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Amino Acids and Peptides. Dr. Henry O. Ogedegbe Department of EHMCS . Amino Acids-Formula and Three Dimensional Structure. Proteins are polypeptides of amino acids linked together by peptide bonds
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Amino Acids and Peptides Dr. Henry O. Ogedegbe Department of EHMCS
Amino Acids-Formula and Three Dimensional Structure • Proteins are polypeptides of amino acids linked together by peptide bonds • The positively charged nitrogen containing amino group is on one side and negatively charged carboxyl group is at the other end • Along the chain is a series of different side chains that are different for each of the amino acids • A linkage of two amino acids is a dipeptide while the linkage of three amino acids is a tripeptide • For a chain 20 amino acids long there are more than a billion possible sequences
Amino Acids-Formula and Three Dimensional Structure • Only 20 amino acids are found in proteins • The general structure involve an amino group and a carboxyl group both bonded to the -carbon • The -carbon is also bonded to a hydrogen and a side chain group represented by the letter R • The R group gives identity to the particular amino acid • An important property of the amino acids are their stereochemistry or three dimensional shape • The -carbons in all amino acids except glycine have four different groups bonded to them
Amino Acids-Formula and Three Dimensional Structure • This gives rise to two nonsuperimposable mirror image forms or chiral forms • Glycine has two hydrogen atoms bonded to the -carbon • These nonsuperimposable mirror image forms are referred to as stereoisomers • The two stereoisomers of amino acids are classified into L or D forms from the latin laevus and dexter • Glyceraldehyde is the standard molecule from which other chiral compounds are compared • In the L form of glyceraldehyde the hydroxyl group is on the left side of the molecule
Amino Acids-Formula and Three Dimensional Structure • In the D form the hydroxyl group is on the right side of the molecule • In an amino acid, the position of the amino group on the left or right side of the -carbon determines the L or D designation • The amino acids in proteins are the L forms • Most D amino acids in nature occur in bacterial cell walls and in some antibiotics but they are not found in protein
The Structure and Properties of the Individual Amino Acids • The classification of the amino acids are based on several criteria including • Polar or non polar • Presence of an acidic or basic group in the side chain • Presence of functional groups in the side chains • Nature of those groups • In the case of glycine two hydrogen atoms are bonded to the -carbon • In all other amino acids the the side chain is larger and more complex
The Structure and Properties of the Individual Amino Acids • Side chain carbon atoms are designated with Greek alphabets counting from the -carbon • The carbon atoms are in turn , , , and and the terminal carbon atom is referred to as -carbon • Amino acids may be referred to by the three or one letter abbreviation of their names • Group 1 Amino Acids with Nonpolar Side Chains: • This group consist of alanine, valine, leucine, isoleucine, proline, phenylalanine, tryptophan, and methionine • Glycine may be added to this group because it lacks a polar side chain
The Structure and Properties of the Individual Amino Acids • Members of the group including alanine, valine, leucine, and isoleucine have aliphatic hydrcarbon side chains • Proline has an aliphatic cyclic structure and the nitrogen is bonded to two carbon atoms • The amino acid of proline is a secondary amine unlike all other common amino acids which are primary amines • The hydrocarbon group in phenylalanine is aromatic • The side chain in tryptophan contains an indole-ring which is aromatic
The Structure and Properties of the Individual Amino Acids • Group 2 Amino Acids with Electrically Neutral Polar Side Chains: • This group of amino acids have polar side chains that are electrically neutral at neutral pH • The group includes serine, threonine, tyrosine, cysteine, glutamine, and asparagine. • Glycine may also be included in this group because it lacks a nonpolar side chain • In threonine and serine, the polar group is a hydroxyl (OH) bonded to an the aliphatic hydrocarbon groups
The Structure and Properties of the Individual Amino Acids • In tyrosine, the hydroxyl group in bonded to an aromatic hydrocarbon group which is a phenol • It is a stronger acid than an aliphatic alcohol • Side chain of tyrosine can lose a proton whereas those of serine and threonine do not • The polar side chain in cysteine consist of an –SH (thio) group • They reacts with other cysteine molecule to form disulfide (– S – S –) bridges in proteins and in an oxidative reaction • The thio group can lose a proton
The Structure and Properties of the Individual Amino Acids • Asparagine and glutamine have amide groups which are derived from carboxyl groups in the side chains • Asparagine and glutamine may be considered as derivatives of the group 3 amino acids glutamic acid and aspartic acid • Group 3 Amino Acids with Carboxyl Groups in Their Side Chains: • Aspartic acid and glutamic acids have carboxyl groups in their side chains in addition to the one present in all amino acids • A carboxyl group can lose a proton and form the corresponding carboxylate anion glutamate and aspartate
The Structure and Properties of the Individual Amino Acids • As a result of presence of the carboxylate, the side chains are negatively charged at neutral pH • The side chain carbonyls form side chain amide groups with – NH2 to yield glutamine and asparagine • The side chains amide groups are electrically neutral at neutral pH like the other group 2 amino acids • Group 4 Amino Acids with Basic Side Chains: • Histidine, lysine and arginine have basic side chains • In lysine and arginine side chains are positively charged at neutral pH
