Nicotinic acid mononucleotide pyrophosphorylase

The third hypothesis has found some support from the work of Pardee [96] and his collaborators. These investigators studied in Escherichia coli the activity of nicotinic acid, mononucleotide pyrophosphorylase, nicotinic acid dinucleotide pyrophosphorylase, NAD... 

Nicotinic acid mononucleotide reacts with ATP in the presence of nicotinic acid adenine dinucleotide pyrophosphorylase, a magnesium-dependent enzyme, to yield the deamido derivative of NAD (see Fig. 4-11). Deamido NAD, in the presence of ATP, glutamine, Mg, K", and an NAD synthetase, is converted to NAD. In this reaction, the amino group of glutamine is transferred to the carboxyl group of the nicotinic acid moiety of deamido NAD. Yet the nicotinamide moiety of NAD synthetase is found in liver supernatant and, as may be expected, it is inhibited by azaserine. 

The breakdown pathways for NAD and NADP were discussed in the section on electron transport. Studies in Pardee s laboratory have shed some new light on the control of NAD synthesis in E. coli (see Fig. 4-10). Pardee was able to demonstrate that in the sequence of reactions, the NAD mononucleotide pyrophosphorylase reaction is the rate-limiting step. The levels of pyrophosphorylase are low in the wild type of E. coli, but they are even lower in mutants requiring nicotinic acid for growth when the bacteria... 

A considerable advance in elaborating the pathway of pyridine coenzyme synthesis resulted from the contributions of Preiss and Handler (118, 1B6-1B8). Before discussing the experiments of these investigators, it may be of value to review some of the earlier work on the metabolism of nicotinic acid and nicotinamide in erythrocytes. It has been known for some time that nicotinic acid taken orally results in a significant increase in the pyridine nucleotide content of human red blood cells (1B9, ISO). When equal concentrations of nicotinamide were given under identical conditions, there was no effect on the erythrocyte DPN level. Isolated erythrocytes have also been found to show a rise in DPN when incubated with nicotinic acid and not with nicotinamide. However, incubation with nicotinamide leads to a marked accumulation of nicotinamide mononucleotide (ISl). In this connection, it is of importance to point out that the level of the DPN pyrophosphorylase is extremely low in the red blood cell (ISB). 

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