Hormonal Nicotinic acid

Figure 25-7. Metabolism of adipose tissue. Hormone-sensitive lipase is activated by ACTH, TSH, glucagon, epinephrine, norepinephrine, and vasopressin and inhibited by insulin, prostaglandin E, and nicotinic acid. Details of the formation of glycerol 3-phosphate from intermediates of glycolysis are shown in Figure 24-2. (PPP, pentose phosphate pathway TG, triacylglycerol FFA, free fatty acids VLDL, very low density lipoprotein.)...

Among the active compounds were xanthurenic and 3-hydroxyanthra-nilic acids, whereas tryptophan, kynurenine, and kynurenic, anthranilic, and nicotinic acids were unable to cause deiodination. These findings support, according to the authors, the view that the deiodination of the thyroid hormone may be closely associated with its biological action. 

Schultz, Nicotinic acid inhibits adipocyte adenylate cyclase in a hormone-like manner, FEBS Lett., 1980, 335, 11-14. 

Besides being fundamental constituents of proteins they are the parent substances from which powerful hormones are derived, for example, adrenaline (epinephrine), noradrenaline (norepinephrine), thyroxine and related substances, 5-hydroxytryptamine (enteramine, serotonin), and the plant hormone indoleacetic acid. Tryptophan is also the precursor of the B vitamin nicotinic acid and hence of part of the important pyridine nucleotides. All three aromatic amino acids are potential precursors of other substances having powerful physiological activity, for example, many of the alkaloids. Errors in the metabolism of the aromatic amino acids in man can give rise to sometimes serious, but fortunately comparatively rare, disorders such as alkaptonuria and phenylketonuria. The numerous metabolic pathways involved in aromatic amino acid metabolism therefore make an important as well as an interesting study. 

In addition many stages in knowm pathways of tryptophan metabolism require further investigation, in particular, the intermediate lying between tryptophan and formylkynurenine, the hydroxylation reaction in conversion of kynureine to hydroxykynurenine, the intermediates in the conversion of hydroxyanthranilic acid to nicotinic acid, and the site of synthesis and hormonal function of 5-hydrox3dryptamine. 

Pentamidine Nicotinic acid Glucocorticoids Thyroid hormone Diazoxide... 

Patients with hypercholesterolemia do not appear to have significant alterations in bile salt synthesis rates, but patients with combined hypercholesterolemia and hypertriglyceridemia have increased synthesis rates for both cholate and chenodeoxycholate (20). Bile salt synthesis rates are not appreciably changed when nicotinic acid feeding lowers plasma cholesterol concentrations (20). Synthesis rates may also be affected by thyroid hormones. Cholic acid synthesis is decreased and half-life prolonged in hypothyroid subjects. These alterations may be corrected with thyroid hormone (21). Bile acid synthesis is increased in thyrotoxicosis (21). 

Of the hyperlipidemic drugs, clofibrate appears to decrease fecal elimination of bile acids (278-280). However, this decrease is less than the increase of the neutral steroid output, so the net elimination of cholesterol is increased (280). Thyroid hormones may occasionally, especially if associated with diarrhea, cause a marked increase in bile acid elimination (see Section VIIB), while nicotinic acid only occasionally augments fecal bile salt output (221, 281). Of the more recently developed absorbable hypolipidemic drugs, DH-581 appears to stimulate bile acid excretion at least transiently, probably by inhibiting intestinal bile acid reabsorption (282). 

The amino acid tryptophan is degraded by the higher plants to indolyl-3-acetic acid which is an important growth hormone for them, whereas bacteria usually degrade it to tryptamine, and mammals to 3-hydroxyanthranilic acid and thence to nicotinic acid which is an indispensable metabolite. 

Trigonellln 1-methylnicotinic acid, a metabolite of nicotinic acid or nicotinamide found in many plants. It is both a hormone and a storage form of nicotinic acid. It is apparently not a niacin metabolite in animals, although it is found in the urine of coffee drinkers. Green coffee beans contain relatively large (> 500 mg/kg) amounts of X roasting the beans converts T. to nicotinic acid. Coffee is a significant dietary source of niacin (see Vitamins) in South and Central America. 

The molecular manipulation of nicotinic acid designed to obtain a compound with prolonged hypoHpidemic activity has led to a substance in which the carboxyl group of nicotinic acid has been exchanged for the tetrazole moiety [70]. Such an approach had been taken previously in the plant-hormone series, where the carboxyl functions of 3-indolylacetic acid and 2,4-dichlorophenoxyacetic acids had been replaced with the tetrazole group [71]. Parenthetically, the plant-growth regulator, 2,4-dichlorophenoxyacetic acid, has also been reported to possess hypocholesterolemic activity in experimental animals [72]. 

S.2.2.2 Salvage Pathway from Nicotinamide. Although an activity that converted nicotinamide to NAD independently of nicotinic acid had been indicated for some time, the enzyme was not identified until recently (Rongvaux et al. 2002). Nicotinamide is coupled directly to phosphorybosyl pyrophosphate to form nicotinamide mononucleotide by nicotinamide phos-phoribosyltransferase, an enzyme that was previously identified as a cytokine pre-B-cell colony-enhancing factor (PBEF) and controversially claimed as an insulin-mimetic hormone visfatin (Imai 2009) (Figure 7.2). 

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