PYRIMIDINE METABOLISM IN MAN. III. STUDIES ON LEUKOCYTES AND ERYTHROCYTES IN PERNICIOUS ANEMIA*†

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Abstract
Studies were carried out on the cellular levels of 3 enzymes involved in pyrimidine synthesis (aspartate carbamyltrans-ferase (AC), dihydroorotase, and dihydroorotic dehydrogenase) in circulating erythrocytes and leukocytes from 10 patients with pernicious anemia in relapse. Enzymatic levels of AC and dihydroorotase were elevated. Dihydroorotic dehydrogenase activity was normal. These abnormalities returned to normal after treatment with B12. It is suggested from analogous results obtained by Yates and Pardee using Escherichia coli mutants that there is a state of "pyrimidine starvation" during B12 deficiency. This leads to release of a negative feedback controlling mechanism with resulting compensatory increase in the activities of earlier enzymes. Attempts to demonstrate a 2d type of feedback control in erythrocytes and leukocytes, the competitive inhibition of AC by cytidine-5[image]-phosphate, were unsuccessful, although this mechanism was readily confirmed in E. coli.