Chapter 3: Amino Acids

& Peptides
Dr. Bacolod, Chuckie Miguel A.
Silliman University Medical School
BIOMEDICAL IMPORTANCE

• Amino acids provide monomer units of the long PP

chains of proteins
• NES= hormones, hormone-releasing fx,
neuromodulators, and NTs
BIOMEDICAL IMPORTANCE

• Essential AA= type of AA which cannot be synthesized

by humans and other higher animals (10 of the L -α-
amino acids present in proteins)

• kidneys filter over 50g/d of free AA from the arterial

renal blood.
• only traces seen in urine
BIOMEDICAL IMPORTANCE

• Certain microorganisms secrete free D -amino acids, or

peptides that may contain both D - and L -α-amino acids
• bacterial peptides of therapeutic value (bacitracin,
gramicidin A, bleomycin).
• Other microbial peptides are toxic= microcystin and
nodularin are lethal in large doses; small quantities
form hepatic tumors
The Genetic Code Specifies 20 L -α-
Amino Acids
• Proteins= synthesized from 20 AA encoded by
nucleotide triplets (codons)
• peptides and protein sequence represented as 1 and 3
letter abbreviations for each AA
• R groups can be characterized as hydrophilic or
hydrophobic
• Other AA come from posttranslational modification (ex.:
hydroxyproline in collagen)
Selenocysteine, the 21st Protein L -
α-Amino Acid
• Selenocysteine is present in proteins from every domain
of life.
• Humans ~two dozen selenoproteins: include certain
peroxidases and reductases, selenoprotein P,
iodothyronine deiodinases
• commonly termed the “21st amino acid.”
Stereochemistry of the Protein
Amino Acids
• All of the 20 amino acids are of the L-configuration
except glycine
• in mammals the biochemical reactions of L -α- amino
acids, their precursors, and their catabolites are
catalyzed by enzymes that act exclusively on L -isomers
Posttranslational Modifications
Confer Additional Properties
• a set of just 21 L -α-amino acids clearly suffices for the
formation of most proteins however, posttranslational
modifications can generate novel R groups that impart
further properties
• Ex.: formation of collagen, formation of proteins in
coagulation cascade
L -α-Amino Acids Serve Additional
Metabolic Roles
AA as building blocks:
• tyrosine=>thyroid hormone
• tyrosine & phenylalanine=>epinephrine, NE, & DOPA
• Glutamate=>GABA
• Ornithine & citrulline: intermediates in urea biosynthesis
• homocysteine, homoserine, & glutamate-γ-
semialdehyde: intermediates in the metabolism of the
protein amino acids.
Certain Plant L -α-Amino Acids Can
Adversely Impact Human Health

neurolathyrism
• neurologic disorder characterized by progressive &
irreversible spastic paralysis of the legs
• caused by seeds and seed products of three species of
the legume Lathyrus
Certain Plant L -α-Amino Acids Can
Adversely Impact Human Health
Cycad seeds
• from consumption of either fruit bats that feed on cycad
fruit, or flour made from cycad seeds.
• risk factor for ALS–Parkinson dementia complex in
Guam
Certain Plant L -α-Amino Acids Can
Adversely Impact Human Health
D -Amino Acids

D -Amino acids that occur naturally:

• free D -serine & D -aspartate (human brain tissue)
• D -alanine and D -glutamate (cell walls of gram +
bacteria)
• D -amino acids in certain peptides and antibiotics
produced by bacteria, fungi, reptiles, and amphibians.
Take note..

