Nicotinic Acid and Its Derivatives

Observation of the inactivation of cozymase by yeast preparations was contemporary with the discovery, at the beginning of the present century, CH N 

Several observations on the behavior of influenza bacilli toward V factor, before chemical characterization of the factor, had suggested certain connections with the metabolism of the bacteria (see 106) though only in very general terms. More specific was Pittman s (95) observation of the lesser need by H. influenzae for V factor when culture fluids (containing excess of other growth essentials) were given good contact with air. 

A prominent feature of the Lwoffs studies was the simple manner in which further reactions of the coenzymcs were connected with their functioning. In doing this, much depended on the different properties of coenzymes I and II, which in the observations described in the previous paragraphs had not behaved differently. 

Thus deficiencies in each type of organism were made good by either coenzyme. In inducing deficiencies, glucose and hexose monophosphate behaved similarly, but differently from pyruvate, fumarate, malate, ethanol, some amino acids, and the peptone of the basal medium. 

Knowing that the hexose monophosphate system of other organisms required coenzyme II, it was assumed that the cells unable to dehydrogen- 

---

Nicotinyl alcohol (3-pyridinylcarbinol, 3-pyridinemethanol) (27) has use as an antilipemic and peripheral vasodilator. It is available from either the reductions of nicotinic acid esters or preferably, the reduction of the nitrile to the amine followed by dia2otation and nucleophilic displacement. It is frequently adininistered in the form of the tartrate (Eig. 7). Nicotinic acid is frequently used as a salt in conjunction with basic dmgs such as the peripheral vasodilator xanthinol niacinate (28). Nicotinic acid and its derivatives have widespread use as antihyperlipidemic agents and peripheral vasodilators (1). 

Walldius G, Wahlber G. Nicotinic acid and its derivates. In Lipoproteins in Health and Disease (Betteridge DJ, Illingworth DR, Shepherd J, Eds.). London Arnold 1999, 1181-1197. 

Nicotinic acid and its derivatives (pyridylcarbinol, xanthinol nicotinate, acipimox) activate endothelial lipoprotein lipase and thereby lower triglyceride levels. At the start of therapy, a prostaglandin-mediated vasodilation occurs (flushing and hypotension) that can be prevented by low doses of acetyl-salicylic acid. 

FIGURE 13-17 Structures of niacin (nicotinic acid) and its derivative nicotinamide. The biosynthetic precursor of these compounds is tryptophan. In the laboratory, nicotinic acid was first produced by oxidation of the natural product nicotine—thus the name. Both nicotinic acid and nicotinamide cure pellagra, but nicotine (from cigarettes or elsewhere) has no curative activity. 

Walldius G, Wahlberg G (1985) Effects of nicotinic acid and its derivatives on lipid metabolism and other metabolic factors related to atherosclerosis. Adv Exp Med Biol 183 281-293... 

J. P. I ELBER and V. Buber, Effect of nicotinic acid derivative on glucose levels and glucose tolerance in animal and man. In K. F. Gey and L.A. Carlson (eds) Metabolic Effects of Nicotinic Acid and its Derivatives, Huber, Berne, 1970, pp. 695-710. 

The nicotinic acid pathway potentially gives rise to a number of excretion products, largely due to side reactions, such as anthranilic acid, kynurenic acid, and xanthurenic acid, but normally these are excreted in, at most, small amounts. Presumably, therefore, the greater part of ingested tiyp-tophan should give nicotinic acid or simple derivatives. But normal excretion of nicotinic acid and its derivatives is in any case low, and when... 

Again this year there have been a number of reports which describe reactions of heteroaromatic compounds in alcoholic solvents many of these reactions are dependent upon the acidity of the media and the structure of the alcohol. The reactivity of nicotinic acid and its derivatives in such systems demonstrates this... 

Nicotinic acid and its derivatives are stable to oxidation by heat, light, acid or alkali and this means that extraction into solvent systems compatible with HPLC is relatively easy by comparison with other vitamins. Biological extracts are readily prepared by deproteini-sation with acetone followed by extraction with dilute hydrochloric acid alternatively, ethyl acetate in combination with hydrochloric acid may be used to extract samples. The most popular HPLC mode for the separation of nicotinic acid is reversed phase ion-pair chromatography. For example, using a fiBondapak Cjg column with a mobile phase of water-methanol (9 1) plus 0.05 M tetrabutylam-monium phosphate as the ion-pair reagent, nicotinamide-A-oxide, 2-hydroxypyridine-5-carboxylic acid, nicotinamide, nicotinic acid and nicotinuric acid were consecutively eluted (Hengen et al., 1978). 

Walldius G, Wahlberg G. Nicotinic acid and its derivatives In Lipoproteins in Health and Disease. Editors DJ Betteridge, DR Illingworth, J Shepherd Arnold, London. 1999. pp. 1181-1198. 

Also called niacin refers to both nicotinic acid and its derivative nicotinamide (also called niacinamide). Both occnr widely in natnre, with nicotinic acid being more prevalent in plants, and nicotinamide in animals. Yeast, liver, poultry, lean meats, nuts and legumes contribute most of niacin in food. Milk and leafy green vegetables contribute lesser amounts. Niacin belongs to the group of B vitamins. 

Rates of Micwobial Reaction with Nicotinic Acid and Its Derivatives... 

Recent literature does not point to side effects of nicotinic acid and its derivatives other than those which were reviewed in SED VIII (p. 936). The field has been reviewed by Parsons (26 ), who has stressed the need for a major study to determine the long-term effects of nicotinic acid as compared with other lipid-reducing agents. One of the few long-term studies recently reported, that of Zbllner et al. (27 ) is a follow-up on 37 patients who had been treated for hypercholesterolaemia with nicotinyl alcohol for between 6 and 8 years. Those who had taken more than 0.9 g daily still had a lower serum cholesterol than at the beginning of treatment, and there was no evidence of long-term adverse effects. 

---