Pyrimidine Metabolism in Man. II. Studies of Leukemic Cells

Abstract

1. The activities of three enzymes involved in pyrimidine synthesis— aspartate carbamyltransferase, dihydro-orotase and dihydro-orotic dehydrogenase—were studied in sonicates of circulating leukocytes from 5 patients with myelocytic leukemia, 2 with lymphocytic leukemia, 2 with myeloproliferative disorders and 5 with infection. The erythrocytes from one patient with the Di Guglielmo syndrome were studied. 2. Neoplastic cells showed increased activities of all three enzymes tending to parallel the cytologic evidence of immaturity. The increase of dihydroorotic dehydrogenase was the most striking abnormality. Leukocytes from patients with infection or with myeloproliferative disorders showed similar but much less marked alterations in the enzyme pattern. 3. Dihydro-orotic dehydrogenase, absent from mature erythrocytes, was present in the nucleated erythrocytes in the Di Guglielmo syndrome. 4. The enzyme 5 carboxymethylhydantoinase, previously found in some bacteria, was absent from normal and abnormal hemic cells.

Human neural progenitor cells decrease photoreceptor degeneration, normalize opsin distribution and support synapse structure in cultured porcine retina

“…The relevance of DHODH in cancer was first reported in 1960 when its high expression was seen in leukemia cells (128). Afterwards, several investigations that had encouraging results in preclinical studies led to the discovery of the potent DHODH inhibitor, brequinar (129).…”