Epinephrine, biosynthesis

FIGURE 9.85 Biosynthesis of catecholstntnes. Tyrosine is used for the synthesis of various small molecules, which are used as hormones and neuiotransmitters. The nutritional biochemist mi t be especially interested in the pathway of epinephrine biosynthesis, as it requires the participation of four separate cofactors. These are fl) biopterin 2) pyridoxal phosphate 3) ascorbic acid and (4) S-adenosyl-mcthionine. 

Elastin, collagen formation Tyrosinase oxidation, skin pigment (melanin) formation Epinephrine biosynthesis... 

In view of the role played by tyrosine in melanin and epinephrine biosynthesis, the light skin pig-... 

Parahydroxyphenylpyruvic, phenylacetic, and phenyllactic acids inhibit tyrosinase, but whereas the first of these compounds is a potent inhibitor, the others are only weak inhibitors. It seems that if this inhibitory effect were important in phenylketonuria, pigment metabolism would be more apparently altered in tyrosinosis than in phenylketonuria, which seems not to be the case. However, the enzyme block might explain why small doses or dietary amounts of tyrosine have no effect on the pigmentation of patients with phenylketonuria. Only when large doses of the amino acid are administered are pigmentation and epinephrine biosynthesis restored to normal, probably because tyrosine competes with phenylalanine metabolites for melanocyte tyrosinase and dopa decarboxylase. 

Most of the drugs such as epinephrine and albuterol used to treat asthma attacks are bronchodilators—substances that expand the bronchial passages Newer drugs are designed to either inhibit the enzyme 5 lipoxygenase which acts on arachidomc acid m the first stage of leukotriene biosynthesis or to block leukotriene receptors... 

Figure 11.16 The biosynthesis of epinephrine from norepinephrine occurs by an Sjyj2 reaction with S-acfenosylmethionine.

In addition to their well known role in protein structure, amino acids also act as precursors to a number of other important biological molecules. For example, the synthesis of haem (see also Section 5.3.1), which occurs in, among other tissues, the liver begins with glycine and succinyl-CoA. The amino acid tyrosine which maybe produced in the liver from metabolism of phenylalanine is the precursor of thyroid hormones, melanin, adrenaline (epinephrine), noradrenaline (norepinephrine) and dopamine. The biosynthesis of some of these signalling molecules is described in Section 4.4. 

Biosynthesis and degradation of glycosaminoglycans biosynthesis of collagen, mineralization and demineralization of bone. Fatty acid synthesis and triglyceride storage in adipocytes promoted by insulin and triglyceride hydrolysis and fatty acid release stimulated by glucagon and adrenaline (epinephrine). 

Dopamine (3,4-dihydroxyphenyl-P-ethylamine, DA) (4.34) is a catecholamine intermediate in the biosynthesis of NE and epinephrine. There are several very important... 

Adrenal Conical Hormones. The adrenal gland is made up of two parts, the medulla and the cortex, each of which secretes characteristic hormones. The hormones of the adrenal medulla art- the catecholamines, epinephrine adrenalin and norepinephrine (noradrenalint. which are closely related chemically, dil lning only in that epinephrine has an added methyl group. See Table I. In fact, animal experiments have established a metabolic pathway lor Ihe biosynthesis of both compounds Irom Ihe ammo acid pheny lal.inine. which involves enzy malic oxidation and decarboxylation reactions It is also to he noted ihui the isomeric form of norepinephrine is most important the natural D-lonn (which incidentally, is levorntatory) has many times die uciiviiy of die synthetic isomer. Epinephrine has a pronounced action upon the circulatory system, increasing both blood... 

The most abundant alkaloid in Coryphantha macromeris, normacromerine, has been shown to originate from tyrosine (330). Tyramine and JV-methyltyramine are efficiently incorporated into normacromerine while octopamine and dopamine are poor precursors. Norepinephrine, epinephrine, normetanephrine, and meta-nephrine have all been shown to be biosynthetically incorporated into normacromerine, and they have also been shown to be naturally occurring trace intermediates in this cactus species (331, 334). Normacromerine is only slowly converted to macromerine in C. macromeris (332). The results indicate that alternative pathways to normacromerine exist precise conclusions regarding the biosynthesis of normacromerine must await further studies. 

The secretion of epinephrine by the adrenal medulla is controlled directly by nerve impulses and also by the other stress hormones, namely, corticosteroids. This is illustrated in Figure 16.11. Nerve impulses have a major stimulatory effect on tyrosine and dopamine hydroxylases, whereas glucocorticoids have a major effect on phenylethanolamine methyltransferase. Tyrosine hydroxylase is considered the rate-controlling enzyme in the biosynthesis... 

Histamine, serotonin and the catecholamines (dopamine, epinephrine and norepinephrine) are synthesized from the aromatic amino acids histidine, tryptophan and phenylalanine, respectively. The biosynthesis of catecholamines in adrenal medulla cells and catecholamine-secreting neurons can be simply summarized as follows [the enzyme catalysing the reaction and the key additional reagents are in square brackets] phenylalanine — tyrosine [via liver phenylalanine hydroxylase + tetrahydrobiopterin] —> i.-dopa (l.-dihydroxyphenylalanine) [via tyrosine hydroxylase + tetrahydrobiopterin] —> dopamine (dihydroxyphenylethylamine) [via dopa decarboxylase + pyridoxal phosphate] — norepinephrine (2-hydroxydopamine) [via dopamine [J-hydroxylasc + ascorbate] —> epinephrine (jV-methyl norepinephrine) [via phenylethanolamine jV-methyltransferase + S-adenosylmethionine]. 

Figure 6.5 Regulation of HMG-CoA reductase. HMG-CoA reductase is active in the dephospho-rylated state phosphorylation (inhibition) is catalysed by reductase kinase, an enzyme whose activity is also regulated by phosphorylation by reductase kinase kinase. Hormones such as glucagon and adrenalin (epinephrine) negatively affect cholesterol biosynthesis by increasing the activity of the inhibitor of phosphoprotein phosphatase-1, PPI-1, (by raising cAMP levels) and so reducing the activation of HMG-CoA reductase. Conversely, insulin stimulates the removal of phosphates (and lowers cAMP levels), and thereby activates HMG-CoA reductase activity. Additional regulation of HMG-CoA reductase occurs through an inhibition of synthesis of the enzyme by elevation in intracellular cholesterol levels.

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