# Is NAD+ a Substrate or a Product? What Enzyme Records Show Updated 2026-11-06. NAD+ is both a substrate and a product, depending on the reaction. A substrate is a molecule an enzyme uses up. A product is a molecule an enzyme makes. Redox enzymes, sirtuins, PARPs and CD38 use NAD+ as a substrate. NMNAT enzymes, NAD synthase and the NADH-oxidising enzyme complex I make NAD+ as a product (ExPASy ENZYME; Rhea; Covarrubias et al., 2021). | | | | --- | --- | | Substrate: lactate dehydrogenase | (S)-lactate + NAD+ = pyruvate + NADH + H+. EC 1.1.1.27 ([ExPASy ENZYME](https://enzyme.expasy.org/EC/1.1.1.27); [Rhea 23444](https://www.rhea-db.org/rhea/23444)). | | Substrate: sirtuin deacetylase | Protein acetyl-lysine + NAD+ + H2O gives 2'-O-acetyl-ADP-ribose + nicotinamide + protein lysine. EC 2.3.1.286 ([ExPASy ENZYME](https://enzyme.expasy.org/EC/2.3.1.286); [Rhea 43636](https://www.rhea-db.org/rhea/43636)). | | Substrate: PARP | NAD+ + an ADP-ribose chain on an acceptor gives nicotinamide + a longer chain. EC 2.4.2.30 ([ExPASy ENZYME](https://enzyme.expasy.org/EC/2.4.2.30)). | | Substrate: CD38 | NAD+ + H2O gives ADP-ribose + nicotinamide + H+. EC 3.2.2.6, with human CD38 listed ([ExPASy ENZYME](https://enzyme.expasy.org/EC/3.2.2.6); [Rhea 16301](https://www.rhea-db.org/rhea/16301)). | | Product: NMNAT | Nicotinamide mononucleotide + ATP + H+ gives diphosphate + NAD+. EC 2.7.7.1 ([ExPASy ENZYME](https://enzyme.expasy.org/EC/2.7.7.1); [Rhea 21360](https://www.rhea-db.org/rhea/21360)). | | Product: NAD synthase | Deamido-NAD+ + L-glutamine + ATP + H2O gives L-glutamate + AMP + diphosphate + NAD+ + H+. EC 6.3.5.1 ([ExPASy ENZYME](https://enzyme.expasy.org/EC/6.3.5.1); [Rhea 24384](https://www.rhea-db.org/rhea/24384)). | | Product: NADH oxidation | Ubiquinone + NADH + 5 H+(in) gives ubiquinol + NAD+ + 4 H+(out). EC 7.1.1.2 ([ExPASy ENZYME](https://enzyme.expasy.org/EC/7.1.1.2); [Rhea 29091](https://www.rhea-db.org/rhea/29091)). | | Records checked | 6 November 2026 | NAD+ is a substrate in some reactions and a product in others. A substrate goes into an enzyme reaction. A product comes out. Public enzyme records show NAD+ on both sides of the arrow, in different reactions. This page reads those records one by one. It is part of [the NAD+ hub](/learn/nad-plus). The [what NAD+ is page](/learn/nad-plus/what-is-nad-plus) covers the molecule itself. The [NAD+ vs NMN, NADH and NADP+ page](/learn/nad-plus/nad-plus-vs-nmn-nadh-and-nadp) covers the look-alike molecules. This page covers enzyme chemistry only. It makes no claim about what a molecule does for a reader. ## Is NAD+ a substrate or a product? NAD+ is both. It is a substrate when an enzyme uses it up, and a product when an enzyme makes it. A substrate is the molecule that goes into a reaction. A product is the molecule that comes out. Covarrubias et al. describe cells that keep NAD+ in balance through making it, using it up and recycling it (2021). So the label depends on which reaction you look at. The enzyme records on this page show the pattern. Lactate dehydrogenase, sirtuins, PARPs and CD38 take NAD+ in. NMNAT enzymes, NAD synthase and complex I give NAD+ out. The sections below take them in turn. ## When is NAD+ a substrate in redox reactions? NAD+ is a substrate when a redox enzyme uses it to take up electrons. Redox