Nicotinic Acid Mononucleotide

Nicotinic acid mononucleotide (NaMN) is the most common mononucleotide intermediate in NAD biosynthesis. It is also used in the yeast metabolic pathway. NaMN is produced by a series of enzymatic steps.

The first enzymatic step is nicotinic acid phosphoribosyltransferase (NamPRT). In this process, the phosphoribose moiety is added to the nicotinic acid. Subsequently, the side chain of the NAMN is oxidized to nicotinic acid. A second enzymatic step is the quinolinate synthetase, which catalyzes the condensation of glyceraldehyde 3-phosphate with a-iminosuccinic acid. Upon the completion of this step, the main chain of nicotinate is water-bridged to an oxygen atom.

Yeast cells use tryptophan to produce NaMN. However, the enzymatic steps involved in NaMN biosynthesis vary between species. In humans, it is encoded by NMNAT, which participates in the salvage pathway of NAD synthesis.

NMNAT is a central enzyme in cellular metabolism. It is required for the biosynthesis of NADP+ and is also involved in the salvage of nicotinic acid. NMNAT has a dual substrate specificity towards NMN and NaMN.

NMNAT has evolved from its enzymatic function to its role in complex biological processes. Recent studies have focused on the function of NMNAT as a key contributor to NAD homeostasis in pathophysiological conditions. This has allowed for the investigation of NMNAT’s evolutionary relationships and functions. Several crystal structures have been solved for NMNAT complexes with NAD.

During the course of NMNAT investigations, many different cellular processes have been uncovered. In particular, NMNAT has been implicated in the rate-limiting conversion of tiazofurin to its active form.