CASE FILES: BIOCHEMISTRY
Phenylalanine hydroxylation reaction and its components.
As shown in
Figure 38-2 the phenylalanine hydroxylation reaction is the pathway whereby
dietary phenylalanine can be converted into tyrosine relieving some of the
dietary requirement for tyrosine. It is catalyzed by phenylalanine hydroxylase,
a monooxygenase requiring molecular oxygen (O2) and a specific two electron
donor tetrahydrobiopterin. One atom of molecular oxygen appears in the prod-
uct tyrosine as a hydroxyl group in the
position, the remaining oxygen
atom appearing in the product water.
The provision of reducing equivalents to phenylalanine hydroxylase is
dependent on reduction of dihydrobiopterin by NADH catalyzed by the
enzyme dihydropteridine reductase, as shown in Figure 38-2. This reduction is
dependent on the availability of biopterin and therefore on the biopterin syn-
thetic pathway. Thus any genetic or protein folding defect in either dihy-
dropteridine reductase or the biopterin biosynthetic
compromise the efficacy of phenylalanine hydroxylation to tyrosine resulting
in hyperphenylalaninemia and also phenylketonuria resulting from increase
transamination of phenylalanine to phenylpyruvate.
The principal of enzyme in this pathway is phenylalanine hydroxylase. The
gene for phenylalanine hydroxylase is located on chromosome
region q 23.2 and comprises 100 kb of genomic DNA. Several hundred alleles
causing disease states have been recognized for this gene, more than 60 percent
of which are classified as missense alleles. European and Chinese populations
show an order of magnitude higher incidence than persons of African descent.
This population specific expression of disease causing alleles may explain the
wide range of incidence reported for this disease entity (5 to 350 cases/million
Figure 38-2. Normal conversion of phenylalanine into the amino acid tyrosine
catalyzed by phenylalanine hydroxylase.