BCM311 - Amino Acids Catabolism

3. Fig. 23-1, p.630
Amino acids act
principally as the
building blocks
and to the
synthesis of
variety of other
biologically
molecules.
When a.acids
deaminated
(removed the α-
amino group),
their C-keletons
can be fed to
TCA cycle.
They may be
used as
precursors of
other
biomolecules.

4. How are amino acids
synthesized?
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
Reductive
amination
Amidation

5. Glutamate is formed from NH
4
+
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 K
M
of GS is lower than
GDH

6. Fig. 23-6, p.635

7. Transamination reactions: Role of Glutamate
and Pyridoxal phosphate
Amino acids
biosynthesis

8. Enzyme that catalyzed transamination require pyridoxal
phosphate as coenzyme

9. Fig. 23-8b, p.637

10. Fig. 23-9, p.638

11. One-C transfer and the
serine-family
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

13. Fig. 23-12, p.641
Serine + tetrahydrofolate →
Glycine + methylenetetrahydrofolate +H
2
O

14. Fig. 23-13, 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)

15. Fig. 23-14, p.641

16. 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

17. Fig. 23-16, p.642

18. Table 23-1, p.643
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

19. Catabolism of amino acids
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
acetyl-CoA or acetoacetyl-CoA to form ketone
bodies

20. Table 23-2, p.644

21. Fig. 23-17, p.644
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)

22. Urea cycle
Central pathway in
nitrogen metabolism
The nitrogen that
enter urea cycle
come from several
sources
A condensation
reaction bet.
ammonium ion and
CO
2
produce
carbamoyl
phosphate in a
reaction that requires
of two molecules of
ATP/carbamoyl
phosphate

23. 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

24. p.646a

25. p.648
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.