Figure 6.

The OADHC-dependent pathways of the lysine and tryptophan catabolism, interacting with NAD metabolism. Lysine condenses with 2-oxoglutarate into saccharopine leading to 2-oxoadipate, whose oxidative decarboxylation by OADHC generates glutaryl-CoA. Glutarate is formed from glutaryl-CoA by hydrolysis or transacylation reactions⁵⁰. Tryptophan is catabolised through alternative pathways leading to either 2-oxoadipate or quinolinic acid (QA). QA is an intermediate for the de novo biosynthesis of NAD from tryptophan^115,116. In addition to its metabolic functions, NAD has signalling significance for glucose homeostasis, in particular through the Ca²⁺-mobilizing action of nicotinic acid adenine dinucleotide phosphate (NAADP), whose synthesis from NADP⁺ requires nicotinate. Dependent on cell-specific expression of the OADH-involving pathways, the OADH inhibition may downregulate saccharopine pathway and/or increase QA for biosynthesis of NAD and its signalling derivatives from tryptophan. The quantified metabolites of the presented pathways are shown in grey. Solid and dashed arrows indicate the single and more than two enzymatic reactions within a metabolic pathway, correspondingly. NA – nicotinic acid (nicotinate); NAADP – nicotinic acid adenine dinucleotide phosphate; NAM – nicotinamide; NAMN – nicotinic acid mononucleotide; QA – quinolinic acid.