Ogston, Alexander

While a pro-chiral molecule is achiral, its two equivalent groups can be distinguished if it interacts with a chiral receptor. This was noted by Alexander Ogston, who explained why the two identical -CH2-COO groups in pro-chiral citrate are distinguished by the enzyme aconitase. One -CH2-COO group of citrate is derived from oxaloacetate, while the... 

Hans Krebs, the discoverer of the cycle, also pondered this question and at one stage came to the conclusion that citrate could not be an intermediate in the cycle. However, in 1948, Alexander ( Sandy ) Ogston provided the explanation, called the three-point attachment proposal, that was to initiate the concept of prochirality. If citrate is represented as a three-dimensional structure, as in Fig. 10-29, then on the assumption that a three-point attachment to a surface in aconitase is necessary for catalysis, it is seen that citrate can only be accommodated in one orientation. The removal of the elements of water can then only occur from one particular half of the symmetric molecule. Thus a combination of the binding site and the pro-chiral citrate is, overall, asymmetric or has handedness. 

Citric acid played a major role in the development of the concept of prochirality. Its two CH2CO2H chains groups behave differently in a key step of the Krebs cycle, so differently that some wondered whether citric acid itself were really involved. Alexander Ogston (Oxford) provided the answer in 1948 when he pointed out that the two CH2CO2H groups are differentiated when citric acid interacts with the chiral environment of an enzyme. 

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