CASE FILES: BIOCHEMISTRY
As part of a standard neonatal screen, an infant is diagnosed with a loss
of function genetic defect in the enzyme phenylalanine hydroxylase.
Defects in this enzyme can result in a condition known as phenylke-
tonuria (PKU), which results from the toxic effects of phenylalanine
derived phenylketones. Fortunately, this condition can be managed by
regulating the amount of phenylalanine provided in the diet. Which of
the following nonessential amino acids will need to be supplied in the
diet of this infant?
A nsw ers
C. Methionine can be synthesized by the methylation of homocys-
teine by the enzyme methionine synthase, which requires the partici-
pation of vitamin B12 and 5-methyltetrahydrofolate. It is actually the
homocysteine component of methionine that is required, since this
reaction has the capacity to synthesize enough methionine. However,
there is no good dietary source of homocysteine. This conversion of
homocysteine to methionine also serves the purpose of making THF
available for other biosynthetic reactions.
B. Arginine is considered nonessential because biosynthetic path-
ways for its generation do exist in certain cells of the body. Arginine
is synthesized from the amino acid glutamate. Glutamate is first con-
verted to ornithine, which is then converted to arginine by enzymes
of the urea cycle. The urea cycle is found only in the liver, and thus
the production of arginine through this pathway is limiting. The pro-
duction of arginine through this pathway is likely sufficient for
healthy adults, but it may not be sufficient in times of growth where
increased protein synthesis augments the need for amino acids. Thus,
in growing children and in adults following surgery, arginine
becomes an essential amino acid.
E. Phenylalanine is an essential amino acid that is also used to gen-
erate the nonessential amino acid tyrosine. Because tyrosine is made
from phenylalanine, it becomes an essential amino acid when pheny-
lalanine levels are limited because of the absence of phenylalanine