Transcript Amino acids catabolism

AMINO ACIDS CATABOLISM
Amino acids act
principally as the
building blocks
and to the
synthesis of
variety of other
biologically
molecules.
When a.acids
deaminated
(removed the αamino group),
their C-keletons
can be fed to
TCA cycle.
They may be
used as
precursors of
other
biomolecules.
Fig. 23-1, p.630
How are amino acids synthesized?
Reductive amination
Amidation
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The α-amino group of glutamate and the side-chain amino
group of glutamine are shifted to other compounds:
transamination reactions
The biosynthesis of amino acids involves a common set of
reactions
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Glutamate is formed from NH4+ and α-ketoglutarate
in a reductive amination that requires NADPH. This
reaction is catalyzed by glutamate dehydrogenase
(GDH)
The conversion of Glutamate to Glutamine is
catalyzed by glutamine synthetase (GS) that requires
ATP
Combination of GDH and GS is responsible for most
assimilation of ammonia into organic compound.
However, the KM of GS is lower than GDH
Fig. 23-6, p.635
Transamination reactions: Role of Glutamate and
Pyridoxal phosphate
Amino acids biosynthesis

Enzyme that catalyzed transamination require pyridoxal
phosphate as coenzyme
Fig. 23-8b, p.637
Fig. 23-9, p.638
One-C transfer and the
serine-family
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In amino acid biosynthesis, the one-C transfer occurs
frequently
E.g serine family (also include glycine and cysteine)
Ultimate precursor of serine is 3-phosphoglycerate
(obtainable from glycolitic pathway)
The conversion of serine to glycine involves one-C
unit from serine to an acceptor
This is catalyzed by serine hydroxymethylase, with
pyridoxal phosphate as coenzyme
The acceptor is tetrahydropholate (derivative of
folic acid) – its structure has 3 parts: a subtituted
pteridine ring, p-aminobenzoic acid and glutamic
acid
Serine + tetrahydrofolate →
Glycine + methylenetetrahydrofolate +H2O
Fig. 23-12, p.641
The conversion of serine to cysteine involves some interesting reactions
In plants and bacteria: serine is acetylated to form O-acetylserine (by serine
acyltransferase, and acetyl-CoA as acyl donor)
Fig. 23-13, p.641
Fig. 23-14, p.641
In animals: the reaction involves the
amino acid methionine
Methionine (produced by reactions of
the aspartate family) in bacteria and
plants can be obtained from dietary
sources – essential amino acids
Fig. 23-16, p.642
What are essential amino acids?
• The biosynthesis of proteins requires the presence of all 20 amino
acids
• If one is missing or in short supply, the protein biosynthesis is
inhibited
• Protein deficiency will lead to the disease kwashiorkor; severe in
growing children, not simply starvation but the breakdown of the
body’s own protein
Table 23-1, p.643
Catabolism of amino acids
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In catabolism, the amino nitrogen of original amino
acid is transferred to α-ketoglutarate → glutamate,
leave behind the C skeletons
Disposition of C skeletons
There are two pathways of the breakdown of C skeletons
depends on type of end product:
 i. Glucogenic amino acid: yields pyruvate and OAA on
degradation (can be converted to glucose with OAA as
intermediate)
 Ii. Ketogenic amino acid: one that breaks down to acetylCoA or acetoacetyl-CoA to form ketone bodies

Table 23-2, p.644
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Excretion of excess nitrogen
Excess nitrogen is excreted in one
of three forms: ammonia, urea
and uric acid
 Animal in aquatic env.: release as
ammonia
 Terrestrial animal: urea (soluble in
water)
 Birds: uric acid (insoluble in
water)
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Fig. 23-17, p.644
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Urea cycle
 Central pathway in
nitrogen metabolism
 The nitrogen that enter
urea cycle come from
several sources
 A condensation reaction
bet. ammonium ion and
CO2 produce
carbamoyl phosphate
in a reaction that
requires of two
molecules of
ATP/carbamoyl
phosphate
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In human, urea synthesis is
used to excrete excess
nitrogen, after consuming
a high-protein meal
The pathway is confined
to the liver
The synthesis of fumarate
is a link bet. the urea
cycle and TCA cycle
p.646a
When amino acid catabolism is high, large
amounts of glutamate will be present from
degradation of glutamine, from synthesis via
glutamate dehydrogenase and from
transamination reaction.
Increase glutamate level leads to increase
levels of N-acetylglutamate followed by
increasing the urea cycle activity.
p.648