Structural Biochemistry/Enzyme/sequential reactions

Definition

Sequential reactions are one of the classes involved in multiple substrate reactions. In these types of reactions, all the substrates involved are bound to the enzyme before catalysis of the reaction takes place to release the products. Sequential reactions can be either ordered or random. In a bisubstrate reaction, a ternary complex of the enzyme and both substrates forms.

Ordered Sequential Reactions

In ordered sequential reactions, all the substrates are first bound to the enzyme in a defined order or sequence. The products, too, are released after catalysis in a defined order or sequence.

An example is the lactate dehydrogenase enzyme, which is a protein that catalyzes glucose metabolism. In this ordered mechanism, the coenzyme, NADH, always binds first, with pyruvate binding afterward. During the reaction, the pyruvate is reduced to lactate while NADH is oxidized to NAD⁺ by the enzyme. Lactate is then released first, followed by the release of NAD⁺.

This is a characteristic of a ternary complex, which consists of three molecules that are bound together. Before catalysis, the substrates and coenzyme are bound to the enzyme. After catalysis, the complex consists of the enzyme and products, NAD⁺ and lactate.

Random Sequential Reactions

In random sequential reactions, the substrates and products are bound and then released in no preferred order, or "random" order. An example is the creatine kinase enzyme, which catalyzes the substrates, creatine and ATP, to form the products, phosphocreatine and ADP. In this case, either substrates may bind first and either products may be released first.

A ternary complex is still observed for random sequential reactions. Before catalysis, the complex includes the enzyme, ATP and creatine. After catalysis, the complex consists of the enzyme, ADP, and phosphocreatine.