3. 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.
Fig. 23-1, p.630
4. How are amino acids
synthesized? Reductive
amination
Amidation
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
5. 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
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
14. 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
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
18. 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
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
21. 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)
Fig. 23-17, p.644
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
CO2 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
25. 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
Editor's Notes
Root nodules of leguminous plants play a pivotal role in nitrogen fixation.
FIGURE 23.1 The flow of nitrogen in the biosphere.
FIGURE 23.5 (a) The production of glutamate from -ketoglutarate. (b) The production of glutamine from glutamate.
FIGURE 23.6 Families of amino acids based on biosynthetic pathways. Each family has a common precursor.
FIGURE 23.7 The relationship between amino acid metabolism and the citric acid cycle.
FIGURE 23.8 The role of pyridoxal phosphate in transamination reactions. (a) The mode of binding of pyridoxal phosphate (PyrP) to the enzyme (E) and to the substrate amino acid.
FIGURE 23.8 The role of pyridoxal phosphate in transamination reactions. (b) The reaction itself. The original substrate, an amino acid, is deaminated, while an -keto acid is aminated to form an amino acid. The net reaction is one of transamination. Note that the coenzyme is regenerated and that the original substrate and final product are both amino acids.
FIGURE 23.9 Transamination reactions switch an amino group from one amino acid to an -keto acid. Glutamate and -ketoglutarate ( -KG) are one donor/acceptor pair. Above, a general case. Below, a specific case, in which the other donor/acceptor pair is aspartate and oxaloacetate.
FIGURE 23.10 The biosynthesis of serine.
FIGURE 23.11 (a) The structure of folic acid, shown in nonionized form. (b) The reactions that introduce one-carbon units into tetrahydrofolate (THF) link seven different folate intermediates that carry one-carbon units in three different oxidation states (-2, 0, and +2). ( Adapted from T. Brody et al., in L. J. Machlin. Handbook of Vitamins. New York: Marcel Dekker, 1984. )
Figure 23.12 The conversion of serine to glycine, showing the role of tetrahydrofolate.
FIGURE 23.13 The biosynthesis of cysteine in plants and bacteria.
FIGURE 23.14 Electron transfer reactions of sulfur in plants and bacteria.
FIGURE 23.15 The structure of S -adenosylmethionine (SAM), with the structure of methionine shown for comparison.
FIGURE 23.16 The biosynthesis of cysteine in animals. (A stands for acceptor.)
FIGURE 23.17 Nitrogen-containing products of amino acid catabolism.
FIGURE 23.18 The urea cycle series of reactions: Transfer of the carbamoyl group of carbamoyl-P to ornithine by ornithine transcarbamoylase (OTCase, reaction 1) yields citrulline. The citrulline ureido group is then activated by reaction with ATP to give a citrullylOAMP intermediate (reaction 2a); AMP is then displaced by aspartate, which is linked to the carbon framework of citrulline via its -amino group (reaction 2b). The course of reaction 2 was verified using 18O-labeled citrulline. The 18O label (indicated by the asterisk, *) was recovered in AMP. Citrulline and AMP are joined via the ureido *O atom. The product of this reaction is argininosuccinate; the enzyme catalyzing the two steps of reaction 2 is argininosuccinate synthetase. The next step (reaction 3) is carried out by argininosuccinase, which catalyzes the nonhydrolytic removal of fumarate from argininosuccinate to give arginine. Hydrolysis of arginine by arginase (reaction 4) yields urea and ornithine, completing the urea cycle.
FIGURE 23.19 The urea cycle and some of its links to the citric acid cycle. Part of the cycle takes place in the mitochondrion and part in the cytosol. Fumarate and aspartate are the direct links to the citric acid cycle. Fumarate is a citric acid cycle intermediate. Aspartate comes from transamination of oxaloacetate, which is also a citric acid cycle intermediate.
A kangaroo rat converts some of its waste nitrogen to uric acid.
