Without enzyme, vital biological reaction takes 2.3 bn years to complete

Washington, Nov 11 : A biological reaction within human cells which is essential to life can take almost 2.3 billion years - about half the age of the Earth - to complete if there's no enzyme to speed up the process.

All biological reactions within human cells depend on enzymes. Their power as catalysts enables biological reactions to occur usually in milliseconds.

But Richard Wolfenden, Ph.D., Alumni Distinguished Professor Biochemistry and Biophysics and Chemistry at the University of North Carolina at Chapel Hill, has tried to find out how slowly would these reactions proceed spontaneously, in the absence of enzymes.

In 1995 Wolfenden found that in the absence if a particular enzyme, a biological transformation he deemed "absolutely essential" in creating the building blocks of DNA and RNA would take 78 million years.

In the current study, however, he said that a reaction essential for the biosynthesis of haemoglobin and chlorophyll may take as long as 2.3 billion years to complete in the absence of the enzyme uroporphyrinogen decarboxylase.

"Now we've found a reaction that - again, in the absence of an enzyme - is almost 30 times slower than that. Its half-life - the time it takes for half the substance to be consumed - is 2.3 billion years, about half the age of the Earth. Enzymes can make that reaction happen in milliseconds," said Wolfenden. However, when catalyzed by the enzyme uroporphyrinogen decarboxylase, the rate of chlorophyll and haemoglobin production in cells "is increased 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."

"This enzyme is essential for both plant and animal life on the planet. What we're defining here is what evolution had to overcome, that the enzyme is surmounting a tremendous obstacle, a reaction half-life of 2.3 billion years," Wolfenden said.

He added that the knowledge of how long reactions would take without enzymes allows biologists to appreciate their evolution as prolific catalysts and also enables scientists to compare enzymes with artificial catalysts produced in the laboratory.

"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," he said.

Experimental methods for observing very slow reactions can also generate important information for rational drug design based on cellular molecular studies.

Research on enzymes as proficient catalysts also led to the design of protease inhibitors that are used to treat HIV infection.

The study is published in the online early edition of the Proceedings of the National Academy of Science.

ANI