How does NAD+ function as an enzyme cofactor?

    Last Updated: May 16, 2025

    Nicotinamide adenine dinucleotide (NAD+) functions as an enzyme cofactor by participating in redox reactions, where it accepts electrons and is reduced to NADH, which is essential for various metabolic processes. Additionally, some enzymes consume NAD+ and convert it into other forms, such as nicotinamide, which can be recycled back to NMN, and examples include sirtuins and PARPs.

    Enzymes are simply proteins that are folded into a configuration that allows them to bind other molecules and compounds, catalyzing chemical reactions. Often they can’t accomplish this catalysis alone—many enzymes also require cofactors (aka coenzymes) to function.

    The way that NAD+ functions as an enzyme cofactor depends on the enzyme. First, NAD+ helps to catalyze ‘redox’ (reduction-oxidation) reactions by accepting electrons from other compounds and molecules, becoming reduced (gaining electrons) in the process and forming the compound NADH. The reduction of NAD+ to NADH is critical for a number of enzymes and pathways associated with metabolic regulation and energy homeostasis.

    Second, some enzymes consume NAD+ in the course of carrying out their catalytic function, converting NAD+ into other forms. In many cases, NAD+-consuming enzymes convert NMN to nicotinamide, which can later be recycled back to NMN. Some examples are the class of enzymes known as sirtuins, which have anti-aging activity,[1] and poly (ADP-ribose) polymerases (PARPs), which help to repair DNA damage.