Adrenaline degradation, metabolic

Activity Like the chemically and physiologically related (R)- noradrenaline (/f)-A., as an adrenal hormone, increases the degradation of glycogen in the liver and of fat in adipose tissue as well as the oxidative metabolism in muscle. As neutrotransmitter of the adrenergic nerve system (R)-A. increases heart rate as a sympathicomimetic, constricts blood vessels of the skin, mucous membranes, and abdominal viscera, and dilates vessels of the skeletal musculature and liver. The relaxation of smooth musculature in the intestine or bronchi effected by (R)-A. leads to a reduction of peristalsis (intestinal movements) or to dilatation of the bronchi. (S)-A. is about 12 times less active than (R)-adrenaline. 

Catecholamines and their metabolites The catecholamines, adrenaline, noradrenaline, and dopamine are essential components of the central nervous system acting as neurotransmitters both within the brain and at peripheral nerves. All are synthesized in the adrenal medulla from phenylalanine or tyrosine and are metabolized by a mixture of enzymatic side chain oxidation and methylation of the hydroxy groups on the ring. If the metabolism is complete, adrenaline and noradrenaline are degraded to 4-hydroxy-3-methoxy mandelic acid (HMMA, commonly called vanillylmandelic acid - VMA), while dopamine is broken down to homovanillic acid (HVA). Urinary excretion of these metabolites and their conjugates is the major route of elimination of catecholamines from the body, although small amounts are excreted unchanged as the free catecholamines. 

The lability of benzylic bonds makes them easy targets of drug metabolism. For example, the antihypertensive metoprolol (Lopressor) works by blocking receptors for adrenaline in the heart muscles and other tissues. The first step of its degradation in the body features cytochrome enzymes (see Real Life 8-1 and Section 22-9), which hydroxylate the benzylic positions. 

---