CLINICAL CASES
343
Aspartate
Carbamoyl phosphate
synthetase I
HoN —C —0 — P —O'
+ 2 ADP + 1 Pj
Urea
Carbamoyl phosphate
Ornithine
Ornithine
Argmase
transcarbamoylase
Arginine
Citrulline
Argininosuccinase
Argininosuccinate J ' "
Aspartate
+ ATP
synthetase y
Arginmosuccinate
Fumarate
AMP + PP
L
► 2P
Net:
C O O
CHj
coo
HC
I
coo
Urea
Fum arate
Figure 37-2. Urea cycle.
that are required to synthesize urea take place. The second nitrogen of urea
comes directly from the amino acid aspartate. The side chain of citrulline con-
denses with the a-amino group of aspartate to form arginmosuccinate in a
reaction that is thermodynamically driven by the conversion of ATP to AMP
and inorganic pyrophosphate (PPi). The rapid hydrolysis of PPi by pyrophos-
phatase releases energy and removes the PPi, thus making the formation of
argininosuccinate thermodynamically irreversible. Argininosuccinate is then
cleaved to arginine and fumarate by argininosuccinase (argininosuccinate
lyase). Arginase then hydrolyzes the guanidino group of arginine, releasing
urea and regenerating ornithine, which can then reenter the mitochondrion and
accept another carbamoyl group from carbamoyl phosphate. The urea is trans-
ported to the kidney for excretion.
Glutamine is also used by the kidney as a source of ammonia that is used
to buffer the urine. Ammonia is released from glutamine by the same enzymes
that are active in the liver. The free ammonia accepts a proton to form ammo-
nium ion, thus decreasing the acidity of the urine.
Although most of the ammonia detoxified by the liver arises from the
breakdown of amino acids in dietary protein or endogenous protein that is
being turned over, ammonia is also produced by bacteria in the gut. This is
absorbed into the portal venous blood and taken directly to the liver for con-
version into urea.
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