The trick in understanding the role of enzymes is to appreciate the difference in rates between the enzyme-catalyzed reaction and the spontaneous reaction. While it's true that all enzyme-catalyzed reactions would eventually proceed even in the absence of enzyme, the rate of the spontaneous reaction might be way too slow. We often emphasize that the spontaneity of a reaction can be determined from the thermodynamics (i.e. if ΔG <0 the reaction is spontaneous) but we sometimes forget to show real data on how fast such a reaction can occur under physiological conditions. Typical rates for enzyme-catalyzed reactions are described by a constant called kcat.1 These values are usually in the range of 100-1000 reactions per second but there are some enzymes than have rates of over 1,000,000 reactions per second.
Spontaneous reactions can often approach these rates but, as you might imagine, the ones that require enzymes are very much slower. Proteins, for example, will eventually break down into amino acids but the rate of the reaction is so slow that spontaneous protein degradation is not a problem in living cells. In order to degrade proteins for food, we need to make enzymes such as chymotrypsin, trypsin, pepsin, and elastin to do the job at a faster rate.
Most of the important metabolic reactions take years in the absence of enzyme. The spontaneous degradation of a protein, for example, takes about 100 years (rate constant ~ 4 × 10-9). Since chymotrypsin catalzyes this reaction at a rate of about 1000 molecules per second, this means that the enzyme speeds up the reaction by a factor of more than 1011 (100 billion times)!
This value (1011) is sometimes called the catalytic proficiency of an enzyme although for technical reasons we won't go into here, the real measure of catalytic proficiency is higher by several orders of magnitude.1 The catalytic proficiency of chymotrypsin is 2 × 1016.
Naturally, this invites a comparison with those enzymes showing the greatest rate enhancements. But there's a problem. You can measure spontaneous rates that are on the order of a few years because you don't have to wait until the reaction goes to completion. But if the spontaneous reaction takes hundreds of years it can be difficult to measure—even the most dedicated graduate student won't wait that long!
Fortunately there are a few tricks that will make the job easier. You can observe the spontaneous reaction at high temperatures, for example, and calculate what the rate would be at physiological temperatures. That's what Radzicka and Wolfenden did in 1995 when they reported that the spontaneous decarboxylation of ornithine 5′-phosphate (OMP) had a rate constant of 3 × 10-16 s-1. This is a half-life of 78 million years.
The enzyme that catalyzes this reaction is ornithine 5′-phosphate decaboxlyase and up until last week it was the record holder with a catalytic proficiency of 2 × 1023. (OMP decarboxylase catalyzes an essential step in the synthesis of pyrimidine nucleotides that are required to make RNA and DNA.)
That record has now been broken. Lewis and Wolfenden (2008) studied a reaction catalyzed by uroporphyrinogen decarboxylase, an enzyme involved in the synthesis of porphyrins such as heme, the cofactor in hemoglobin, and the chlorophylls. There were able to model the reaction and determine that the rate of spontaneous decarboxylation is 9.5 × 10-18 s-1, which corresponds to a half-life of 2.3 billion years! Lewis and Wolfenden published a chart showing typical half-lives of spontaneous reactions.
The catalytic proficiency of uroporphyrinogen decarboxylase is 2.5 × 1024, a new record.
Into the textbook it goes.
1. A better description of an enzyme's real rate constant is kcat/Km.
Radzicka, A. and Wolfenden, R. (1995) A proficient enzyme. Science 267:90-93.
Lewis,C.A. Jr. and Wolfenden, R. (2008) Uroporphyrinogen decarboxylation as a benchmark for the catalytic proficiency of enzymes. Proc. Natl. Acad. Sci. (USA) published online November 6, 2008 [Abstract] [doi:10.1073/pnas.0809838105]