AMINO ACIDS & PEPTIDES

BIOMEDICAL IMPORTANCE
Hydrophilic Hydrophobic
L-a-amino acids Arginine Alanine
• provides the monomer units where the long Asparagine Isoleucine
peptide of proteins are synthesized Aspartic Acid Leucine
• participates in cell functions as diverse as Cysteine Methionine
nerve transmission and the biosynthesis of Glutamic Acid Phenylalanine
porphyrins, purines, pyrimidines and urea. Glutamine Proline
Glycine Typtophan
Neuroendocrine system Histidine Tyrosine
• employs short polymers of AA Lysine Valine
called peptides Serine
• used as hormones, hormone releasing Threonine
factors, neurotransmoudulators and
neruotransmitters SELENOCYSTEINE, THE 21ST AA

• Humans cannot synthesize 10 of the L-a-AA • an L-a-AA found in proteins from

present in proteins in amounts adequate to
support infant growth and maitain adult
health.
• Human diet must contain adequate
quantities of nutritionally essential
AA
• 50g of AA are filtered by the kidney
from renal blood
• Only traces of free AA normally appear
in urine because AA are almost totally
absorbed in PCT, conversing them for
protein synthesis and other functions.
Lathyrism
• ingestion of AA present in the seeds
of legumes of the genus Lathyrus
• irreversible disease in which individuals lose
control of their limbs
every domain of life
• commonly termed as the 21st A
• selenium replaces sulfur of its elemental
analog cysteine
• not a product of a posttranslational
modification -> inserted directly into a
growing peptide during translation
• incorporation is specified by tRNA-SEC
which utilizes the UGA anti-codon that
normally signals stops.
• protein synthetic apparatus can identify a
selenocysteine-specific UGA codon by the
presence of an accompanying stem-loop
structure — the selonocysteine insertion
element — found in the untranslated region
of mRNA
STEREOCHEMISTRY

GENETIC CODES SPECIFIES 20 AA • a-carbon of every AA is chiral except glycine

Codons
• nucleotide triplets that code AA
• can potentially code more than 20 AA,
the genetic is redundant since several
amino acids are specified by multiple
codons.
• can be classified as hydrophilic or
hydrophobic
• some proteins contain additional amino acids
that arise by the post-translational
modification of an amino acid already in a
peptide
• modifications significantly extend the biologic
diversity of proteins by altering their
solubility, stability, catalytic activity and
interaction with other proteins
Posttranslational changes
• can generate novel R-groups that impart
• all AA follow the configuration of
L- glyceraldehyde
• almost all proteins are (R)
• failure to use (R) or (S) to express absolute
stereochemistry is no mere historical
aberration
• In mammals — biochem reactions of L-a-AA,
their precursors and their catabolites are
catalyzed by enzymes that act exclusively on
L-isomers, respective of their absolute
configuration.
POSTTRANSLATIONAL MODIFICATIONS
Prokaryotes — > Pyrrolysine —> Proteins
Plants — > azetidine-2-carboxylic acid —>
Protein
further properties
AMINO ACIDS & PEPTIDES
• amino side chains of histones are subject to
numerous modifications, including
acetylation and methylation of lysine and
methylation and deamination of arginine
L-A-AA SERVE ADDITIONAL ROLES
• Tyrosine —> thyroid hormones
• Glutamate —> neurotransmitter —> y-
amunobutyric acid (GABA)
• Ornithine and Citrulline —> intermediates in
urea biosynthesis
• Homocysteine, Homoserine and Glutamate-
y-semialdehyde —> intermediary
metabolism of protein AA
• Phenyalanine and Tyrosine —> Epi,
Norepi and dihydroxyphenylalanine
(DOPA)
PLANT L-A-AA IMPACTS HEALTH
Neuroalythrism
• Legume Lathyrus
• neurological disorder; progressive and
irreversible spastic of the legs
• occurs widely during famine
• legumes contain osteoalthyrogen y-glutamyl-
B-aminopropionitrile
Cycad seeds
• risk factor
• amyotrophic lateral sclerosis-Parkinson
dementia complex
AMINO ACIDS MAY BE + OR —
R—COOH — R—COO- + H+ R—
NH3+ — R—NH2 + H+
• charged and uncharged forms of the
ionizable weak acid groups —COOH and —
NH3+ exist in dynamic protonic equilibrium
At physiologic pH
• carboxyl groups exist almost entirely
as R—COO-
• amino groups predominantly as R—NH3+
Zwitterions
• molecules that contain an equal number of
positively and negatively charged groups
• no net charge
• AA do not absorb visible light —> colorless
• except tyrosine, phenylalanine and
• any pH sufficiently high for an uncharged
amino group to predominate, a carboxyl
group will be present as R—COO-
PKA EXPRESSES THE STRENGTH
pKa
• expresses strength of weak acids
• net charge on an amino acid depends upon
the pKa values of its functional groups and
the pH of the surrounding medium
ISOELECTRIC PH
pI
• isoelectric pH
• pH midway between pKa values for the
ionizations on either side of the isoelectric
species
Polyprotic Acids
• pI is also the pH midway between pKa
values on either side of the isoionic species.
• apply to all polyprotic acids regardless of the
number of dissociable goups present
PKA VARIES WITH ENVIRONMENT
Nonpolar environment
• less capacity than water for stabilizing
charged species
• carboxyl group —> ↑pKa —> weak acid
• amino group —> ↓ pKa —> stronger acid
Adjacent oppositely charged group —>
stabilize
Adjacent similary charged group —>
destabilize
• pKa values of the R groups of AA in aq
soln provide only an approximate guide to
their pKa values when present in proteins.
pKa of side chain
• depends on its location within a protein
• 3 pH units —> AA at active enzyme
sites SOLUBILITY OF AMINO ACIDS
• charges conferred by the dissociable
functional groups of AA ensure that they
are readily solvated by polar solvent like
H2O and ethanol but insoluble in nonpolar
solvents like benzene, hexane or ether
tryptophan —> UV (250-290nm)
• tryptophan —> best at 280nm
AMINO ACIDS & PEPTIDES
• bond that connects a carbonyl to an a-
R GROUPS DETERMINE PROPERTIES nitrogen cannot rotate —> would break the
partial double bond
Carboxy group • C,H,O and N peptide bond are coplanar
• formation of esters, amides and acid
anhydrides PEPTIDES ARE POLYELECTROLYTES

Amino group Peptide bonds

• acylation • uncharged at any pH of physiologic interest
• amidation
• esterification • peptide formation from AA —> net loss of
1 positive and 1 negative per peptide bond
—OH and —SH groups formed
• oxidation and esterification • peptides are charged at physiologic pH

Glycine
• smallest amino acid
• occurs where peptides bend sharply

• the hydrophobic R groups of alanine, valine,

leucine and isoleucine and the aromatic R
group of phenylalanine, tyrosine and
tryptophan —> in cystosolic proteins

Charged R group
• stabilizes specific protein conformations via
ionic interactions or salt bridges

• the primary alcohol group of serine and the

primary thioalcohol group of cysteine are
excellent nucleophiles

• —OH groups of serine, tyrosine and

threonine —> points of covalent attachment
for phosphoryl groups —> regulate protein
function

AA SEQUENCE DETERMINES STRUCTURE

Aminoacyl residues
• AA in peptides

Peptides
• named as derivatives of the carboxyl
terminal aminoacyl residue

PEPTIDE BOND HAS DOUBLE BOND

• a-carboxyl and a-nitrogen atoms exhibits

partial double bond character