Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00492 (hypoxanthine-guanine phosphoribosyltransferase)
 2,385 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasmodium falciparum trophozoites were isolated by mechanical rupture of infected human erythrocytes followed by a series of differential centrifugation steps. After lysis with sonication, the 100 000 x g supernatant of parasites and uninfected host cells was used to determine the specific activities of a number of enzymes involved in purine and pyrimidine metabolism. P. falciparum possessed the purine salvage enzymes: adenosine deaminase, purine nucleoside phosphorylase, hypoxanthine-guanine phosphoribosyltransferase (PRTase), xanthine PRTase, adenine PRTase, adenosine kinase. The last two enzymes, however, were present at much lower activity levels. Hypoxanthine was converted (presumably via IMP) into adenine and guanine nucleotides only in the presence both of supernatant and membrane fractions of P. falciparum. Two enzymes involved in the de novo synthesis of pyrimidines, orotic acid PRTase, and orotidine 5'-phosphate decarboxylase, were present in parasite extracts as were the enzymes for pyrimidine nucleotide phosphorylation: UMP-CMP kinase, dTMP kinase, nucleoside diphosphate kinase. Xanthine oxidase, CTP synthetase, cytidine deaminase and several kinases for the salvage of pyrimidine nucleosides were not detected in the parasites. Both phosphoribosyl pyrophosphate synthetase and uracil PRTase were present but at low activity levels. Human erythrocytes displayed similar but not identical enzyme patterns. Enzyme specific activities, however, were generally much lower than those of the corresponding parasite enzymes.
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PMID:Enzymes of purine and pyrimidine metabolism from the human malaria parasite, Plasmodium falciparum. 628 90

Anaphase promoting complex/cyclosome (APC/C)-mediated proteolysis is essential for chromosome segregation, mitotic exit, and G1 entry. Here, we show the importance of APC/C in the control of dTTP pool size in mammalian cells. Two enzymes, thymidine kinase 1 (TK1) and thymidylate kinase (TMPK), involved in dTTP formation are the targets of the APC/C pathway. We demonstrate that TMPK is recognized and degraded by APC/C-Cdc20/Cdh1-mediated pathways from mitosis to the early G1 phase, whereas TK1 is targeted for degradation by APC/C-Cdh1 after mitotic exit. Overexpression of wild-type TK1 and TMPK induces a four- to fivefold increase in the cellular dTTP pool without promoting spontaneous mutations in the hprt (hypoxanthine-guanine phosphoribosyl transferase) gene. In contrast, coexpression of nondegradable TK1 and TMPK expands the dTTP pool size 10-fold accompanied by a drastic dNTP pool imbalance. Most interestingly, disruption of APC/C proteolysis of TK1 and TMPK leads to growth retardation and a striking increase in gene mutation rate. We conclude that down-regulation of dTTP pool size by the APC/C pathway during mitosis and the G1 phase is an essential means to maintain a balanced dNTP pool and to avoid genetic instability.
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PMID:Control of dTTP pool size by anaphase promoting complex/cyclosome is essential for the maintenance of genetic stability. 1610 19