linked amino residues remain attached to one another

This bond is called a peptide bond and peptides are formed When hundreds of amino acids are joined in this process, a polypeptide is formed The compound formed may also be referred to as an amide The bond formed between the carbon and nitrogen is a single bond

The Peptide Bond Pentapeptide hydrolysis condensation Serylglyciltyrosylalanylleucine or Ser-Gly-Tyr-Ala-Leu SGYAL Two amino acid molecules can be covalently joined through a substituted amide linkage, termed a peptide bond, to yield a dipeptide Peptides are named beginning with the amino-terminal residue, which by convention is placed at the left. just a few residues  oligopeptide many residues  polypeptide

Some Small Peptides of Physiological Interest Simplest combination of amino acids are dipeptides in which two amino acids are linked together An example is the dipeptide carnosine which is found in muscle tissue The compound is also known as -alanyl-L-histidine The peptide bond is formed between the carboxyl group of the -alanine and the amino group of histidine Aspartame is another dipeptide which has health implications Glutathione a tripeptide is a scavenger for oxidizing agents

Glutathione is -glutamyl-L-cystenylglycine Two pentapeptides found in the brain are enkaphalins which are natural analgesics Tyr-Gly-Gly-Phe-Leu (leucine enkaphalin) Tyr-Gly-Gly-Phe-Met (Methionine enkaphalin) Opiates bind to the same receptors in the brain intended for the enkaphalins and hence produce their physiological activities Oxytocin and vasopressin have cyclic structures Each has 9 amino acid residues and an amide group at the C-terminal and disulfide bonds at positions 1 and 6

There are several levels of protein structure Multisubunit proteins Arrangement is space of polypeptide subunits Particularly stable arrangements of amino acid residues giving rise to recurring structural paterns All aspects of the 3-D folding of a polypeptide Includes disulfide bonds

~ 300 additional amino acids have been found in cells Uncommon amino acids also have important functions 1 2 3 4 5 a b g plant cell wall, collagen myosin prothrombim, a # of Ca+ binding proteins elastin Lysine residues Residues created by modification of common residues already incorporated into a polypeptide rare, introduced during protein synthesis rather than created through a postsynthetic modification ~ 300 additional amino acids have been found in cells

Reversible amino acid modifications involved in regulation of protein activity

Examples of Clinical Aminoacidurias Metabolic defects: Phenylketonuria (Phe), Tyrosinemias (Phe,Tyr), Maple Syrup Urine Disease (Leu, Val, Ile), Alcaptonuria (Tyr) Absorption/transport defects: cystinuria (Cys), Hartnup disease , Fanconi’s Syndrome These diseases are generally diagnosed from indicators in the urine or plasma.