Phenylalanine Metabolism: Phenylketonuria

The hydroxylase is a trimer of approximately 150 kDa of identical subunits and is located predominantly in the liver. The enzyme has been mapped to human chromosome 12q22-24.1, where the gene comprises 13 exons extending over 90 kb of genomic DNA. Deletions in the gene are not common. A frequent cause among northern Europeans (~40%) is a G-to-A transition at the 5′ donor splice site in intron 12, resulting in absence of the Cterminus. Another relatively common (~20%) mutation in northern Europeans involves a C-to-T transition in exon 12, resulting in substitution of a tryptophan for an arginine residue. Over 70 different mutations have been described to date in the American population.