Download Biosynthesis of the nutritionally nonessential amino acids

BIOSYNTHESIS OF THE
NUTRITIONALLY
NONESSENTIAL AMINO
ACIDS
BIOSYNTHESIS OF THE NUTRITIONALLY
NONESSENTIAL AMINO ACIDS
• AMINO ACID DEFICIENCY STATES CAN RESULT IF NUTRITIONALLY ESSENTIAL
AMINO ACIDS ARE ABSENT FROM THE DIET, OR ARE PRESENT IN INADEQUATE
AMOUNTS.
• AMINO ACID DEFICIENCY STATES, WHILE COMPARATIVELY RARE IN THE WESTERN
WORLD, ARE ENDEMIC IN CERTAIN REGIONS OF WEST AFRICA WHERE DIETS RELY
HEAVILY ON GRAINS THAT ARE POOR SOURCES OF TRYPTOPHAN AND LYSINE.
These nutritional disorders include:
• kwashiorkor, which results when a child is weaned onto a
starchy diet poor in protein.
• marasmus, in which both caloric intake and specific amino
acids are deficient.
• Patients with short bowel syndrome unable to absorb
sufficient quantities of calories and nutrients suffer from
significant nutritional and metabolic abnormalities.
• a dietary deficiency of vitamin C is associated with an
impaired ability of connective tissue to form hydroxyproline
and hydroxylysine. The resulting conformational instability
of collagen results in bleeding gums, swelling joints, poor
wound healing, and ultimately in death.
• Menkes' syndrome, characterized by kinky hair and growth
retardation, results from a dietary deficiency of copper,
which is an essential cofactor for lysyl oxidase.
• Ehlers-Danlos syndrome, a group of connective tissue
disorders that result in mobile joints and skin abnormalities
due to defects in the genes that encode enzymes lysyl
hydroxylase.
• Nutritionally essential & nutritionally non
essential amino acids
The terms "essential" and "nonessential" are
misleading since all 20 common amino acids are
essential to ensure health.
Glutamate Dehydrogenase, Glutamine Synthetase, Amino
transferases Play Central Roles in Amino Acid Biosynthesis
A. Synthesis from α-keto acids
Alanine, aspartate, and
Glutamate are synthesized by
transfer of an amino group to the
α-keto acids pyruvate,
oxaloacetate, and α-ketoglutarate, respectively.
Glutamate is unusual in that it
can also be synthesized by
reductive amidation of αketoglutarate catalyzed by
glutamate dehydrogenase
B. Synthesis by amidation
1. Glutamine: This amino acid, which
contains an amide linkage with
ammonia at the γ-carboxyl, is formed
from glutamate by glutamine synthetase
The reaction is driven by the hydrolysis
of ATP.
This reaction also serves as a major
mechanism for the detoxification of
ammonia in brain and liver .
2. Asparagine: This amino acid, which
contains an amide linkage with
ammonia at the β-carboxyl, is formed
from aspartate by asparagine
synthetase, using glutamine as the
amide donor rather than ammonium
ion. The reaction requires ATP.
C. Proline
Glutamate is converted to proline by cyclization and
reduction reactions.
Biosynthesis of proline similar to those of proline catabolism,
but in which glutamate -phosphate is an intermediate.
D. Glycine, Serine, and Cysteine
Glycine: Glycine aminotransferases can catalyze the synthesis
of glycine from glyoxylate and glutamate or alanine.
Additional important mammalian routes for glycine formation
are from choline and from serine ( serine hydroxymethyl
transferase) reaction. (H4 folate,tetrahydrofolate.)
Serine
Oxidation of the -hydroxyl group of the glycolytic intermediate
3-phosphoglycerate by 3-phosphoglycerate dehydrogenase
converts it to 3-phosphohydroxypyruvate. Transamination and
subsequent dephosphorylation then forms serine .
Cysteine
While not nutritionally essential, cysteine is formed from
methionine, which is nutritionally essential. Following
conversion of methionine to homocysteine , homocysteine
and serine form cystathionine, whose hydrolysis forms
cysteine and homoserine.
E. Tyrosine
Tyrosine is formed from phenylalanine by phenylalanine hydroxylase.
The reaction requires molecular oxygen and the coenzyme
tetrahydrobiopterin.
One atom of molecular oxygen becomes the hydroxyl group of tyrosine,
and the other atom is reduced to water.
During the reaction, tetrahydrobiopterin is oxidized to dihydrobiopterin.
Tetrahydrobiopterin is regenerated from dihydrobiopterin in a separate
reaction requiring NADPH.
Hydroxyproline & Hydroxylysine
Hydroxyproline and hydroxylysine occur principally in
collagen. Since there is no tRNA for either hydroxylated amino
acid. Peptidyl hydroxyproline and hydroxylysine arise from
proline and lysine catalyzed by prolyl hydroxylase and lysyl
hydroxylase of skin, skeletal muscle, and granulating wounds.
But only after these amino acids have been incorporated
into peptides.
Requires: substrate, molecular O2, ascorbate, Fe2+, and α ketoglutarate . One atom of O2 is incorporated into proline or
lysine, the other into succinate. A deficiency of the vitamin C
required for these hydroxylases results in Scurvy.
Selenocysteine, the 21st Amino Acid
While its occurrence in proteins is uncommon, selenocysteine
is present at the active site of several human enzymes that
catalyze redox reactions. Examples include glutathione
peroxidase and the deiodinase that converts thyroxine to
triiodothyronine.
replacement of selenocysteine by cysteine can significantly
decrease catalytic activity.
Impairments in human selenoproteins have been implicated
in tumorigenesis and atherosclerosis, and are associated with
selenium deficiency cardiomyopathy .
Unlike hydroxyproline or hydroxylysine, selenocysteine arises
co-translationally during its incorporation into peptides.
Biosynthesis requires cysteine, selenate (SeO4-2), ATP, a
specific tRNA, and several enzymes. Serine provides the
carbon skeleton of selenocysteine.
METABOLIC DEFECTS IN AMINO ACID METABOLISM
Incidence of inherited disease of amino acid metabolism[cystinuria is the most
common genetic error of amino acid transport