The role of catabolism in controlling tissue concentrations of nicotinamide nucleotide coenzymes.

A previous report from this laboratory (Bender, D.A., Magboul, B.I. and Wynick, D. (1982) Brit. J. Nutr. 48, 119-127) suggested that the hydrolysis of the nicotinamide nucleotides NAD and NADP may be an important factor in controlling the tissue content of these coenzymes. Further studies presented here support this suggestion. Both nuclear poly(ADPribose) synthetase and microsomal NAD glycohydrolase showed activity towards both NAD+ and NADP+, and the two nucleotides were mutually competitive. The reduced nucleotides, NADH and NADPH, were not substrates for either enzyme. In rats that were maintained for 24 h under conditions of hypoxia (O2/N2, 1:9) there was an increase in the proportion of nicotinamide nucleotides present in the liver in the reduced form, and an increase in the total concentration of nucleotides in the liver. In rats that were maintained for 24 h under conditions of hyperoxia (O2/N2, 7:3) there was no change in either the proportion of nicotinamide nucleotides in the liver present in the reduced form or in the total tissue control of the nucleotides. There was an increase in the urinary excretion of kynurenine suggesting an increase in the oxidative metabolism of tryptophan.