Nicotinic Deficiency

Nicotinic acid (niacin) is a precursor of nicotinamide adenine dinucleotide (NAD) which plays a central role in metabolism as a coenzyme. It can be synthesized from tryptophan. Tryptophan and nicotinate deficiency lead to pellagra, which is characterized by diarrhea, dermatitis, and dementia. Maize-rich diets... 

Pella r, Nia.cin Deficiency. It was 220 years after the first description of pellagra that nicotinic acid was discovered to be the cure for black tongue in dogs (14), a condition suggested by a veterinarian in North Carolina to be similar to human pellagra (15). 

Attempts to isolate GTF from brewer s yeast have resulted in production of very active concentrates, but the substance is too labile to be obtained in the soHd state (136). However, it has been shown that GTF is a Cr(III) complex containing two coordinated nicotinate radicals and other amino acid anions (146). Active preparations containing similar complexes have been synthesi2ed (147). Chromium deficiency may also lead to atherosclerosis and peripheral neuropathy. 

NADP can be converted to nicotinic acid adenine dinucleotide phosphate (NAADP), which has distinct functions in the regulation of intracellular calcium stores. The studies of these new roles of NAD(P) in metabolism are in their early stages, but they might soon help to better understand and explain the symptoms of niacin deficiency ( pellagra) [1]. 

Specific concomitant medications or consumptions (check specific statin package insert for warnings) fibrates (especially gemfibrozil, but other fibrates too), nicotinic acid (rarely), cyclosporine, azole antifungals such as itraconazole and ketoconazole, macrolide antibiotics such as erythromycin and clarithromycin, protease inhibitors used to treat Acquired Immune Deficiency Syndrome, nefazodone (antidepressant), verapamil, amiodarone, large quantities of grapefruit juice (usually more than 1 quart per day), and alcohol abuse (independently predisposes to myopathy)... 

Among mammals, symptoms of nicotinic acid deficiency have been... 

Epileptiform fits associated with degenerative changes in the myelin sheath of peripheral nerves and spinal cord occur in B6-deficient animals. Lesions in the arteries, resembling those of human atherosclerosis, have been observed in Be-deficient monkeys. Recently, a state of Be deficiency in human infants, characterized by loss of ability to convert tryptophan to nicotinic acid, by impaired growth, convulsions, and hypochromic anemia, has been described, following omission of vitamin B6 from the diet. 

Nicotinic acid, when given at the rate of several hundred milligrams a day, has pharmacological effects of which cerebral vasodilation is one. Nicotinamide does not have this effect, and hence the pharmacological effects of nicotinic acid probably do not involve simple replacement of a deficiency in an enzyme system. The fact that nicotinic acid itself in pharmacological doses appears to be of Implications for Advance in Psychiatry... 

Sasaki FI, Yanai M, Meguro K, Sekizawa K, Ikarashi Y, Maruyama Y, Yamamoto M, Matsuzaki Y, Takishima T. (1991). Nicotine improves cognitive disturbance in rodents fed with a choline-deficient diet. Pharmacol Biochem Behav. 138(4) 921-25. 

Orr-Urtreger A, Goldner FM, Saeki M, Lorenzo 1, Goldberg L, deBiasis M, Dani JA, Patrick JW, Beaudet AL (1997) Mice deficient in the a7 neuronal nicotinic acetylchohne receptor lack a-bungarotoxin binding sites and hippocampal fast nicotinic currents. J Neurosci 17 9165-9171... 

Benowitz ML, Jacob P 3rd, Fong I, Gupta S (1994) Nicotine metabolic profile in man comparison of cigarette smoking and transdermal nicotine. J Pharmacol Exp Ther 268 296-303 Benowitz NL, Perez-Stable EJ, Eong 1, Modin G, Herrera B, Jacob P 3rd (1999) Ethnic differences in N-glucuronidation of nicotine and cotinine. J Pharmacol Exp Ther 291 1196-1203 Benowitz NL, Griffin C, Tyndale R (2001) Deficient C-oxidation of nicotine continued. Chn Pharmacol Ther 70 567... 

