Related to Fig 6.

NAD⁺and PAR metabolic pathways. NAM, NMN, and NAD⁺ can be taken up by specific transporters. NAD⁺ biosynthetic pathways generate NAD⁺ from different precursors, de novo pathway employs dietary Trp or alternatively quinolinic acid (QA), NAD⁺ Salvage pathway mainly uses NAM but NMN and NR can also act as precursors. However, Preiss–Handler pathway utilizes NA. NAD⁺ is consumed by CD38 yielding NAM and ADPR or cADPR. NNMT also reduces NAD⁺ pool mediating the reaction between NAM and SAM to produce N-methylnicotinamide (1-MNA) and SAH. Finally, PARP1 synthesizes PAR by using NAD⁺ as a cofactor. PAR is degraded to ADPR mediated by different PAR hydrolases which cleave specific chemical linkages (exo- or endoglycosidically). Metabolic intermediates: NFK, NAAD, and NAMN. NAD⁺ transporter: CX43. ADPR, adenosine diphosphoribose; caDPR, cyclic ADPR; CX43, connexin 43; NA, nicotinic acid; NAAD, nicotinic acid adenine dinucleotide; NAD⁺, nicotinamide adenine dinucleotide; NAM, nicotinamide; NAMN, nicotinic acid mononucleotide; NFK, N-formylkynurenine; NMN, nicotinamide mononucleotide; NR, nicotinamide riboside; PAR, poly(ADP-ribose); SAH, S-adenosylhomocysteine; SAM, S-adenosylmethionine; Trp, tryptophan.

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