• Both D -amino acids and non–α-amino acids occur in

nature, but proteins are synthesized using only L -α-
amino acids.
• D -Amino acids do, however, serve metabolic roles, not
only in bacteria, but also in humans.
PROPERTIES OF THE
FUNCTIONAL GROUPS
OF AMINO ACIDS
Amino Acids May Have Positive,
Negative, or Zero Net Charge
• at physiologic pH (pH 7.4), carboxyl groups exist almost
entirely as R—COO - and amino groups predominantly
as R—NH 3+
• a-amino group is protonated (pKa ∼ 9) and carries a
positive charge , and the carboxyl group is
dissociated (pKa ∼ 2) and carries a negative charge .
Amino Acids May Have Positive,
Negative, or Zero Net Charge
• Positive charge: histidine (imidazole group) and
arginine (guanidino group); distributed between two
nitrogens (histidine) or three nitrogens (arginine)
• zwitterions: Molecules that contain an equal number of
positively and negatively charged groups that bear no
net charge
pKa Values Express the Strengths of
Weak Acids
• strengths of weak acids are expressed as their pKa
• The net charge on an amino acid depends on the pKa
values of its functional groups and the pH of the
surrounding medium.
At Its Isoelectric pH (pI), an Amino
Acid Bears No Net Charge
• Zwitterions are one example of an isoelectric species
• The isoelectric pH (pI) is the pH midway between pKa
values for the ionizations on either side of the isoelectric
species.
• knowledge of the pI guides selection of conditions for
electrophoretic separations.
pKa Values Vary With the
Environment
• nonpolar environment= raises the pKa of carboxyl
group making it a weaker acid, but lowers the pKa of an
amino group, making it a stronger acid
• presence of charged groups can either stabilize or
destabilize a developing charge
• Therefore, the pKa values of the R groups of free amino
acids in aqueous solution provide only an approximate
guide to their pKa values when present in proteins.
The Solubility of Amino Acids
Reflects Their Ionic Character
• AA charges ensure that they are readily solvated in
polar solvents but insoluble in non polar solvents
• Amino acids do not absorb visible light
• except, tyrosine, phenylalanine, & tryptophan
THE α-R GROUPS DETERMINE THE
PROPERTIES OF AMINO ACIDS
• carboxylic acid groups: include formation of esters,
amides, and acid anhydrides
• amino groups: acylation, amidation, and esterification
• hydroxilic and sulfuric groups: oxidation and
esterification
THE α-R GROUPS DETERMINE THE
PROPERTIES OF AMINO ACIDS
• glycine= the smallest amino acid, can be
accommodated in places inaccessible to other amino
acids
• The charged R groups of basic & acidic amino acids
stabilize specific protein conformations via ionic
interactions, or salt bridges.
THE α-R GROUPS DETERMINE THE
PROPERTIES OF AMINO ACIDS
• Histidine: (in enzymatic catalysis) the pKa of its
imidazole proton permits histidine to function at
neutral pH as either a base or an acid catalyst
without the need for any environmentally induced
shift.
• serine and cysteine: can function as excellent
nucleophiles during enzymatic catalysis
• The —OH groups of serine, tyrosine, and threonine:
serve as points of covalent attachment for phosphoryl
groups that regulate protein function
Take Note..

• The R groups of amino acids determine their unique

biochemical functions.
• Amino acids are classified as basic, acidic, aromatic,
aliphatic, or sulfur-containing based on the composition
and properties of their R groups.
Amino Acid Sequence Determines
Primary Structure
• Amino acids are linked together by peptide bonds.
• primary structure: number and order of the amino acid
residues in a polypeptide
• aminoacyl residues: Amino acids present in peptides;
• referred to by replacing the ate or ine suffixes with yl
The Peptide Bond Has Partial
Double-Bond Character
• Peptide structures are written as if a single bond linked
the α-carboxyl and α-nitrogen atoms but this is actually
a partial double-bond character
• The partial double-bond character render the four
atoms of the peptide bond coplanar, and hence
restrict the number of possible peptide
conformations.
Noncovalent Forces Constrain
Peptide Conformations
• Folding of a peptide probably occurs coincident with its
biosynthesis
• reflects the collective contributions of the amino acid
sequence, noncovalent interactions, and the
minimization of steric hindrance between residues.
Peptides Are Polyelectrolytes

• The peptide bond is uncharged at any pH of physiologic

interest.
• Formation of peptides from amino acids is therefore
accompanied by a net loss of one positive and one
negative charge per peptide bond formed.
• In amino acids, the net charge on a peptide depends on
the pH of its environment and on the pKa values of its
dissociating groups.
• End
• 10 item quiz next meeting