NAD+ Degrading Enzymes, Evidence for Roles During Infection
Arnold Tan, Craig Doig
Abstract
Declines in cellular nicotinamide adenine dinucleotide (NAD) contribute to metabolic dysfunction, increase susceptibility to disease, and occur as a result of pathogenic infection. The enzymatic cleavage of NAD + transfers ADP-ribose (ADPr) to substrate proteins generating mono-ADP-ribose (MAR), poly-ADP-ribose (PAR) or O-acetyl-ADP-ribose (OAADPr). These important post-translational modifications have roles in both immune response activation and the advancement of infection. In particular, emergent data show viral infection stimulates activation of poly (ADP-ribose) polymerase (PARP) mediated NAD + depletion and stimulates hydrolysis of existing ADP-ribosylation modifications. These studies are important for us to better understand the value of NAD + maintenance upon the biology of infection. This review focuses specifically upon the NAD + utilising enzymes, discusses existing knowledge surrounding their roles in infection, their NAD + depletion capability and their influence within pathogenic infection.