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
Without catalysts, there would be no life at all, from microbes to humans. It makes
you wonder how natural selection operated in such a way as to produce a protein
that got off the ground as a primitive catalyst for such an extraordinarily slow
reaction.
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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
Decarboxylation of orotidine 5΄-monophosphate (OMP) to uridine 5΄-phosphate
(UMP), an essential precursor of RNA and DNA, by the enzyme 5΄-monophosphate
decarboxylase.
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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,
‘Without catalysts, there would be no life at all, from microbes to humans.
It makes you wonder how natural selection operated in such a way as to produce a
protein that got off the ground as a primitive catalyst for such an extraordinarily
slow reaction.’1
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.
References and notes
- Cited in Lang, L.H.,
Without Enzyme Catalyst, Slowest Known Biological Reaction Takes 1 Trillion Years,
Biocompare Life Science News, 5 May 2003. Return to text.
- Miller, B.G., Hassell, A.M., Wolfenden, R., Milburn, M.V. and Short,
S.A.,
Anatomy of a proficient enzyme: The structure of orotidine 5'-monophosphate decarboxylase
in the presence and absence of a potential transition state analog, Proceedings
of the National Academy of Science 97(5):2011–2016,
29 February 2000. Return to text.
- Lad, C., Williams, N.H. and Wolfenden, R., The
rate of hydrolysis of phosphomonoester dianions and the exceptional catalytic proficiencies
of protein and inositol phosphatases, Proceedings of the National Academy of
Science 100(10):5607–5610, 13 May 2003. Return
to text.
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