Niacin nucleotide synthesis and glycolytic activity in erythrocytes of patients suffering from pellagra

Abstract

Erythrocytes of subjects with pellagra exhibit impaired synthesis of NAD from nicotinic acid in vitro. A detailed time course study of in vitro incorporation of 14C-nicotinic acid into NAD and its intermediates namely nicotinic acid mononucleotide (NaMN), nicotinic acid adenine dinucleotide (NaAD) was made in erythrocytes of patients with pellagra and normal subjects. The incorporation of 14C-nicotinic acid into the total nucleotides (NAD + NaAD + NaMN) was significantly reduced in the erythrocytes of pellagrins at 6 and 21 hours. Relatively more radioactivity was found in NaMN during these periods indicating thereby, that the conversion of NaMN to NaAd may be defective in pellagra. This was confirmed by label chasing experiment, in which NaMN of the intact cells was prelabeled with 14C-nicotinic acid, and its further conversion to NaAD was followed in vitro. The activity of nicotinate phosphoribosyl transferase, was normal in the erythrocytes of pellagrins. Concentration of ATP and glycolytic activity of the erythrocytes were investigated under conditions for NAD synthesis. A significant reduction in the basal levels of ATP was observed in pellagrins. As compared to normals, the rate of glycolytic activity, and the levels of ATP during NAD synthesis, was significantly lower in the erythrocytes of pellagrins. From the data obtained, it was concluded that the fall in ATP concentration found in the erythrocytes of pellagrins may not be the limiting factor for the optimal synthesis of NAD. Instead, the defect in lowered NAD synthesis, may be due to reduced activity of the enzyme NaMN adenyl transferase, which converts NaMN to NaAD.