DA biosynthesis and degradation

DA biosynthesis and degradation. The major pathway for DA biosynthesis starts at tyrosine or phenylalanine which can be hydroxylated by phenylalanine hydroxylase. Tyrosine is hydroxylated to form DOPA, now bearing the catechol moiety, by BH4-dependent tyrosine hydroxylase or alternatively by tyrosinase. Decarboxylation of DOPA by AADC leads then to DA. In another pathway for DA synthesis AADC action occurs before the hydroxylation at the aromatic ring. Tyramine is then oxidized by Cyp2D. Besides being a neurotransmitter itself, DA is also the precursor of epinephrine and norepinephrine. DA degradation is performed by COMT, MAO, ADH, ALDH and AR in variable order leading to DOPAC and HVA as the main endproducts. Phenolsulfotransferases and uridine diphosphoglucuronosyltransferases catalyze conjugation reactions with phosphate and glucuronic acid respectively. The relative contributions of the different enzymes are strongly species-, tissue- and celltype-dependent. The depicted reactions may occur in distinct compartments.

Publication

Complexity of dopamine metabolism. (2013) Johannes Meiser, et al. Cell Commun Signal. 2013;11:34-34. Figure: F2. All organisms Drosophila melanogaster Mus musculus Sus scrofa Homo sapiens Rattus norvegicus Canis lupus familiaris Cavia porcellus Bos taurus Danio rerio

Disease mentions