Vitamin B₁₂ and the metabolism of pyridine nucleotides

Abstract

Uncoupling of oxidative phosphorylation in mitochondria from steatotic livers and in experimental thyrotoxicosis is known to be accompanied, among other changes, by a decrease in liver pyridine nucleotides which are of major importance in phosphate uptake during electron transport to molecular oxygen. The pronounced lowering of liver and its mitochondrial vitamin B₁₂ in hyperthyroidism as well as in carbon tetrachloride injury (unpublished results), together with the observed protection by the vitamin against both these stress conditions, would point to a function for the vitamin in the maintenance of tissue-levels of pyridine nucleotides. This has now been ascertained by following the effect in mice of simple vitamin B₁₂ deficiency induced by feeding on a high vegetable protein diet on the extent of incorporation in vivo of administered nicotinamide into liver pyridine nucleotides in a manner similar to that studied by Kaplan et al., and the changes in liver pyridine nucleotides, 6 and 48 hr. after carbon tetrachloride injection to adult rats as described before, without and with vitamin B₁₂ protection. Total and oxidized pyridine nucleotides were determined fluorimetrically by the procedure outlined by Dianzani.