World record enzymes

by Jonathan Sarfati

One vital class of proteins is enzymes, which are catalysts, i.e. they speed up chemical reactions without being consumed in the process. Without them, many reactions essential for life would be far too slow for life to exist. Catalysts do not affect the equilibrium, but only the rate at which equilibrium is reached. They work by lowering the activation energy, which means decreasing the energy of a transitional state or reaction intermediate.

Rate enhancement by 10¹⁸

Enzyme expert Dr Richard Wolfenden, of the University of North Carolina, showed in 1998 that a reaction ‘“absolutely essential” in creating the building blocks of DNA and RNA would take 78 million years in water’, but was speeded up 10¹⁸ times by an enzyme.¹ This was orotidine 5′-monophosphate decarboxylase, responsible for de novo synthesis of uridine 5′-phosphate, an essential precursor of RNA and DNA, by decarboxylating orotidine 5′-monophosphate (OMP).²

The enzyme has a special shape, a TIM-barrel. This binds the substrate at the open end of the barrel, while protein loop movements almost totally surround the substrate. The enzyme has amino acid residues in just the right places to interact with the functional groups on the substrate. One lysine is provides a positive charge to interact with the increasing negative charge as the substrate reacts, and provides a proton which replaces carboxylate group at C-6 of the product. And the enzyme is structured so that some hydrogen bonds form and delocalize negative charge in the transition state, lowering the energy. Interactions between the enzyme and the phosphoribosyl group anchor the pyrimidine within the active site, helping to explain the phosphoribosyl group’s remarkably large contribution to catalysis despite its distance from the site of decarboxylation. Still other interactions hold the pyrimidine within the active site, which also contributes greatly to the catalysis although it is far from the site of decarboxylation.

Rate enhancement by 10²¹

In 2003, Wolfenden found another enzyme exceeded even this vast rate enhancement. A phosphatase, which catalyzes the hydrolysis of phosphate dianions, magnified the reaction rate by thousand times more than even that previous enzyme—10²¹ times. That is, the phosphatase allows reactions vital for cell signalling and regulation to take place in a hundredth of a second. Without the enzyme, this essential reaction would take a trillion years—almost a hundred times even the supposed evolutionary age of the universe (about 15 billion years)!³

Implications

Wolfenden said,

Actually, it should make one wonder about the faith commitment to evolution from goo to you via the zoo, in the face of such amazingly fine-tuned enzymes vital for even the simplest life! And natural selection can’t operate until there are already living organisms to pass on the information coding for the enzymes, so it cannot explain the origin of these enzymes.

Update: in 2008, Dr Wolfenden co-authored a paper on another enzyme,⁴ which speeds up another essential reaction that would take 2.3 billion years. This one is ‘essential to the biosynthesis of hemoglobin and chlorophyll’, and it is sped up ‘by a staggering factor, one that’s equivalent to the difference between the diameter of a bacterial cell and the distance from the Earth to the sun.’⁵

References and notes

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