adrenal medulla. Dopamine, the other catecholamine, whose synthesis takes place in cholinergic neurons, is a precursor for both norepinephrine and epinephrine but its roles are distinct. Catecholamine synthesis and the activities of its enzymes are regulated by neuronal and humoral mechanisms. The precursor of all catecholamines is L-tyrosine which can be derived from the diet or from the hydroxylation of L-phenylalanine. Tyrosine hydroxylase (Th), an iron-containing, biopterin-dependent soluble enzyme catalyzes the conversion of tyrosine to dihydroxy-L-phenylalanine (L-DOPA) in the rate-limiting step of the reaction. The cofactor tetrahydrobioterin (BH4) is used in the reaction and the resulting dihydrobiopterin (BH2) is reconverted to BH4 by dihydropteridine reductase. Tetrahydrobiopterin can also be synthesized de novo from the purine nucleotide GTP. The short term control of TH activity is due to product(s)-based inhibitory feedback and activation by phosphorylation; several kinases and phosphatases have been implicated in modulating the activity of the enzyme. Long term control involves regulation of transcription, stability and in humans, alternative splicing. L-DOPA is converted to dopamine (DA) by the pyridoxal phosphate-dependent aromatic L-amino acid decarboxylase (Ddc). Both Th and Ddc interact with vesicle protein Slc182a, which couples DA synthesis with transport into vesicles. DA is stored in vesicles where it can be converted to norepinephrine by Dbh, a copper- and ascorbate-dependent enzyme that is found either in a soluble or as a membrane-bound form within storage vesicles. To see the ontology report for GViewer, annotations and download, click here
[Click to see the ontology report for related GO term - GO:0042421 and entry at Reactome - REACT 15442.1]...(less)