3.8. Bioorganic Example: NAD⁺/NADH

Although hydride acceptors seem highly specialized they are commonly used in biological systems for oxidation/reduction reactions. The most common of these is an enzyme cofactor called nicotinamide adenine dinucleotide (abbreviated as NAD; Figure 3.30).

Figure 3.30 – Nicotinamide Adenine Dinucleotide in the NAD⁺ Form.

Enzyme cofactors are discussed in greater detail in a subsequent chapter (see Chapter 6). As a brief simplification, cofactors are non-protein compounds that are required for an enzyme to catalyze a reaction. They are often attached to the enzyme but are not part of the amino acid chain(s) that make up the enzyme. Cofactors typically have functional groups (or atoms) that can perform certain reactions that amino acid side chains cannot.

This is the case with NAD. NAD has two forms (Scheme 3.28): NAD⁺ (“NAD with a positive charge”) and NADH (“NAD with an extra hydrogen”). These two forms are functionally identical to the intermediate and product (pyridine) 6-membered aromatic heterocycle discussed (see Section 3.7.1.2 and subsections therein).

Scheme 3.28 – Interconversion of NAD+ and NADH via Oxidation/Reduction of Propan-2-ol/Propan-2-one Highlighting Similarities to Pyridine and its Precursor.

NAD⁺ is a hydride acceptor (an oxidizer). NAD⁺ become NADH whenever the cofactor accepts a hydride (whenever the cofactor oxidizes a compound in the enzyme).

NADH is a hydride donor (a reducer). NADH become NAD⁺ whenever the cofactor donates a hydride (whenever the cofactor reduces a compound in the enzyme).