Central nervous system gene methylation

The general scheme of the biosynthesis of catecholamines was first postulated in 1939 (29) and finally confirmed in 1964 (Fig. 2) (30). Although not shown in Figure 2, in some cases the amino acid phenylalanine [63-91-2] can serve as a precursor it is converted in the liver to (-)-tyrosine [60-18-4] by the enzyme phenylalanine hydroxylase. Four enzymes are involved in E formation in the adrenal medulla and certain neurons in the brain tyrosine hydroxylase, dopa decarboxylase (also referred to as L-aromatic amino acid decarboxylase), dopamine-P-hydroxylase, and phenylethanolamine iV-methyltransferase. Neurons that form DA as their transmitter lack the last two of these enzymes, and sympathetic neurons and other neurons in the central nervous system that form NE as a transmitter do not contain phenylethanolamine N-methyl-transferase. The component enzymes and their properties involved in the formation of catecholamines have been purified to homogeneity and their properties examined. The human genes for tyrosine hydroxylase, dopamine- 3-oxidase and dopa decarboxylase, have been cloned (31,32). It is anticipated that further studies on the molecular structure and expression of these enzymes should yield interesting information about their regulation and function. 

NO is a gaseous neurotransmitter implicated in signaling in the central and peripheral nervous system as well as in the immune system and the vasculature. NO is formed from L-arginine by nitric oxide synthase (NOS). There are three isoforms of NOS. All isoforms require NADPH as a cofactor, use L-arginine as a substrate, and are inhibited by Nw-nitro-L-arginine methyl ester (L-NAME). The three isoforms are separate gene products. One isoform of NOS is a cytosolic, calcium/calmodulin-independent, inducible enzyme (iNOS). It is found in macrophages, neutrophils, vascular smooth muscle, and endothelia. The iNOS... 

---