Research Notes: Niacin

Chem Biol Interact. 2006 Oct 27.
Mitochondrial function and toxicity: role of the B vitamin family on mitochondrial energy metabolism.
Depeint F, Bruce WR, Shangari N, Mehta R, O'Brien PJ.
Department of Pharmaceutical Sciences, University of Toronto, Canada; Department of Nutritional Sciences, University of Toronto, Canada.

The B vitamins are water-soluble vitamins required as coenzymes for enzymes essential for cell function. This review focuses on their essential role in maintaining mitochondrial function and on how mitochondria are compromised by a deficiency of any B vitamin. Thiamin (B1) is essential for the oxidative decarboxylation of the multienzyme branched-chain ketoacid dehydrogenase complexes of the citric acid cycle. Riboflavin (B2) is required for the flavoenzymes of the respiratory chain, while NADH is synthesized from niacin (B3) and is required to supply protons for oxidative phosphorylation. Pantothenic acid (B5) is required for coenzyme A formation and is also essential for alpha-ketoglutarate and pyruvate dehydrogenase complexes as well as fatty acid oxidation. Biotin (B7) is the coenzyme of decarboxylases required for gluconeogenesis and fatty acid oxidation. Pyridoxal (B6), folate and cobalamin (B12) properties are reviewed elsewhere in this issue. The experimental animal and clinical evidence that vitamin B therapy alleviates B deficiency symptoms and prevents mitochondrial toxicity is also reviewed. The effectiveness of B vitamins as antioxidants preventing oxidative stress toxicity is also reviewed.

Mol Genet Metab. 2004 Apr.
Cofactor treatment improves ATP synthetic capacity in patients with oxidative phosphorylation disorders.
Marriage BJ, Clandinin MT, Macdonald IM, Glerum DM.
Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.

Marked progress has been made over the past 15 years in defining the specific biochemical defects and underlying molecular mechanisms of oxidative phosphorylation disorders, but limited information is currently available on the development and evaluation of effective treatment approaches. Metabolic therapies that have been reported to produce a positive effect include coenzyme Q(10) (ubiquinone), other antioxidants such as ascorbic acid and vitamin E, riboflavin, thiamine, niacin, vitamin K (phylloquinone and menadione), and carnitine. The goal of these therapies is to increase mitochondrial ATP production, and to slow or arrest the progression of clinical symptoms. In the present study, we demonstrate for the first time that there is a significant increase in ATP synthetic capacity in lymphocytes from patients undergoing cofactor treatment. We also examined in vitro cofactor supplementation in control lymphocytes in order to determine the effect of the individual components of the cofactor treatment on ATP synthesis. A dose-dependent increase in ATP synthesis with CoQ(10) incubation was demonstrated, which supports the proposal that CoQ(10) may have a beneficial effect in the treatment of oxidative phosphorylation (OXPHOS) disorders.

J Am Diet Assoc. 2003 Aug.
Nutritional cofactor treatment in mitochondrial disorders.
Marriage B, Clandinin MT, Glerum DM.
Department of Medical Genetics, University of Alberta, Edmonton, Alberta, Canada.

Mitochondrial disorders are degenerative diseases characterized by a decrease in the ability of mitochondria to supply cellular energy requirements. Substantial progress has been made in defining the specific biochemical defects and underlying molecular mechanisms, but limited information is available about the development and evaluation of effective treatment approaches. The goal of nutritional cofactor therapy is to increase mitochondrial adenosine 5'-triphosphate production and slow or arrest the progression of clinical symptoms. Accumulation of toxic metabolites and reduction of electron transfer activity have prompted the use of antioxidants, electron transfer mediators (which bypass the defective site), and enzyme cofactors. Metabolic therapies that have been reported to produce a positive effect include Coenzyme Q(10) (ubiquinone); other antioxidants such as ascorbic acid, vitamin E, and lipoic acid; riboflavin; thiamin; niacin; vitamin K (phylloquinone and menadione); creatine; and carnitine. A literature review of the use of these supplements in mitochondrial disorders is presented.

Ukr Biokhim Zh. 1984 Jul-Aug.
Nicotinamide nucleotides as factors of lipogenesis regulation. [Article in Russian]
Velikiĭ NN.

Data are analyzed on a regulatory effect of the redox state of NAD- and NADP-couples (the free NAD+-/NADH, NADP+/NADPH ratios) on certain enzymic links of lipogenesis. A concept is formulated on coordination of the activity of lipogenesis key enzymes by a common signal, supposedly by changes in the NAD+/NADH and NADP+/NADPH values in cytoplasm and mitochondria of the rat liver cells. High values of the NAD- and NADP-couples ratios, activation of the citrate transport from mitochondria to cytoplasm and of enzymic systems supplying lipogenesis with a substrate--acetyl-CoA, reducing equivalents (NADPH) determine the maximal lipid synthesis rate observed in adaptive hyperlipogenesis. The inhibitory action of nicotinamide on lipogenesis is realized at the level of systems providing a high metabolic pool of acetyl-CoA and dehydrogenases, producing NADPH in cytoplasm of liver cells.

Biokhimiia. 1981 Jan.
Possible mechanisms of the inhibiting effect of nicotinamide on lipogenesis in rat liver. [Article in Russian]
Mogilevich SE, Velikiĭ NN, Khalmurodov AG.

The activity of some NAD- and NADP-dependent dehydrogenases involved in generation of the reducing equivalents for lipogenesis and the activity and some kinetic parameters of ATP-citrate (pro-3S)-lyase from rat liver, i.e. the enzyme involved in the formation of CoASAc, the primary substrate of fatty acid biosynthesis, were studied. The changes in the activity of NADP-dependent dehydrogenase and ATP-citrate(pro-3S)-lyase, as well as the affinity of the latter for citrate and CoA and the rate of lipogenesis in starved rats and in rats kept on a carbohydrate-rich diet after starvation appeared to be parallel. Nicotinamide decreased the activity of all NADP-dependent dehydrogenases under study, which was especially well-pronounced after nicotinamide addition against increased lipogenesis. The affinity of ATP-citrate(pro-3S)-lyase for citrate and CoA decreased simultaneously with the decrease in the concentration of the latter. These changes can possibly induce the decrease of lipogenesis rate in rat liver after addition of nicotinamide.