CLINICAL CASES
353
[38.2]
A. The correct response is dihydropteridine reductase. This enzyme
reduces dihydrobiopterin to tetrahydrobiopterin the obligate electron
donor for phenylalanine hydroxylase. Tyrosinase is the first enzyme on
the pathway to melanin. Dopamine hydroxylase and tyrosine transam-
inase are enzymes on other tyrosine metabolic tracts. Homogentisic
acid oxidase is an enzyme on the pathway of tyrosine to fumarate and
acetoacetate.
[38.3]
B. Excess phenylalanine inhibits tyrosinase the first step toward melanin
production, thus resulting in hypopigmentation. Excess melanin leads to
hyperpigmentation. Melatonin is a hormone involved in the sleep cycle.
Excessive stimulation of tyrosinase would lead to more melanin and
therefore hyperpigmentation.
Para
-hydroxyphenylpyruvate means less
transamination and perhaps more tyrosine converted to melanin and
hyperpigmentation.
B IO C H E M IS T R Y PE A R L S
Phenylketonuria (PKU) is an autosomal recessive disorder of amino
acid metabolism affecting approximately
1
/
10 ,0 0 0
of infants in
the North America.
It is most often due to deficiency of the enzyme phenylalanine
hydroxylase which causes the accumulation of harmful metabo-
lites, including phenylketones.
The gene for phenylalanine hydroxylase is located on chromosome
12 at band region q 23.2.
If untreated, PKU leads to mental retardation, seizures, psychoses,
eczema, and a distinctive “mousy” odor.
Phenylketonuria is a disease readily diagnosable in childhood and it
is important for an optimal clinical outcome for it to be diagnosed
as early as possible.
REFERENCES
Scriver CR, Beaudet AL, Sly WS, et al. The Metabolic and Molecular Basis of
Inherited Disease, 8th ed, New York: McGraw Hill, 2001:1667-776.
Devlin TM, ed. Text Book of Biochemistry with Clinical Correlations, 5th edition,
New York: Wiley-Liss, 2002:797-9, 881-2.
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