CLINICAL CASES
351
Fates of tyrosine.
Tyrosine can be degraded by oxidative processes to ace-
toacetate and fumarate which enter the energy generating pathways of the citric
acid cycle to produce ATP as indicated in Figure 38-2. Tyrosine can be further
metabolized to produce various neurotransmitters such as dopamine, epineph-
rine, and norepinephrine. Hydroxylation of tyrosine by tyrosine hydroxylase
produces dihydroxyphenylalanine (DOPA). This enzyme, like phenylalanine
hydroxylase, requires molecular oxygen and tetrahydrobiopterin. As is the case
for phenylalanine hydroxylase, the tyrosine hydroxylase reaction is sensitive to
perturbations in dihydropteridine reductase or the biopterin synthesis pathway,
anyone of which could lead to interruption of tyrosine hydroxylation, an
increase in tyrosine levels, and an increase in transamination of tyrosine to form
its cognate a-keto acid, para-hydroxyphenylpyruvate, which also would appear
in urine as a contributor to phenylketonuria.
Tyrosine is also the precursor to melanin formation in melanocytes, the first
step of which is catalyzed by tyrosinase as shown in Figure 38-3. This reac-
tion is a two step reaction in which dihydroxyphenylalanine (DOPA) is an
intermediate in the formation of dopaquinone. Ring closure of the alanine por-
tion of dopaquinone forms a pyrrole ring and subsequent reactions give rise to
the melanins, the primary dark pigment associated with skin color being eume-
lanin. The absence of tyrosinase gives rise to classic albinism. Phenylalanine
is a competitive inhibitor with tyrosine for tyrosinase. Thus in a situation
wherein phenylalanine hydroxylase activity is deficient, not only does the a-keto
cognate transamination product phenylpyruvate increase but so also does the
level of phenylalanine. Thus, excess phenylalanine inhibits tyrosinase and
melanin formation resulting in hypopigmentation of skin and hair in affected
persons.
Figure 38-3. Conversion of tyrosine to dopaquinone by the enzyme tyrosi-
nase, a Cu+2-dependent enzyme in melanocytes.
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