Human Biochemistry, Volume 2 - Murray R. 1993

Biochemistry of Intra- and Intercellular Communication
Adrenal Medullary Hormones
Catecholamine Metabolism

Only a very small fraction of adrenaline (less than 5%) is excreted in the urine. Catecholamines are rapidly metabolized by catechol-O-methyltransferase and monoamine oxidase to yield inactive O-methylated and deaminated products (Fig. 49.3). Most catecholamines serve as substrates for both Enzymes, and these reactions can occur in any sequence.

Class="center">

Fig. 49.2. Pathway of catecholamine Biosynthesis. TH — Tyrosine hydroxylase; DC — DOPA decarboxylase; PNMT — phenylethanolamine N-methyltransferase; DBH — dopamine-β-hydroxylase; ATP — adenosine triphosphate. Catecholamine biosynthesis occurs in the Cytoplasm and various granules of the adrenal medullary Cells. Some granules contain adrenaline (A), others contain noradrenaline (NA), and some contain both Hormones. Upon stimulation, the entire granule contents are released into the extracellular fluid (ECF).

Catechol-O-methyltransferase (COMT) is a cytosolic enzyme found in many Tissues. It catalyzes The transfer of a methyl group, typically to the third position (meta-position) of the benzene ring of various catecholamines. The reaction requires a divalent cation and S-adenosylmethionine as a methyl group donor. Depending on the substrate used, this reaction yields homovanillic acid, normetanephrine, and metanephrine.

Monoamine oxidase (MAO) is an oxidoreductase that deaminates monoamines. It is found in numerous tissues, with the highest concentrations in the Liver, Stomach, Kidneys, and intestine. At least two MAO Isoenzymes have been characterized: MAO-A in neural tissue, which deaminates serotonin, adrenaline, and noradrenaline, and MAO-B in other (non-neural) tissues, which is most active toward 2-phenylethylamine and benzylamine. Dopamine and tyramine are metabolized by both forms. The relationship between Affective Disorders and changes in The activity of these isoenzymes is currently an area of active investigation. MAO inhibitors have found clinical application in the Treatment of Hypertension and depression; however, their utility is limited by their propensity to cause hazardous adverse interactions with dietary and pharmacological sympathomimetic amines.

The O-methoxylated derivatives undergo further modification through conjugation with glucuronic or sulfuric acid.

Catecholamines give rise to a multitude of metabolites. Two classes of these metabolites are used in clinical Diagnostics because they are excreted in the urine in readily measurable quantities. Metanephrines represent the methoxy derivatives of adrenaline and noradrenaline, whereas the O-methylated deaminated product of both is 3-methoxy-4-hydroxymandelic acid (also known as vanillylmandelic acid, VMA) (Fig. 49.3). In pheochromocytoma, urinary concentrations of metanephrines or VMA are elevated in more than 95% of patients. Diagnostic tests based on the measurement of these metabolites exhibit high diagnostic accuracy, especially when used in combination with assays for urinary or plasma catecholamines.