PathwayStep4231 PathwayStep4232 PathwayStep4233 phenylalanine + oxaloacetate => phenylpyruvate + aspartate [CCBL1] phenylalanine + H2O + O2 => phenylpyruvate + NH3 + H2O2 phenylpyruvate + NADH + H+ => phenyllactate + NAD+ PathwayStep2481 PathwayStep2463 Abnormal metabolism in phenylketonuria Authored: D'Eustachio, P, 2012-03-04 Edited: D'Eustachio, P, 2012-03-16 Phenylalanine hydroxylase (PAH) catalyzes the conversion of phenylalanine to tyrosine. In the absence of functional PAH, phenylalanine accumulates to high levels in the blood (Mitchell and Scriver 2010) and is converted to phenylpyruvate and phenyllactate (Clemens et al. 1990; Langenbeck et al. 1992). The extent of these conversions is modulated by genetic factors distinct from PAH, as siblings with the identical PAH defect can produce different amounts of them (Treacy et al. 1996).<p>Both L-amino acid oxidase (Boulland et al. 2004) and Kynurenine--oxoglutarate transaminase 3 (Han et al. 2004) can catalyze the conversion of phenylalanine to phenylpyruvate and lactate dehydrogenase can catalyze the conversion of the latter molecule to phenyllactate (Meister 1951). Elevated levels of phenylalanine, phenylpyruvate, and phenyllactate are all thought to contribute to the symptoms of phenylketonuria. One possible target is the metabolism of kynurenine. Pubmed15606768 Pubmed1583868 Pubmed17356132 Pubmed20301677 Pubmed2116554 Pubmed8892014 Reactome Database ID Release 432160456 Reactome, http://www.reactome.org ReactomeREACT_121117 Reviewed: Jassal, B, 2012-03-16 kynurenine + pyruvate => 4-(2-aminophenyl)-2,4-dioxobutanoic acid + alanine [CCBL1] phenylalanine + tetrahydrobiopterin + O2 => tyrosine + 4a-hydroxytetrahydrobiopterin + H2O