General John B. McClennan had a bad case of “the slows.” So said Abraham Lincoln early in the Civil War when “Prince John” wasn’t moving fast enough for his commander-in-chief.
But when it really comes to the slows, some biological reactions would be hard to beat, especially those that occur in the absence of the catalyzing power of enzymes.
How slowly would these transformations occur — days, weeks, months? And why even pose the question?
One UNC scientist who studies such issues is Richard Wolfenden, Ph.D., Alumni Distinguished Professor of biochemistry and biophysics and a member of the National Academy of Sciences.
According to a study he reported four years ago, a biological reaction considered essential in creating the building blocks of DNA and RNA would take 78 million years without a particular enzyme.
But another transformation in the absence of an enzyme Wolfenden recently described in PNAS is almost 30 times slower than that, roughly 2.3 billion years, or almost half the age of planet Earth. Now ain’t that “the slows.”
This reaction is essential for the biosynthesis of hemoglobin and chlorophyll. But when catalyzed by the enzyme uroporphyrinogen decarboxylase, the rate of cholorophyll and hemoglobin production in cells is increased by a staggering factor — equivalent to the difference between the diameter of a bacterial cell and the distance from Earth to the sun.
“Enzymes allow organisms to channel the flow of matter to their own advantage, allowing some reactions to proceed rapidly compared with others that offer no selective advantage,” says Wolfenden. He points out that after a substance is bound at an enzyme’s active site, it’s half-life, the time it takes for half the substance to be consumed, is usually a small fraction of one second.
According to the researcher, rapid turnover is necessary if any enzyme is to produce a significant rate of reaction given their limited concentration witin cells. “Not surprisingly , many enzymes have evolved to work nearly as efficiently as is physcially possible, with second order rate constants that approach their rates of encounter with the substrate in solution.”
Particularly remarkable are those cases in which enymes act alone as simple protein catalysts.
So why bother with wanting to know the rate of slowness of reactions in the absence of enzymes? For one, the information would allow biologists to appreciate what natural selection has accomplished in the evolution of enzymes as proficient catalysts, Wolfenden explains.
And such information has also found direct application in the development of ‘transition state analogue inhibitors,’ leading to the design of drugs such as the ACE inhibitors that are now used to control high blood pressure and the protease inhibitors that are used to treat HIV infection.
But if that’s not enough, there’s always this: Without enzymes as catalysts, there would be no life at all, neither microbial nor human.