INHIBITION OF THE BIOSYNTHESIS OF THE PYRIMIDINE PORTION OF THIAMINE BY ADENOSINE

Abstract

Moyed , H. S. (Harvard Medical School, Boston, Mass.). Inhibition of the biosynthesis of the pyrimidine portion of thiamine by adenosine. J. Bacteriol. 88: 1024–1029. 1964.—The bacteriostatic effects of adenosine and several other purines on Aerobacter aerogenes can be overcome by either thiamine or the pyrimidine portion of thiamine. Adenosine causes almost complete cessation of the synthesis of the pyrimidine and consequently also of thiamine. However, synthesis of deoxyribonucleic acid, ribonucleic acid, and protein persists in the absence of thiamine synthesis until a three-or fourfold increase has occurred, indicating that A. aerogenes has a surplus supply of either thiamine or the pyrimidine. The failure of cells to continue production of the thiazole portion of thiamine when the synthesis of the pyrimidine is blocked indicates that control over the thiazole is exerted by the thiazole itself rather than by the intact thiamine molecule. Bacteria blocked in the synthesis of the pyrimidine either as the result of mutation or because of inhibition by adenosine excrete an intensely fluorescent, but as yet unidentified, compound. The fluorescent compound bears the nutritional relationship to the pyrimidine characteristic of that between an intermediate and an end product: an excess of the pyrimidine prevents its formation, whereas a deficiency of the pyrimidine greatly stimulates its formation. Adenosine inhibition of the synthesis of the pyrimidine is partially relieved by histidine or succinate. It is suggested that these compounds either bypass the blocked reaction or participate in the detoxification of adenosine.