Organic chemistry enzymology

Measuring isotope effects on enzyme chemistry requires a careful integration of enzymology and organic chemistry. Enzymology is crucial to ensure that kinetic... 

Department of Organic Chemistry and Enzymology Communication No. 281. The experimental work in Fordham was carried out under the auspices of the Office of Naval Research, the Atomic Energy Commission and the National Science Foundation. 

Department of Organic Chemistry and Enzymology Fordham University, New York 58, N.Y. 

Nevertheless, the full-blown mechanism that showed the role of the coenzyme was only written out in detail by Braunstein and M. M. Shemyakin in 1953 (Braunstein and Shemyakin, 1952, 1953). Their formulae (2), complete with the curved arrow notation of physical organic chemistry, clearly pointed out the role of the coenzyme as an electron sink in a ketimine mechanism. They showed how the coenzyme can function in transamination, racemization and, with some help from Hanke and his collaborators (Mandeles et al 1954), in decarboxylation. The mechanisms they advanced were exactly what we would postulate today, and constituted an early and successful application of theory to mechanistic enzymology. But it must be admitted that the theory appealed because it was reasonable the authors had little or no evidence, in terms of physical organic chemistry, to support their formulation, which is shown in part below. 

Mechanistic enzymology has developed at a rapid pace since 1963, and the artificial catalysts of which Fischer spoke in 1902 appear within the realm of possibility (Breslow, 1982). Enzymologists now have reasonable notions of mechanism and of the factors needed to achieve rapid rates and specificity. Nevertheless, the foundations for mechanism and to some extent for an understanding of the factors relevant to enzymology were laid down in the years 1947-1963. By the end of that time, enzymology had become incorporated into physical organic chemistry. 

Comprehensive discussions are to be found in (a) M. L. Bender, Mechanisms of Homogeneous Catalysis from Protons to Proteins, Wiley, New York, 1971 (b) W. P. Jencks, Catalysis in Chemistry and Enzymology, McGraw-Hill, New York, 1969 (c) M. L. Bender, Ckem. Rev., 60, 53 (1960). For more specialized treatments of particular aspects, see (d) W. P. Jencks, Chem. Rev., 72, 705 (1972), general acid-base catalysis (e) S. L. Johnson, Advan. Phys. Org. Chem., 5,237 (1967), ester hydrolysis (f) L. P. Hammett, Physical Organic Chemistry, 2nd ed., McGraw-Hill, New York, 1970, chap. 10, acid—base catalysis. 

Many other applications of electrochemical methods for chemical characterization are presented in the following chapters. The state of utilization is such that for many research groups in the fields of organic chemistry and inorganic chemistry, electrochemistry has become a characterization tool as essential as infrared and NMR spectroscopy. This is quickly becoming true for several areas of biochemistry, especially enzymology. 

Since the details of this proof are somewhat involved, it is worthwhile to review the procedure. The work provides a classic example of the interplay between organic chemistry, biochemistry, enzymology and microbiology. 

A major addition to the second edition is Chapter 9, which discusses computational enzymology. This chapter extends the coverage of quantum chemistry to a sister of organic chemistry—biochemistry. Since computational biochemistry truly deserves its own entire book, this chapter presents a flavor of how computational quantum chemical techniques can be applied to biochemical systems. This chapter presents a few examples of how QM/MM has been applied to understand the nature of enzyme catalysis. This chapter concludes with a discussion of de novo design of enzymes, which is a research area that is just becoming feasible, and one that will surely continue to develop and excite a broad range of chemists for years to come. 

Silverman RB. Mechanism-Based Enzyme Inactivation Chemistry and Enzymology, Vols. I and II. 1988. CRC Press, Boca Raton, FL. Silverman RB. The Organic Chemistry of Enzyme-Catalyzed Reactions. 

J. Retey and J. A. Robinson, Stereospecificity in Organic Chemistry and Enzymology, H. F. Ebel (ed.), Verlag Chemie, Weinheim, 1982, pp 185. 

David Vander Jagt (1942-) received his doctor of philosophy (PhD) in 1967 in synthetic/mechanistic organic chemistry at Purdue University (West Lafayette, Indiana), in the laboratory of the Nobel Laureate H. C. Brown. After Purdue, he took a post-doctoral position at Northwestern University (Chicago, Illinois) in the laboratory of M. L. Bender in bioorganic chemistry/enzymology (1967-1969). When the opportunity came for a joint appointment in the Department of Biochemistry,... 

A. Comish-Bowden, Principles of enzyme kinetics, Butterworth Co., London, 1976. J.A. Robinson,). Retey, Stereospecificity in organic chemistry and enzymology, VCH Verlag, Weinheim 1982. 

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