Enzymology of mammalian NAD metabolism in health and disease

Giulio Magni, Giuseppe Orsomando, Nadia Raffelli, Silverio Ruggieri

Istituto di Biotecnologie Biochimiche, Università Politecnica delle Marche, Via Ranieri 69, 60131 Ancona, Italy

FIGURES

Figure 1. Mammalian NAD biosynthesis. The box summarizes major physiological and pathological processes implicating NAD metabolism. The asterisk, indicating the route from NAD/NADP to nicotinamide, includes the reactions catalyzed by SIRTs , PARPs and other ADP-ribosyltransferases. Na and N indicate nicotinic acid and nicotinamide, respectively. ACMS and AMS refer to 2-amino 3-carboxymuconate 6-semialdehyde and 2-aminomuconate 6-semialdehyde, respectively.

Figure 2. Schematic overview of tryptophan catabolism through the "kynurenine pathway". Digits indicate the intermediates of the pathway: tryptophan (1); L-kynurenine (2); kynrenic acid (3); 3-hydroxykynurenine (4); 3-hydroxyanthranilate (5); 2-amino 3-carboxymuconate 6-semialdehyde (ACMS) (6); 2-aminomuconate 6-semialdehyde (AMS) (7); picolinate (8); quinolinate (9). Italicized fonts refer to the enzymes: tryptophan/indoleamine 2,3-dioxygenase (a); kynurenine formamidase (b); kynurenine aminotransferase (c); kynurenine 3-hydroxylase (d); kynureninase (e); 3-hydroxyanthranilate 3,4-dioxygenase (f); 2-amino 3-carboxymuconate 6-semialdehyde decarboxylase (g). Dotted arrows marked with asterisks indicate the two non-enzymatic reactions of the pathway leading to quinolinate or picolinate formation.

Figure 3. 2-Amino 3-carboxymuconate 6-semialdehyde decarboxylase-catalyzed reaction.

Figure 4. Quinolinate phosphoribosyltransferase-catalyzed reaction.

Figure 5. NMN adenylyltransferase-catalyzed reaction.

Figure 6. NAD synthetase-catalyzed reaction.

Figure 7. NAD kinase-catalyzed reaction.

Figure 8. Nicotinate phosophoribosyltransferase-catalyzed reaction.

Figure 9. Nicotinamide phosphoribosyltransferase-catalyzed reaction.