Phenylethanolamine-N-methyltransferase PNMT

In cells that synthesize epinephrine, the final step in the pathway is catalyzed by the enzyme phenylethanolamine /V-methyltransferase. This enzyme is found in a small group of neurons in the brainstem that use epinephrine as their neurotransmitter and in the adrenal medullary cells, for which epinephrine is the primary hormone secreted. Phenylethanolamine N-methyltransferase (PNMT) transfers a methyl group from S-adenosylmethionine to the nitrogen of norepinephrine, forming a secondary amine [5]. The coding sequence of bovine PNMT is contained in a... 

Levels of phenylethanolamine-N-methyltransferase (PNMT) have been found to be significantly raised in discrete brain stem regions in both SHR and DOCA-salt hypertensive rats.33 Administration of SKF 7698 (7), a PNMT inhibitor, normalized pressure in DOCA rats. The possibility that the effect was due to the adrenolytic action of (7) was not excluded. The best of a new series of PNMT inhibitors with much reduced a-blocking properties is SKF 6 139 (8).3 ... 

Norepinephrine diifuses into the cytosol, where it is converted to epinephrine by methylation of its amino group. This reaction, in which the methyl group is donated by S-adenosylmethionine, is catalyzed by S-adenosyl-L-methionine phenylethanolamine-N-methyltransferase (PNMT). Epinephrine enters the granules and remains there until it is released. 

As described, the secretion of epinephrine in response to stress, trauma, extreme exercise, or hypoglycemia causes a rapid mobilization of energy stores, that is, glucose from the liver and fatty acids from adipose tissue. The reaction in which NE is methylated to form E is mediated by the enzyme phenylethanolamine-N-methyltransferase (PNMT). Although the enzyme occurs predominantly in the chromaffin cells of the adrenal medulla, it is also... 

Transferases are enzymes that catalyze the transfer of functional groups from one molecule to another. For example, a transaminase catalyzes the transfer of an amino functional group, and a kinase catalyzes the transfer of a phosphate group. Kinases play a major role in energy-harvesting processes involving ATP. In the adrenal glands, norepinephrine is converted to epinephrine by the enzyme phenylethanolamine-N-methyltransferase (PNMT), a transmethylase. 

Nicotinamide N-methyltransferase (NNMT) methylates serotonin, tryptophan, and pyridine-containing compounds such as nicotinamide and nicotine. Phenylethanolamine N-methyltransferase (PNMT)... 

Figure 42-10. Biosynthesis of catecholamines. (PNMT, phenylethanolamine-N-methyltransferase.)...

Figure 1. Biosynthetic pathways for biogenic amines. In Drosophila and vertebrates decarboxylation of DOPA and 5-hydroxy-tryptophan is catalyzed by the same enzyme, DDC. In vertebrates this enzyme is called amino acid decarboxylase (AADC). Only vertebrates further metabolize dopamine to norepinephrine and epinephrine. TH, tryosine hydroxylase DDC, DOPA decarboxylase DBH, dopamine b-hydroxylase PNMT, phenylethanolamine N-methyltransferase. Tryp-OH tryptophan hydroxylase.

Steps in the formation of classical neurotransmitters. AADC, amino acid decarboxylase AChE, acetylcholinesterase CAT, choline acetyltransferase COMT, catechol-O-methyltransfeiase DBH, dopamine P-hydroxylase DA, dopamine DOPA, dibydroxyphenylalanine GABA-T, GABA transaminase GAD, glutamic acid decarboxylase HD, histidine decarboxylase 5-HTP, 5-hydroxytrytophan MAO, monoamine oxidase PNMT, phenylethanolamine N-methyltransferase TH, tyrosine hydroxylase TPH, tryptophan hydroxylase. 

Figure 1. Pathway for the production of phenolamine from tyrosine. The reactions are catalyzed by the following enzymes DD, DOPA decarboxylase DBH, dopamine 8-hydroxylase PNMT, phenylethanolamine-N-methyltransferase. Data from reference 12.

Monoamine oxidase is a flavoprotein that catalyzes the oxidative deamination of amines to form the corresponding aldehydes. 02 is the electron acceptor, and NH3 and H202 are the other products. (PNMT = phenylethanolamine-N-methyltransferase.)... 

Figure 12.4. Pathways in the metabolism of L-dopa (1) and its major decarboxylated product dopamine (2). Major (heavy arrows) and minor (light arrows) reactions are indicated. AD, aldehyde dehydrogenase AAD, aromatic L-amino acid decarboxylase COMT, catechol-O-methyltransferase DH, dopamine jS-hydroxylase MAO, monoamine oxidase PNMT, phenylethanolamine-N-methyl-transferase.

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