A Proficient Enzyme

TLDR

Orotic acid decarboxylation in neutral aqueous solution at room temperature has a half‑life of about 78 million years. Spontaneous hydrolysis of phosphodiester bonds is extremely slow (e.g., dimethyl phosphate t½ ≈ 1.3 × 10⁵ yr), extending the known range of spontaneous rate constants by over 14 orders of magnitude, whereas the enzyme Orotidine 5′‑phosphate decarboxylase accelerates the reaction by ~10¹⁷‑fold and binds the transition‑state substrate with a dissociation constant below 5 × 10⁻²⁴ M, keeping catalytic rate constants within a 600‑fold range.

Abstract

Orotic acid is decarboxylated with a half-time (t 1/2 ) of 78 million years in neutral aqueous solution at room temperature, as indicated by reactions in quartz tubes at elevated temperatures. Spontaneous hydrolysis of phosphodiester bonds, such as those present in the backbone of DNA, proceeds even more slowly at high temperatures, but the heat of activation is less positive, so that dimethyl phosphate is hydrolyzed with a t 1/2 of 130,000 years in neutral solution at room temperature. These values extend the known range of spontaneous rate constants for reactions that are also susceptible to catalysis by enzymes to more than 14 orders of magnitude. Values of the second-order rate constant k cat / K m for the corresponding enzyme reactions are confined to a range of only 600-fold, in contrast. Orotidine 5′-phosphate decarboxylase, an extremely proficient enzyme, enhances the rate of reaction by a factor of 10 17 and is estimated to bind the altered substrate in the transition state with a dissociation constant of less than 5 × 10 -24 M.