Biological Catalysts

Enzymes and ribozymes are essential to life. These macromolecules catalyze a vast array of chemical reactions that, in the absence of the biocatalyst, would take place at very low intrinsic and uncoordinated rates incompatible with life.

Biocatalysts control the complex chemistry of thousands of life processes through acceleration and regulation of the rates of virtually every chemical reaction important to life. Prevention of unwanted chemical reactions relies on keeping reactive molecules apart through compartmentalization or on binding of the chemicals to macromolecules that stabilize their desired forms.

The magnitudes of rate enhancement brought about by biocatalysts approach astronomical values. For example, at 25 °C uncatalyzed hydrolysis of phosphodiester linkages between nucleotides in DNA proceeds with a half-life (t_1/2) of 30 000 000 years (Schroeder et al., 2006).

The refractory nature of phosphodiester linkages between nucleotides in DNA permits preservation of genetic information for hundreds of thousands, if not millions, of years. Yet biological processes at times require certain phosphodiester linkages in DNA to be cleaved. Staphylococcal nuclease, one of the enzymes that catalyzes DNA-hydrolysis, functions with a turnover number of 95 s^-1, corresponding to a t_1/2 of 7 ms.

This enormous rate difference, or enzymatic enhancement factor, of 1.4 x 10¹⁷ corresponds to typical values for enzymes, and is neither the minimum nor the maximum. Nonenzymatic counterparts of certain enzymatic reactions are too slow to measure, so that only lower limits of rate enhancements for those reactions can be estimated.

In life, individual biocatalytic rates must be coordinated, and they must change under varying cellular developmental, metabolic, and environmental conditions. Coordination arises through several mechanisms. In genetic regulation, the relative amounts of enzymes produced by gene transcription and translation can be regulated to produce the appropriate amounts of metabolically or developmentally related enzymes. In metabolic control, metabolites regulate the activities of key enzymes through allosteric effects upon binding to regulatory sites of key enzymes.

For example, in end-product inhibition the enzyme catalyzing the first committed step in a metabolic or biosynthetic pathway is often inhibited by the end product of that pathway, thereby shutting it down once the end product rises to an optimal concentration. The intra-organelle microenvironments in cells can activate or inhibit certain enzymes. For example, the acidic environments in lysosomes activate pH-dependent proteolytic enzymes.

Posttranslational modifications of enzymes such as reversible phosphorylation of specific amino acid side chains are also important control mechanisms. These regulatory processes orchestrate the best balance of enzymatic activities to support the life of an organism.