PathwayStep2471 PathwayStep2470 PathwayStep2465 PathwayStep2466 PathwayStep2467 PathwayStep2468 PathwayStep2469 PathwayStep2464 PathwayStep2463 PathwayStep2462 Phenylalanine and tyrosine catabolism Authored: D'Eustachio, P, 2003-06-24 00:00:00 Edited: D'Eustachio, P, 2003-06-24 00:00:00 GENE ONTOLOGYGO:0006559 ISBN0079130356 Reactome Database ID Release 4371182 Reactome, http://www.reactome.org ReactomeREACT_1786 The first reaction in this pathway converts phenylalanine to tyrosine, coupled to the conversion of tetrahydrobiopterin to 4a-hydroxytetrahydrobiopterin, catalyzed by phenylalanine hydroxylase. (Deficiencies in this enzyme are responsible for the commonest form of phenylketonuria (PKU) in humans.) This reaction functions both as the first step in the pathway by which the body disposes of excess phenylalanine, and as a source of the amino acid tyrosine. The next two reactions are responsible for the regeneration of tetrahydrobiopterin from 4a-hydroxytetrahydrobiopterin. The following five reactions convert tyrosine to fumarate, an intermediate in the citric acid cycle, and acetoacetate, a ketone body. q-dihydrobiopterin + NADH + H+ => tetrahydrobiopterin + NAD+ tyrosine + alpha-ketoglutarate <=> p-hydroxyphenylpyruvate + glutamate p-hydroxyphenylpyruvate + glutamate <=> tyrosine + alpha-ketoglutarate p-hydroxyphenylpyruvate + O2 => homogentisate + CO2 homogentisate + O2 => maleylacetoacetate maleylacetoacetate => fumarylacetoacetate fumarylacetoacetate => fumarate + acetoacetate phenylalanine + tetrahydrobiopterin + O2 => tyrosine + 4a-hydroxytetrahydrobiopterin + H2O phenylalanine + pyruvate => 3-(indol-3-yl)pyruvate + alanine 4a-hydroxytetrahydrobiopterin => q-dihydrobiopterin + H2O