Enzyme: Mechanisms

What are the properties of enzymes?

● Enzymes are biological catalysts that alter reaction rates without changing the overall delta G or K_eq and are not consumed by the reaction. Substrates bind with high specificity to the enzyme active site, which is a cleft or pocket in the protein structure where the catalyzed reaction takes place.

● Stabilizing the transition state is one of the key mechanisms of enzyme catalysis and is the molecular basis for tight binding of transition state analogs, which often function as enzyme inhibitors.

● The activation energy (delta G^‡) is the difference between the ground state energy of the reactant and the transition state energy. Enzymes lower delta G^‡ by providing a favorable physical and chemical environment in the active site to promote catalysis.

● Cofactors provide additional reactive groups to the enzyme active site that complement the limited chemistry of amino acid side chains. Some cofactors are inorganic ions. Organic cofactors are called coenzymes, many of which are derived from vitamins.

How do enzymes function as biological catalysts in cells?

● Enzymes lower the activation energy ( delta G^‡) of a reaction in three different ways: (1) by stabilizing the transition state, which lowers the activation barrier; (2) by providing an alternative path for product formation through reaction intermediates; and (3) by orienting the substrates appropriately for the reaction to occur.

● Functional groups in the active site mediate three main types of catalytic reaction mechanisms: (1) acid–base catalysis, (2) covalent catalysis, and (3) metal-ion catalysis.

● Enzymes perform three main types of work in the cell: (1) coenzyme-dependent redox reactions associated with energy conversion; (2) metabolite transformation reactions to interconvert metabolites in anabolic and catabolic pathways; and (3) reversible covalent modification reactions to control cell signaling processes and enzyme activity.

● Enzyme-catalyzed redox reactions in the cell often require coenzymes such as NAD⁺/NADH, NADP⁺/NADPH, FAD/FADH₂, or FMN/FMNH₂. These redox reactions involve the transfer of a pair of electrons or a single electron through a radical intermediate.

● Metabolite transformations in metabolic pathways most often involve isomerization reactions, condensation reactions, or hydrolysis or dehydration reactions.

● One of the most common types of reversible covalent modification reactions in cells is the addition and removal of a phosphoryl group in biomolecules. Enzymes that attach phosphoryl groups are called kinases, and enzymes that remove phosphoryl groups are called phosphatases.