ENZYME-SUBSTKATE COMBINATION 37 



prevent the enzyme-substrate attachment, as would alteration 

 of the carbon chain length between them as this would place 

 the two — NHg groups at the wrong distance apart to orientate 

 and attach to the combining groups of the enzyme surface. 

 Such a substrate-enzyme relation would also explain optical 

 specificity as it is obvious that the laevo- and dextro- forms 

 of the substrate would not " fit " on to the same combining 

 group structure. This hypothesis that the substrate and 

 enzyme-surface have to fit or interlock in an exact position 

 has given rise in the past to the analogy of a lock and key, 

 in that the one must fit the other before any further action 

 can occur. 



If the combining groups on the surface of the enzyme are 

 almost, but not quite, in the right position to " fit " the polar 

 groups of the substrate, then the resulting enzyme-substrate 

 combination will introduce a strain into the structure of the 

 substrate and so render it more unstable. Haldane has 

 suggested that the properties of enzyme action can be explained 

 by such enzyme-substrate combinations which result in the 

 production of a strain in the substrate molecule and facilitate 

 its chemical alteration. 



COMPETITIVE INHIBITION 

 i The substrate of an enzyme therefore is any substance 

 which can combine reversibly with the right groups on the 

 enzyme surface. The reversible nature of the combination 

 is important, for if we can find a substance whose structure 

 is such that it can combine with the combining-groups on 

 the enzyme surface but which is not strained, altered, and 

 released as is the true substrate, then this substance will 

 remain on the surface of the enzyme, block the essential links, 

 and so prevent the true substrate froln combining. The net 

 result of this is that the breakdown of the substrate is inhibited 

 and such a substance is called a " competitive inhibitor." 

 An example of a competitive inhibitor is malonic acid, 

 HOOC.CHg.COOH, which combines with succinic dehydro- 

 genase and inhibits the dehydrogenation of the true substrate, 



