Kosubstrat

Kosubstrat, commonly written as cosubstrate, is a concept in enzymology describing a molecule that participates in an enzyme-catalyzed reaction together with the primary substrate. The cosubstrate is typically not the main target of the reaction; instead, it provides a reactive component or energy that is transferred during the catalytic step and then regenerated by other parts of metabolism so that the enzyme can continue to function.

Cosubstrates are usually not tightly bound to the enzyme. They bind reversibly, undergo a chemical transformation during the reaction, and are restored to their original state by the overall metabolic context. This distinguishes cosubstrates from tightly bound cofactors or prosthetic groups, which remain attached to the enzyme throughout catalysis.

Common examples include nucleotide cofactors such as NAD+ or NADP+ in dehydrogenase reactions, which accept electrons and are reduced to NADH or NADPH; ATP in kinase reactions, which donates a phosphate group; and CoA derivatives in acyl transfer reactions. In these cases, the primary substrate is the molecule being transformed, while the cosubstrate provides the necessary chemical functionality and is regenerated after the reaction.

Terminology can vary, and some authors use cosubstrate more broadly to refer to any co-occurring substrate that is consumed and regenerated, while others reserve the term for smaller, transient molecules. In all usages, the core idea is that a cosubstrate participates in the enzymatic transformation and is not permanently altered as part of the enzyme’s structure.