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CASE FILES: BIOCHEMISTRY
also catalyze the reverse reaction to produce Glu, but in this case it uses the
reducing equivalents from NADPH instead of NADH. The oxidative deami-
nation reaction is allosterically activated by adenosine diphosphate (ADP) and
guanosine diphosphate (GDP), whereas the reductive amination is activated by
GTP and adenosine triphosphate (ATP). The overall process for net removal of
the amino group from a-amino acids is summarized in Figure 37-1.
Ammonia is produced by almost all cells in the body; however, only the
liver has the enzymatic machinery to convert it to urea. Therefore, extra-
hepatic ammonia must be transported to the liver. However, ammonia in the
blood is toxic to cells, and therefore the nitrogen from amino acid catabolism
is transported in blood either as glutamine or alanine. Glutamine is synthesized
from Glu and ammonia in an ATP-requiring reaction that is catalyzed by glu-
tamine synthetase. Alanine is formed from pyruvate in a transamination reac-
tion catalyzed by alanine transaminase (ALT).
Glutamine and alanine are transported to the liver in the blood, where they
are taken up by cells in the periportal region. Ammonia is released by the com-
bined action of ALT (in the case of alanine), glutaminase (in the case of glut-
amine) and GDH. The a-amino group of alanine is transferred to a-KG to
form Glu and pyruvate. Glutaminase catalyzes the hydrolysis of the side-chain
amide group releasing ammonia and Glu. Ammonia and Glu enter the mito-
chondria, where Glu is oxidatively deaminated by GDH. The ammonia that is
released by glutaminase and GDH then enters the urea cycle (Figure 37-2),
which includes enzymes that are located both in the mitochondria and the
cytosol.
Ammonia is condensed with bicarbonate and ATP in the mitochondrion to
form carbamoyl phosphate in a reaction catalyzed by carbamoyl phosphate
synthetase I. Two molecules of ATP are used in this reaction; one provides the
phosphate, and the other is hydrolyzed to ADP and inorganic phosphate (Pi) to
provide the energy that drives the reaction to products. The activated carbamoyl
group is then transferred to the amino acid ornithine by the mitochondrial
enzyme ornithine transcarbamoylase to form citrulline. Citrulline then is trans-
ported out of the mitochondrion to the cytosol, where the rest of the reactions
Figure 37-1. Summary of amino acid catabolism.
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