[15.2] A 3-month-old male infant developed seizures and progressively wors-
ened, showing hypotonia, psychomotor retardation, and poor head con-
trol. He had lactic acidosis and an elevated plasma pyruvate level, both
more than seven times the normal amount. Pyruvate carboxylase activity
was measured using extracts of fibroblasts and was found to be less
than 1 percent of the normal level. Oral administration of which of the
following amino acids would you recommend as the best therapy for
this patient?
A. Alanine
B. Glutamine
C. Leucine
D. Lysine
E. Serine
[15.3] A deficiency in thiamine (vitamin B1) would most likely lead to which
of the following clinical manifestations?
A. A decrease in carboxylase enzyme activity
B. A decrease in serum lactate concentrations
C. A decrease in red blood cell transketolase activity
D. An increase in urinary methylmalonate
E. An increase in prothrombin time
A nsw ers
D. The increased concentrations of pyruvate, lactate, and alanine
indicate that there is a block in the pathway leading from pyruvate
toward the TCA cycle. A deficiency in pyruvate dehydrogenase
would lead to a buildup of pyruvate. Pyruvate has three fates other
than conversion to acetyl-CoA by pyruvate dehydrogenase: conver-
sion to oxaloacetate by pyruvate carboxylase, reduction to lactate by
lactate dehydrogenase, and transamination to the amino acid alanine.
Thus, because pyruvate builds up, an increase in lactate and alanine
would be expected if pyruvate dehydrogenase was deficient.
B. A deficiency in pyruvate carboxylase results in a diminution of
oxaloacetate, the C4 acid that acts as the acceptor for an acetyl group
from acetyl-CoA. In order for the TCA cycle to continue efficiently,
C4 acids must be replenished. Amino acids whose carbon skeletons
feed into the TCA cycle and increase the C4 pool will accomplish
this. Glutamine, which is converted to a-ketoglutarate, will lead to an
increase in all of the C4 acids (succinate, fumarate, malate, and
oxaloacetate). Alanine and serine are converted to pyruvate, which as
a result of the deficiency in pyruvate carboxylase will not increase the
C4 pool. Lysine and leucine are ketogenic amino acids and thus also
do not increase the C4 pool.
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