means a reaction that moves electrons. ExPASy ENZYME lists L-lactate dehydrogenase (EC 1.1.1.27) with the reaction (S)-lactate + NAD+ = pyruvate + NADH + H+. NAD+ goes in and NADH comes out. NADH is the same coenzyme after it accepts electrons. [Rhea](https://www.rhea-db.org/rhea/23444) holds the same equation as reaction 23444. ChEBI lists NAD+ as C21H28N7O14P2 with charge +1 and NADH as C21H29N7O14P2 with charge 0 ([ChEBI CHEBI:15846](https://www.ebi.ac.uk/chebi/CHEBI:15846), [ChEBI CHEBI:16908](https://www.ebi.ac.uk/chebi/CHEBI:16908)). The extra hydrogen on NADH fits the electrons NAD+ took up. The equation uses an equals sign. A reaction written that way can be read in both directions. Read from right to left, NAD+ is a product. ## Which enzymes use NAD+ as a substrate and break it down? Sirtuins, PARPs and CD38 use NAD+ as a substrate and break it down. Covarrubias et al. group these as the NAD+-consuming enzymes: the NAD+ glycohydrolases (CD38, CD157 and SARM1), the sirtuins and the PARPs (2021). Each one splits NAD+ and releases nicotinamide (NAM), a small part of the molecule. ExPASy ENZYME gives each reaction an EC number, which is a standard code for an enzyme reaction. Sirtuins are listed as EC 2.3.1.286. The reaction is N(6)-acetyl-L-lysyl-[protein] + NAD+ + H2O = 2'-O-acetyl-ADP-D-ribose + nicotinamide + L-lysyl-[protein] ([Rhea 43636](https://www.rhea-db.org/rhea/43636)). PARPs are listed as EC 2.4.2.30. In that reaction, an ADP-ribose group from NAD+ goes onto an acceptor and nicotinamide is released. CD38 is listed under EC 3.2.2.6, with the reaction NAD+ + H2O = ADP-D-ribose + nicotinamide + H+ ([Rhea 16301](https://www.rhea-db.org/rhea/16301)). In all three, NAD+ is a substrate and nicotinamide is a product. This is a description of what the enzymes do to a molecule. It is not a claim about what happens in a person. ## Which enzymes make NAD+ as a product? NMNAT enzymes and NAD synthase make NAD+ as a product. ExPASy ENZYME lists nicotinamide-nucleotide adenylyltransferase (EC 2.7.7.1) with the reaction beta-nicotinamide D-ribonucleotide + ATP + H+ = diphosphate + NAD+. Covarrubias et al. name three human forms, NMNAT1, NMNAT2 and NMNAT3, that turn nicotinamide mononucleotide (NMN) into NAD+ (2021). [Rhea](https://www.rhea-db.org/rhea/21360) holds the NMNAT reaction as 21360. NAD synthase is a second maker. The glutamine-using form is EC 6.3.5.1: deamido-NAD+ + L-glutamine + ATP + H2O = L-glutamate + AMP + diphosphate + NAD+ + H+ ([Rhea 24384](https://www.rhea-db.org/rhea/24384)). A form that uses ammonia is EC 6.3.1.5 ([Rhea 21188](https://www.rhea-db.org/rhea/21188)). Covarrubias et al. say that cells recycle the nicotinamide that sirtuins, PARPs and CD38 release. The chain goes from nicotinamide to NMN and then to NAD+ (2021). So a product of one enzyme set, nicotinamide, becomes the starting material for the next. The full pathways are on [the how NAD+ is made page](/learn/nad-plus/how-is-nad-plus-made). ## Is NAD+ a product when NADH is oxidised? Yes. NAD+ is a product when an enzyme oxidises NADH, which means it removes the electrons NADH carries. ExPASy ENZYME lists NADH:ubiquinone reductase (EC 7.1.1.2), also called complex I. The reaction is a ubiquinone + NADH + 5 H+(in) = a ubiquinol + NAD+ + 4 H+(out). NADH is the substrate here and NAD+ is a product ([Rhea 29091](https://www.rhea-db.org/rhea/29091)). This reaction is the lactate dehydrogenase pattern in reverse. In the first, NAD+ takes electrons and becomes NADH. Here, NADH gives electrons away and becomes NAD+. The same coenzyme moves between two forms. Each form is a substrate for some enzymes and a product of others. ## Is NAD+ a substrate, a coenzyme or a cofactor? NAD+ is a coenzyme, and in many reactions it is also a substrate. [ChEBI](https://www.ebi.ac.uk/chebi/CHEBI:23354) defines a coenzyme as a small, non-protein organic compound that acts as a dissociable acceptor or donor of chemical groups or electrons. Dissociable means it can come off the enzyme. Covarrubias et al. call NAD+ a coenzyme for redox reactions and an essential cofactor for sirtuins, CD38 and PARPs (2021). The three words describe how an enzyme uses the molecule. In the lactate dehydrogenase record, NAD+ is a reactant that is changed into NADH. That is why the record lists it as a substrate. In the sirtuin, PARP and CD38 records, the enzyme splits NAD+ apart. A cofactor is a helper an enzyme needs. A substrate is what the enzyme works on. NAD+ fills both roles. ## Frequently asked questions ### Is NAD+ a substrate? Yes. NAD+ is a substrate of redox enzymes such as L-lactate dehydrogenase (EC 1.1.1.27) and of NAD+-consuming enzymes: sirtuins, PARPs and CD38 (ExPASy ENZYME; Covarrubias et al., 2021). In each case an enzyme uses NAD+ up. ### Is NAD+ a product? Yes. NAD+ is a product of NMNAT enzymes (EC 2.7.7.1), of NAD synthase (EC 6.3.5.1 and EC 6.3.1.5) and of NADH oxidation by complex I (EC 7.1.1.2). The ExPASy ENZYME and Rhea records list NAD+ on the product side of these reactions. ### Is NADH a substrate or a product? NADH is both, like NAD+. In lactate dehydrogenase, NADH is a product (EC 1.1.1.27). In complex I, NADH is a substrate (EC 7.1.1.2). The two forms swap roles between reactions (ExPASy ENZYME; Rhea 23444 and 29091). ### Is nicotinamide a substrate or a product in NAD+ chemistry? Nicotinamide is a product when sirtuins, PARPs and CD38 break down NAD+ (EC 2.3.1.286, EC 2.4.2.30 and EC 3.2.2.6). Covarrubias et al. describe it as the molecule that salvage steps recycle toward NMN and then NAD+ (2021). ### Does this page claim anything about what NAD+ does in a person? No. It describes what enzymes do to molecules, using public records from ExPASy ENZYME, Rhea and ChEBI. It makes no claim about what any molecule does in a person. ## Citations - Covarrubias AJ et al.. Nature Reviews Molecular Cell Biology. NAD+ metabolism and its roles in cellular processes during ageing, 2021;22(2):119-141. PubMed 33353981.. DOI: 10.1038/s41580-020-00313-x - Bairoch A.. Nucleic Acids Research. The ENZYME database in 2000, 2000;28(1):304-305. Entries for EC 1.1.1.27, 2.3.1.286, 2.4.2.30, 3.2.2.6, 2.7.7.1, 6.3.5.1 and 7.1.1.2 were read on enzyme.expasy.org on 6 November 2026.. DOI: 10.1093/nar/28.1.304 - Bansal P et al.. Nucleic Acids Research. Rhea, the reaction knowledgebase in 2022, 2022;50(D1):D693-D700. Reactions 23444, 43636, 16301, 21360, 24384, 21188 and 29091 were read on rhea-db.org on 6 November 2026.. DOI: 10.1093/nar/gkab1016 [NAD+ reference material](/shop/nad-plus) Research use only. Not for human or animal use. 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