Thinking Like an Enzyme

Judith Klinman received her PhD in chemistry at the University of Pennsylvania in 1966. She was a postdoctoral fellow at the Weizmann Institute for Science, Israel, from 1966 to 1967. In 1968, she returned to Philadelphia and proceeded to spend 10 years at the Institute for Cancer Research in Philadelphia, first as a postdoctoral associate and later as a research staff member. In 1978, she moved to the University of California, Berkeley, where she is now chancellor s professor of chemistry and of molecular and cell biology. 

A few weeks ago, my sister and I prepared a luncheon for a group of women with whom we had graduated from high school 50 ( ) years ago. We had gathered from all corners of the United States— California, Washington, DC, New York, New Jersey, and Pennsylvania— to compare notes and just to enjoy each other. I was the only scientist 

Letters to a Young Chemist, First Edition. Edited by Abhik Ghosh. 

ENZYMES—CATALYSTS FOR TRANSFORMING MOLECULES ON AMAZINGLY FAST TIMESCALES 

The most dramatic feature of enzymes is that they are highly selective catalysts, allowing reactions that would normally require years in their absence to take place in milliseconds. The upper limit for the extent that an enzyme can accelerate a reaction is estimated to be 1CF°, about the same order of magnitude as the number of observable 

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Enzymes may be inhibited in many ways, which are not within the scope of this book to discuss in detail. However, it is an important reason for variation in the disposition and toxicity of chemicals. If we think of an enzyme as a lock and the chemical it metabolizes as a key, then an inhibitor is like a bent key which becomes stuck in the lock. Alternatively it might destroy the lock (enzyme) completely. The result is that the enzyme does not work properly or at all, and the drug or chemical is not metabolized. By decreasing the detoxication and excretion this can increase the toxicity of the drug. 

Monoamine oxidase (MAO) is an enzyme produced in the human body which acts something like a chemical version of our white blood cells -that is, its function is to break down potentially destabilizing amines present in our food and render them harmless. One might think of monoamine oxidase as the active agent in a kind of "chemical immune system" which helps to regulate metabolism and maintain a healthy chemical balance in our bodies. A monoamine oxidase inhibitor (AAAOl) is... 

At the same time, a unified theory is required to explain how and why a particular treatment, or any treatment, should be effective, especially enzyme inhibitors against cancer cell metabohsm. Otherwise it all becomes more of an exercise in futility for example, there are the many herbal remedies proposed that apparently have no basis in substantiated fact other than somebody or another s word for it, is usually second or third hand, that is, is entirely anecdotal, and is as likely as not to be wishful thinking. 

If the presence of a soluble mediator shuttling the electrons between the electrode and the enzyme is to be avoided, other modes of wiring [15] the enzyme to the electrode ought to be sought after. One may think of direct electron transfer between the electrode and the enzyme at the adsorbed state. It has indeed been shown that small redox proteins, such as cytochrome c or ferredoxins may show an unmediated reversible electrochemical response when the electrode surface is adequately prepared [16-19]. There have been few reports of direct electron transfer with redox enzymes [20,21]. With flavoen-zymes, the observed signals are likely to be those of the free flavin deriving from the denaturation of the enzyme [21]. The high probability of denaturation of the adsorbed enzyme prevents the viability of this mode of electron transport in most cases. 

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