Niacin activities, increased

Hinshaw et al. (1999) have shown that activation of PARP may be linked to ATP-dependent changes in microfilament architecture in cells. The PARP activation hypothesis is thus well supported although Lin et al. (1994) failed to find a link between depletion of NAD+ and cell damage in rat keratinocyte cultures. These authors used nicotinamide to prevent a fall in NAD+ levels but found that this did not prevent the decline in DNA content used as an index of cytotoxicity. This is a particularly important finding as Papirmeister et al. (1985) have also used nicotinamide and niacin to increase levels of NAD+ in cells. They noted, however, that nicotinamide was an inhibitor of PARP but that niacin was not. They argued that niacin would allow DNA repair without concomitant depletion of NAD+. They... 

Quinolinic Acid. Assignment of a place to quinolinic acid as an intermediate in nicotinic acid formation is based on the evidence that its excretion into the urine is increased by injection of tryptophan or of 3-hydroxyanthranilic acid. Quinolinic acid isolated from the urine on treatment with acid gives rise to a substance having niacin activity for L. arabinosus. ... 

Drug interactions InsuUn requirements may be increased by medications with hyperglycemic activity such as corticosteroids, isoniazid, certain lipid-lowering drugs (e.g., niacin), estrogens, oral contraceptives, phenothiazines, and thyroid... 

Correct answer = D. Clofibrate and gemfibrozil Increase the activity of lipoprotein lipase, thereby increasing the removal of VLDL from plasma. Niacin inhibits lipolysis in adipose tissue and thus eliminates the building blocks needed by the liver to produce triacylglycerol and there-... 

Low HDL cholesterol is a strong independent risk predictor of CHD. ATP III redefined low HDL cholesterol as <40 mg/dL but specified no goal for HDL cholesterol raising. In low HDL, the primary target remains LDL, but treatment emphasis shifts to weight reduction, increased physical activity, smoking cessation, and to fibrates and niacin if drug therapy is required. 

The best-established function of poly(ADP-ribose) polymerase is in repair of damaged DNA it is activated by DNA strand breaks, and acts to clear histones and other nucleoproteins away from the DNA to permit access of the DNA repair enzymes. Both in vitro and in experimental animals, niacin deficiency leads to increased genomic instability, as the ability to repair damaged DNA is impaired, and may increase tumor risk. There is little information about genomic instability and cancer risk in human niacin deficiency (ffageman and Stiemm, 200f). 

A number of inborn errors of metabolism of the tryptophan oxidative pathway (see Figure 8.4) have been reported, aU of which result in the development of pellagra that responds to high doses of niacin. These conditions include vitamin Be-responsive xanthurenic aciduria, caused by a defect of kynureni-nase (Section 9.4.3) hydroxykynureninuria, apparentiy caused by a defect of kynureninase tryptophanuria, apparentiy caused by tryptophan dioxygenase deficiency a hereditary pellagra-like condition, apparentiy caused by an increase in activity of picoUnate carboxylase and Hartnup disease. 

More than two decades ago I began my search for ways to lower my own cholesterol levels and prevent an early death from heart disease. Certainly, the essential foundation of sueh a program had to include increased physical activity and a heart-healthy diet. But knowing that other factors entered into the cholesterol picture—notably, that the body makes 80 percent of all the cholesterol in the bloodstream—I realized that I needed something more than diet and exercise. My search led me to the soluble fibers in oat bran and other foods that actually flush out cholesterol and the vitamin niacin to stop the body s excessive production of it. Since that time, I ve found additional natural approaches to lowering cholesterol, including the plant sterols known as phytosterols, red yeast rice, and pantethine. 

Nicotinamide, but not niacin, is taken up into the brain by an active uptake process (31) and is converted into NAD (Fig. 11.9). Niacin released in the brain from catabolic processes is converted into nicotinamide as shown. Nicotinamide can increase brain levels of NAD by 50% or more (32). By increasing brain NAD levels, nicotinamide prevents ATP depletion (9) and protects cellular DNA (32). Therefore, nicotinamide maintains cellular energetics in the presence of oxidative stress. 

Because flavin coenzymes are widely distributed in intermediary metabolism, the consequences of deficiency maybe widespread. Because riboflavin coenzymes are involved in the metabohsm of folic acid, pyridoxine, vitamin K, and niacin, deficiency will affect enzyme systems other than those requiring flavin coenzymes. With increasing riboflavin deficiency, tissue concentrations of FMN and FAD fall, as does flavokinase activity, thus further decreasing FMN concentrations. FMN concentrations are decreased proportionally more than FAD concentrations. Decreases in the activities of enzymes requiring FMN generally follow the fall in tissue concentrations, whereas the FAD-dependent enzymes are more variably affected. ... 

Other evidence consistent with this is that in bipolar disorder there is excessive flushing in response to niacin (Hudson et al., 1997 Ward et al., 1998). This is consistent with overactivity of CPLA2 but without any associated abnormality in FACE such as seems to occur in schizophrenia and that reduces the availability of AA for niacin-mediated signal transduction. However, there is no evidence from the enzyme-linked immunosorbent assay (ELISA) assay that, in bipolar disorder, there is any elevation of CPLA2 protein levels in red cells (MacDonald et al., 2000). If CPLA2 is elevated in bipolar disorder, it seems more likely to be related to increased activity of the enzyme, possibly as a result of an activating factor such as one of the S-100 group of protein, rather than to an increased amount of enzyme. 

The occurrence of mitochondrial damage and oxidative stress has been repeatedly found in the chnical setting and in e q)erimental models of Parkinson s disease [52]. Treatment of Parkinson s disease patients with vitamin E has not provided definite positive results however, a combination of antioxidants [46, 53], including vitamins such as niacin and riboflavin, is strongly recommended [46,54]. Treatment of patients with Alzheimer s disease with vitamin E (2000 mg day ) has been reported to improve the patients event-free-sur-vival (cognitive activity) [55]. It has also been claimed that an increased intake of vitamin E lowers the risk of Alzheimer s disease [56,57]. 

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