Fischer, Emil enzyme action

As already mentioned, the glucoamylase project was chosen to illustrate Emil Fischer s lock and key concept for enzyme specificity. It is seen that his vision has become unequivocally established. Many other developments could have been chosen, as can be appreciated from recent reviews by Hehre (54) and by Svensson (55). Comforth (56) provided a fine overview of asymmetry and enzyme action in his Nobel prize lecture. Noteworthy is the conclusion that stereospecificity is something not just incidental, but essential to enzyme catalysis. In other words, the key must fit the lock. 

One of the earliest, simplest, and best-known examples of this concept is the lock-and-key model of enzyme action hrst proposed by German chemist Emil Fischer (1852-1919) in 1894. While it has been significantly modihed since that time, the general mode of action suggested by Fischer is probably generally correct for most types of enzyme action. According to the lock-and-key model, illustrated below. 

An understanding of enzyme action requires not only a knowledge of pathway and rates, but also an explanation of specificity. The dominant idea in this area was that of Emil Fischer, who described the enzyme-substrate complex in terms of lock and key (Fischer, 1894). In essence, Fischer presented a steric model where a cavity in the enzyme was assumed to be shaped to fit the substrate and to hold it firmly in place. This model served enzymologists well for decades and helped them to visualize the interactions between specific... 

The lock-and-key model of enzyme action, introduced by Emil Fischer in 1890, partially accounts for enzyme specificity. Each enzyme binds to a single type... 

German chemist Emil Fischer (1852-1919) proposes the lock-and-key mechanism to explain enzyme action. 

The "lock-and-key" description of the catalytic action of enzymes given by Emil Fischer [13] one hundred years ago, put more emphasis on the enzyme-substrate specificity than on stereospecificity, suggesting the idea of ... 

From about 1894 onwards Emil Fischer investigated in a series of experiments the action of different enzymes using several glycosides and ohgosaccharides the results revealed specificity as one of the key characteristics of ertzymes. In 1894 he compared Invertin and Emulsin. He extracted Invertin from yeast, a usual procedure, and showed... 

The second aspect refers to the protein nature of enzymes. In 1894 Fischer (Fischer, 1909) stated that amongst the agents which serve the living cell the proteins are the most important. He was convinced that enzymes are proteins. The role of this key problem may be illustrated with a citation from Fruton (1979) ... the peptide theory was indeed only a hypothesis fifty years after Franz Hofmeister and Emil Fischer advanced it... (in 1902). The nature and stracture of proteins remained unknown throughout the 19th century remarkably, technological applications were nevertheless put into practice since the middle of the century (see above), based on their action, eventually recognized as catalysis, only. 

This points to two separate factors in the specificity of the activating mechanism. The structure of the active patch must first be one which will adsorb the particular substance to be activated, and second, it must activate the substance, once adsorbed. Emil Fischer s comparison of the action of an enzyme on its substrate, to the highly specific relation between a lock and key, now seems capable of being analysed further the key must not only be capable of entering the keyhole (adsorption), but it must be capable, once inserted, of operating the mechanism inside (activation). 

Since the proposition of the lock-and-key analogy by Emil Fischer (1894) several attempts have been done to understand the basis of enzymatic action. The key factor of rate acceleration by enzymes with a factor of 10IW or more (Kraut, 1977) has been thought to be the fit of transition state to the enzyme active site (Haldane, 1930 Pauling, 1946), however, it is still somewhat unclear what do we mean by the term fit. What are the real factors leading to the stabilisation of the transition state ... 

The pr e-Woodwardhn era largely concerned itself with the collection and classification of synthetic tools chemical reactions suited to broad application to the constitutional construction of molecular skeletons (including Kiliani s chain-extension of aldoses, reactions of the aldol type, and cycloadditions of the Diels-Alder type). The pre- Woodwardian era is dominated by two synthetic chemists Emil Fischer and Robert Robinson. Emil Fischer was emphasizing the importance of synthetic chemistry in biology as early as 1907 [30]. He was probably the first to make productive use of the three-dimensional structures of organic molecules, in the interpretation of isomerism phenomena in carbohydrates with the aid of the Van t Hoff and Le Bel tetrahedron model (cf. family tree of aldoses in Scheme 1-6), and in the explanation of the action of an enzyme on a substrate, which assumes that the complementarily fitting surfaces of the mutually dependent partners are noncovalently bound for a little while to one another (shape complementarity) [31],... 

An enzyme is typically a large protein molecule that contains one or more active sites where interactions with substrates take place. These sites are structurally compatible with specific substrate molecules, in much the same way as a key fits a particular lock. In fact, the notion of a rigid enzyme structure that binds only to molecules whose shape exactly matches that of the active site was the basis of an early theory of enzyme catalysis, the so-called lock-and-key theory developed by the German chemist Emil Fischer in 1894 (Figure 13.28). Fischer s hypothesis accounts for the specificity of enzymes, but it contradicts research evidence that a single enzyme binds to substrates of different sizes and shapes. Chemists now know that an enzyme molecule (or at least its active site) has a fair amount of structural flexibility and can modify its shape to accommodate more than one type of substrate. Figure 13.29 shows a molecular model of an enzyme in action. 

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