Niacin, which refers to nicotinic acid and nicotinamide, is the metabolic precursor to three nicotinamide coenzymes. These are essential for the activity of a large number of enzymes catalyzing redox reactions. Pellagra is a niacin deficiency disease. 

Oxidation of nicotine with chromic acid led to the isolation of pyridine-3-carboxylic acid, which was given the trivial name nicotinic acid. We now find that nicotinic acid derivatives, especially nicotinamide, are biochemically important. Nicotinic acid (niacin) is termed vitamin B3, though nicotinamide is also included under the umbrella term vitamin B3 and is the preferred material for dietary supplements. It is common practice to enrich many foodstuffs, including bread, flour, corn, and rice products. Deficiency in nicotinamide leads to pellagra, which manifests itself in diarrhoea, dermatitis, and dementia. 

Nicotinate and nicotinamide, together referred to as niacin, are required for biosynthesis of the coenzymes nicotinamide adenine dinucleotide (NAD"") and nicotinamide adenine dinucleotide phosphate (NADP" ). These both serve in energy and nutrient metabolism as carriers of hydride ions (see pp. 32, 104). The animal organism is able to convert tryptophan into nicotinate, but only with a poor yield. Vitamin deficiency therefore only occurs when nicotinate, nicotinamide, and tryptophan are all simultaneously are lacking in the diet. It manifests in the form of skin damage (pellagra), digestive disturbances, and depression. 

Develop a model of the burning of a cigarette. The primary reactions can be regarded as the burning of sohd carbon to CO2 in excess O2 and to CO if oxygen deficient. In the absence of O2 the tobacco pyrolyzes to carbon with the vaporization of tars and nicotine, which for unexplained reasons some people like to inhale into their lungs. 

Drug-induced niacin deficiency has resulted from the use of isonicotinic acid hydrazide, which interferes with the conversion of niacin from tryptophan. Administration of ethanol or the antimetabolites 6-mercaptop-urine and 5-fluorouracil also may lead to niacin deficiency. The uricosuric effects of sulfinpyrazone and probenecid may be inhibited by nicotinic acid. 

Adler LE, Hoffer LD, Griffith J, et al Normalization of the deficient auditory sensory gating in the relatives of schizophrenics by nicotine. Biol Psychiatry 32 607-616,... 

Nicotine forms a number of metabolites in the body, mainly in the liver. Approximate 75% of nicotine is oxidized to cotinine, which is the primary nicotine metabolite. Cotinine can be measured in the blood, urine, and saliva and this is used as a measure of nicotine exposure in tobacco users and in those exposed to secondhand smoke. The oxidation of nicotine also produces nicotinic acid. Nicotinic acid is vitamin B3 and has the common name niacin. Niacin deficiency results in a disease called pellagra, which is found in certain malnourished populations. Pellagras symptoms include dermatitis, diarrhea, sensitivity to light, and dementia. 

Niacin (nicotinic acid, nicotinamide) has the active forms NAD and NADPH. It functions in electron transfer. A deficiency of niacin causes pellagra, which is characterized by der matitis, diarrhea, and dementia. There is no known toxicity for this vitamin. High doses of niacin are used to treat hyperlipidemia. 

Two vitamins, nicotinamide and pyridoxine (vitamin B6), are pyridine derivatives. Nicotinamide participates in two coenzymes, coenzyme I (65 R = H) which is known variously as nicotinamide adenine dinucleotide (NAD) or diphosphopyridine nucleotide (DPN), and coenzyme II (65 R = P03H2) also called triphosphopyridine nucleotide (TPN) or nicotinamide adenine dinucleotide phosphate (NADP). These are involved in many oxidation-reduction processes, the quaternized pyridine system acting as a hydrogen acceptor and hydrogen donor. Deficiency of nicotinamide causes pellagra, a disease associated with an inadequately supplemented maize diet. Nicotinic acid (niacin) and its amide are... 

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