In: Nature , vol 228, 1970, p 868
Similar Functions of Uric Acid and Ascorbate in Man
Pointing out the structural similarity between uric acid and the stimulant purines caffeine and theophylline, Orowan (1) first proposed that the emergence of intelligence in the primate line might arise from a single evolutionary event, the loss of the enzyme uricase, with the result that uric acid became the end product of purine metabolism. The only non-primate mammalian strain whose final purine metabolite is uric acid is the Dalmatian dog.
Haldane( 2) , taking issue with this suggestion, proposed two hypotheses: that individuals with high serum uric acid levels should show increased intellectual abilities , and that such individuals should be unusually resistant to certain types of fatigue. Neither one of these has received much experimental support, Although serum uric acid levels have been correlated with social class, achievment, and achievement -oriented behavior. ( for a review of such work, see Muller et al (3).
I would like to propose that the loss of uricase in the primate line may be connected with another biochemical lesion which is unique to the primates, namely, the loss of the ability to synthesise ascorbic acid de novo. As in the case of loss of uricase, this lesion is found in only one non-primate mammalian species ( the guinea pig (4) ). (Post-publication addendum: also the flying fox).
The reasoning behind this suggestion is this: a number of the physiological functions of ascorbate are generally considered to be related to the unique electron-donor properties of this compound. Uric acid ( along with the rest of the purines ) is also a strong electron-donor (5). In fact, on the somewhat tenuous basis of molecular orbital indices, uric acid may be a better electron-donor than is ascorbate.(6). It therefore seems possible that ( in primates at least ) uric acid has taken over some of the functions of ascorbate. This suggestion is not to deny any other physiological or psychological function for uric acid, but is advanced to suggest an evolutionary mechanism for the loss of the ability to synthesize ascorbate de novo ( the latter lesion might not be very important in a fruit-eating animal except in times of famine or in the event of a change in diet. ). Any further selective advantage of higher systemic levels of uric acid would tend to establish the double lesion in the population.
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Behavioral Pharmacology Division
Texas Research Institute of Mental Sciences
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Received April 27, 1970
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1) Orowan, E. Nature 175, 683 (1955)
2) Haldane, J.B.S. Nature, 176, 169 (1955)
3) Mahler, E.F., Kasl, S.V., Brooks, G.W., and Cobb, S. Psychol. Bull. 73,238 (1970 )
4) Mahler, H.r., and Cordes, E.H., Biological Chemistry, 475 ( Harper and Row, New York, 1966.
5) Pullman, B, and Pullmans, A., Quantum Biochemistry, 217 ( Academic Press, New York, 1963 ).
6) ) Pullman, B, and Pullmans, A., Quantum Biochemistry, 707 ( Academic Press, New York, 1963 )