Plants and bacteria synthesize all twenty amino acids, whereas,

most other organisms obtain at least some of the required amino

acids from their diet. Humans can only synthesize about half of
the twenty amino acids.
In general, the more complex amino acids are essential amino
acids in humans as they require enzymes that have been lost from
Biosynthesis of Amino Acids
acids in humans as they require enzymes that have been lost from
the human genome over evolutionary time.
Most animals are much more restricted in their ability to
synthesize amino acids de novo because they lack many of the
required enzymes.
The carbon skeletons of all twenty amino acids are derived
from just seven metabolic intermediates, that together, are
found in three metabolic pathways. These include:
1) three glycolytic pathway intermediates; 3-
phosphoglycerate, phosphoenolypyruvate, and pyruvate,
Biosynthesis of Amino Acids
phosphoglycerate, phosphoenolypyruvate, and pyruvate,
2) two pentose phosphate pathway intermediates; ribose 5-
phosphate and erythrose 4-phosphate
3) two citrate cycle intermediates; -ketoglutarate and
oxaloacetate.
Overview of Amino
Acid Biosynthesis
The carbon skeleton precursors
derive from three sources:
glycolysis (pink), the
citric acid cycle (blue), and the
pentose phosphate pathway pentose phosphate pathway
(purple).
Biosynthesis of amino acids (AA)
Humans can synthesize only 10
of the 20 AA.
Essential AA : AA that cannot be
synthesized de novo. They must be
obtained from diet.
Nonessential AA:
Can be synthesized in the human. Can be synthesized in the human.
The 20 a.a. do not include hydroxy
proline and hydroxy lysine.
Arginine is essential in young
children not in adults.
Thus mammals can synthesize only
13 a.a ( 10 non-essential +arginine +
hydroxy proline + hydroxy lysine )
Liver is the main site for
biosynthesis of non-essential a.a.
Arginine is listed as an essential amino acid because humans require
arginine in their diet to support rapid growth during childhood and
pregnancy. However, arginine is actually generated from argininosuccinate
in the urea cycle, which means that a small amount of this "essential"
amino acid is made available for protein synthesis through this route.
Tyrosine is also a conditional nonessential amino acid is made in humans
Overview of Amino Acid Biosynthesis
Tyrosine is also a conditional nonessential amino acid is made in humans
from the essential amino acid phenylalanine by the enzyme phenylalanine
hydroxylase. Therefore, as long as we have enough phenylalanine in our
diets we can generate tyrosine, although in fact, much of the tyrosine in our
bodies actually comes directly from dietary tyrosine.
Amino Acid Biosynthetic Families,
Grouped by Metabolic Precursors
Amino acids are
grouped into six families
according to their
metabolic precursors.
-Ketoglutarate as a Precursor
4 amino acids are synthesized from -Ketoglutarate .
3 non-essential: glutamate, glutamine and proline.
One essential: Arginine.
- Glutamate biosynthesis:
Glutamate is synthesized by
transfer of an amino group
to -ketoglutarate.
Glutamate can also be
synthesized by the reverse synthesized by the reverse
of oxidative deamination,
catalyzed by glutamate
dehydrogenase ( reductive
amination of -
ketoglutarate).
- Glutamine biosynthesis:
Glutamine is formed
from glutamate by
glutamine synthetase.
The reaction is driven
by the hydrolysis of ATP. by the hydrolysis of ATP.
Glutmine synthetase is
a mitochondrial enzyme
found in many tissues
mainly brain and
kidney.
Proline biosynthesis:
Proline is synthesized through 2 pathways, both
occur in mammals.
Proline Glutamate is converted to proline by
cyclization and reduction reactions.
In the first step of proline synthesis, ATP reacts In the first step of proline synthesis, ATP reacts
with the -carboxyl group of glutamate to form an
acyl phosphate, which is reduced by NADPH or
NADH to glutamate -semialdehyde.
This intermediate undergoes rapid spontaneous
cyclization and is then reduced further to yield
proline.
Proline biosynthesis from glutamate
The second pathway for proline biosynthesis from
arginine by reversible pathway of proline catabolism.
(proline oxidase reaction is reversible)
Arginine biosynthesis:
In mammals arginine is synthesized from glutamate via urea cycle.
In bacteria, arginine is synthesized from glutamate in pathway
different from urea cycle in mammals because most bacteria do not
have arginase; not form ornithine from arginine .
Ornithine could also be synthesized from glutamate
-semialdehyde by transamination, but the spontaneous -semialdehyde by transamination, but the spontaneous
cyclization of the semialdehyde in the proline pathway precludes a
sufficient supply of this intermediate for ornithine synthesis.
Bacteria have a de novo biosynthetic pathway for ornithine (and
thus arginine) that parallels some steps of the proline pathway but
includes two additional steps that avoid the problem of the
spontaneous cyclization of glutamate semialdehyde.
3-Phosphoglycerate as a Precursor
3-Phosphoglycerate is an intermediate of glycolysis.
3 non-essential a.a. are synthesized from 3-
phosphoglycerate: serine, glycine and cystein.
Serine biosynthesis:
The major pathway for the formation of serine is the same
in all organisms.
3-phosphoglycerate is first oxidized to 3 phosphopyruvate,
and then transaminated to 3-phosphoserine.
In the first step, the hydroxyl group of 3-phosphoglycerate In the first step, the hydroxyl group of 3-phosphoglycerate
is oxidized by adehydrogenase (using NAD) to yield 3-
phosphohydroxypyruvate.
Transamination from glutamate yields 3-phosphoserine,
which is hydrolyzed to free serine by phosphoserine
phosphatase.
Biosynthesis of serine from 3-
phosphoglycerate and
of glycine from serine in all organisms.
Glycine is also made from
CO2 and NH4 by the action of glycine
synthase, with N5,N10-
methylenetetrahydrofolate
as methyl group donor. as methyl group donor.
Glycine biosynthesis:
Serine (three carbons) is the precursor of glycine (two
carbons) through removal of a carbon atom by serine
hydroxymethyltransferase .
Tetrahydrofolate accepts the carbon (C-3) of serine,
which forms a methylene bridge between N-5 and N-
10 to yield N5,N10-methylenetetrahydrofolate. 10 to yield N5,N10-methylenetetrahydrofolate.
The overall reaction, which is reversible, also requires
pyridoxal phosphate.
In the liver of vertebrates, glycine can be made by
another route catalyzed by glycine synthase (also
called glycinecleavage enzyme):
Biosynthesis of cysteine from
homocysteine and serine in
mammals.
The homocysteine is formed from
Biosynthesis of cysteine:
The homocysteine is formed from
methionine, as described befor.
Homocysteine gives the sulfur
atom and serine gives the carbon
skeleton.
Biosynthesis of cysteine:
In plants and bacteria cysteine is synthesized
from serine by different pathway.
Plants and bacteria produce the reduced
sulfur required for the synthesis of cysteine sulfur required for the synthesis of cysteine
from environmental sulfates.
The sulfide is then used in formation of
cysteine from serine in a two-step pathway
Two molecules of ATP are used for each
molecule of cysteine synthesized.