Showing papers by "Albert H. van Gennip published in 1991"
TL;DR: In man pyrimidines are degraded in four steps catalysed by dihydropyrimidine dehydrogenase, which is easily detected by classical amino acid analysis 1’2, DHPD-deficiency by TLC or HPLC of pyridines in urine3, and a method is presented for the detection of the two other defects.
Abstract: In man pyrimidines are degraded in four steps catalysed by dihydropyrimidine dehydrogenase (DHPD, EC 1. 3. 1. 2.), dihydropyrimidinase (DHP, EC 3. 5. 2. 2.), ureidopropionase (UP, EC 3. 5. 1. 6.) and a transaminase (Fig. 1). As yet only deficiencies of the first and the last enzymes have been described. Deficiency of R-s-aminoisobutyrate aminotransferase (EC 2. 6. 1. 22.) is easily detected by classical amino acid analysis 1’2,DHPD-deficiency by TLC or HPLC of pyrimidines in urine3. A method is presented for the detection of the two other defects.
5 citations
TL;DR: It is concluded that drugs interfering with CTP-synthetase activity are good candidates to be used as selective substances in the battle against T-ALL.
Abstract: Knowledge of transformation associated differences in pyrimidine nucleotide metabolism of human leukemic cells, compared to healthy counterparts can be a rational basis for development of new antileukemic drugs. Peripheral blood cells of patients with acute lymphoblastic leukemia (ALL) contain increased amounts of guanine-, uracil- and cytosine- nucleotides and uridinediphosphate bound sugars with a changed composition. Moreover, the same deviations have also been found in the human ALL cell-line of T-lymphoblastic origin MOLT-3. Comparison of pyrimidine nucleotide synthesis from labeled precursors by MOLT-3 cells and growth-stimulated T-lymphocytes (TL’s), showed that CTP-synthetase ‘overactivity’ could cause the increase in cytosine nucleotides found in the malignant cell-line cells2. Uridine fluxes by pulse-chase experiments in living cells with emphasis on CTP-synthetase activity and differences herein between MOLT-3 cells, TL’s and differentiated resting MOLT-3 cells, were performed to get a better insight in the fluxes and the role of CTP-synthetase.