The Structure and Properties of the Individual Amino Acids • The pKa of histidine side chain, imidazole group is 6.0 which is close to physiological pH • Properties of many proteins depend on whether or not individual histidine residues are charged • Histidine facilitates enzyme reactions by serving as a proton donor/acceptor • The side chain amino group in lysine is attached to an aliphatic hydrocarbon tail • In arginine the side chain basic group the guanidino group is complex in structure and bonded to an aliphatic hydrocarbon tail
The Structure and Properties of the Individual Amino Acids • Uncommon Amino Acids: • The uncommon amino acids are derived from common amino acids • They are produced by modification of parent amino acid after protein synthesis by the organism • This is a process known as post translational modification • Hydroxyproline and hydroxylysine are examples • They differ from the parent in having hydroxyl groups on their side chains • They are found in few connective tissue proteins such as collagen
The Structure and Properties of the Individual Amino Acids • Thyroxine is different from tyrosine in having an extra iodine containing aromatic group on the side chain • It is found only in the thyroid gland
Titration Curve of The Amino Acids • Carboxyl group and amino group of free amino acids are charged at neutral pH • The carboxylate portion is negatively charged and the amino group positively charged • Amino acids without charged groups on their side chains exist in neutral solutions as zwitterions with no net charge • A zwitterion has equal positive and negative charges in solution • It is electrically neutral • Titration curve of an amino acid indicates the reaction of each functional group with hydrogen ions
Titration Curve of The Amino Acids • In alanine, the carboxyl and amino groups are the two titratable groups • At very low pH alanine has a protonated carboxyl group and a positively charged protonated amino group • Thus alanine has under such conditions a net positive charge of 1 • When base is added, the carboxyl group loses its proton and it becomes negatively charged carboxylate group • At this point, alanine now has no net charge • As more base is added, the protonated amino group loses its proton and alanine now has a negative charge of 1
Titration Curve of The Amino Acids • The titration curve of alanine is that of a diprotic acid
Titration Curve of The Amino Acids • In histidine, the imidazole side chain contributes a titratable group • At low pH the the histidine has a net positive charge of 2 • Both amino group and imidazole have positive charges • As base is added the the carboxyl group loses a proton and becomes a carboxylate • The histidine now has a positive charge of 1 • As more base is added, the charged imidazole loses its proton and the histidine has no net charge • At higher pH the amino group loses its proton and the histidine now has a net negative charge of -1 • The titration curve of histidine is that of a triprotic acid
Titration Curve of The Amino Acids • The amino acids have characteristic Kas and pKas of their titratable groups • The pKas of -carboxyl groups are low at around 2 while the pKas of amino acid groups range from 9 to 10.5 • The pKas of side chains depend on the groups chemical nature • Classification of an amino acid as an acid or a base depends of the pKa of the side chain • The side groups are still titratable after incorporation of the amino acid in a protein • The pKa of the titratable group on the side chain may not be the same as in a free amino acid
Titration Curve of The Amino Acids • Amino acids, peptides and proteins can have different charges at a given pH • Alanine and histidine both have net charges of -1 at high pH above 10 • The carboxylate is the charged anion • At lower pH around 5 alanine is a zwitterion with no net charge but histidine has a net charge of +1 at pH 5 • The imidazole group is protonated. • This is the basis of electrophoresis a method for separating molecules based on their charges • The pH at which a molecule has no net charge is called the isoelectric point
Titration Curve of The Amino Acids • At its PI a molecule stops migrating in an electric field • The PI of amino acid may be determined by the following equation • PI = I/2 (pKa1 + pKa2)____ __
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 • One pair of electrons is shared between the two atoms • With a shift in the position of the electrons, the bond can be written as a double bond • This shifting of electrons results in resonance structure • These are structures that differ in the position of the electrons • The positions of double and single bond in one resonance structure are different from their position in another resonance structure of the same compound • Thus the peptide bond can be written as a hybrid of two structures, one with a single bond between carbon and nitrogen and the other with a double bond
The Peptide Bond • The resonance structures of the peptide bond lead to a planar amide group
The Peptide Bond • The peptide bond has partial double bond characteristic Therefore the peptide group that forms link between the two amino acids in planar • As a result of the resonance stabilization, the peptide bond is stronger than an ordinary single bond • There is free rotation around the bonds between the -carbon of a given amino acid residue and the amino nitrogen and carbonyl carbon of that residue • However there is no significant rotation around the peptide bond • This stereochemistry is important in determining how the protein backbone folds
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
The Peptide Bond • 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
The Peptide Bond • Peptide bonds form the cyclic structure in some peptides • Gramicidin S and tyrocidine A are antibiotic that contain D amino acids as well as L amino acids • They both also contain the amino acid ornithine which does not occur in proteins but plays a role in metabolic intermediate several common pathways
References • 1. Biochemistry, Campbell/Farrel 3rd Edition • 2. Fundamentals of Biochemistry, Voet D, Voet JG, Pratt CW • 3. Biochemistry, Mathews/van Holde 2nd Edition