CLINICAL CASES
341
D efinitions
Glutamate dehydrogenase: A mitochondrial enzyme present in all tissues
that metabolizes amino acids. It catalyzes the oxidative deamination of
glutamate to a-ketoglutarate using NAD+ as the electron acceptor to also
produce nicotinamide adenine dinucleotide (NADH) and ammonia. The
enzyme uses the reducing equivalents of nicotinamide adenine dinu-
cleotide phosphate (NADPH) to perform the reverse reaction.
Ornithine: An a-amino acid similar in structure to lysine but having one
methylene group less in the side chain. It is carbamoylated to form cit-
rulline to begin the urea cycle and is regenerated in the final step that
releases urea.
Transaminase: An aminotransferase; a pyridoxal phosphate-requiring
enzyme that transfers an amino group from an a-amino acid to an a-keto
acid.
Urea cycle: The series of reactions that occur in the liver to synthesize urea
for the excretion of nitrogen. The two nitrogen atoms present in urea
arise from ammonium ion and the a-amino group of aspartate. The cycle
also requires CO
2
(HCO-) and the expenditure of four high-energy phos-
phate bonds and produces fumarate.
D ISC U SSIO N
Amino acids differ from carbohydrates and fats in that they contain nitrogen
as part of their molecular structure. For the carbons in amino acids to enter into
the energy generating metabolic pathways, the amino groups must first be
removed so that they can be detoxified and excreted. The amino acid nitrogen
is excreted predominantly as urea, but some is also excreted as free ammonia
in order to buffer the urine.
The first step in the catabolism of most amino acids is the transfer of the
a-amino group from the amino acid to a-ketoglutarate (a-KG). This
process is catalyzed by transaminase (aminotransferase) enzymes that require
pyridoxal phosphate as a cofactor. The products of this reaction are glutamate
(Glu) and the a-ketoacid analog of the amino acid destined for catabolic
breakdown. For example, aspartate is converted to its a-keto analog, oxalo-
acetate, by the action of aspartate transaminase (AST), which also produces
Glu from a-KG. The transamination process is freely reversible, and the direction
in which the reaction proceeds is dependent on the concentrations of the reactants
and products. These reactions do not effect a net removal of amino nitrogen;
the amino group is only transferred from one amino acid to another.
For net removal of amino nitrogen, a second enzymatic reaction must take
place that removes the amino group from Glu for disposal. The net removal of
the amino nitrogen is accomplished by the mitochondrial enzyme glutamate
dehydrogenase (GDH), which catalyzes the oxidative deamination of Glu to
a-KG in a reaction that uses NAD+ as the electron acceptor. The enzyme can
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