Seminar, 04. February 2019, Ines Heiland

Monday, 04. February 2019, 14.15 p.m. 

Ernst-Abbe-Platz 2, seminar room 3423

Understanding the evolution of NAD metabolism and its consequences for human physiology

Prof. Dr. Ines Heiland
(Dept. of Arctic and Marine Biology Faculty of Bioscience, Fisheries and Economics; UiT The Arctic University of Norway; Norway)

NAD provides an important link between metabolism and signal transduction and has emerged as central hub between bioenergetics and all major cellular events. NAD-dependent signalling, e.g. by sirtuins and PARPs, consumes considerable amounts of NAD and releases nicotinamide (Nam). To maintain physiological functions, NAD consumption and biosynthesis need to be carefully balanced. In eukaryotes, two diff erent Nam salvage pathways exist. While in lower organisms the initial deamidation of Nam is prevalent, in animals the direct conversion of Nam to the mononucleotide by Nam phosphoribosyltransferase (NamPRT) dominates and eventually remains as the single Nam recycling route in vertebrates.

Using comprehensive phylogenetic analyses combined with mathematical modelling and experimental verification, we can explain the evolutionary development of the pathways and identify the evolutionary events that were essential to develop the diverse NAD-dependent signalling present in vertebrates. Our results reveal co-evolution and unexpected kinetic interplay between enzymes of the pathway that have implications for therapeutic strategies of NAD supplementation and cancer treatments.