THYMIDYLATE SYNTHETASE-ACTIVITY IN NORMAL AND BRUGIA-PAHANGI-INFECTED AEDES-AEGYPTI

被引:5
作者
JAFFE, JJ
CHRIN, LR
机构
[1] Department of Pharmacology, University of Vermont College of Medicine, Burlington
基金
美国国家卫生研究院;
关键词
D O I
10.1016/0006-2952(79)90633-6
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Thymidylate synthetase (5,10-methylenetetrahydrofolate: dUMP C-methyltransferase; EC 2.1.2.45; TMPS) activity was detected in crude extracts of 4 to 5 day-old adult male and uninfected female Aedes aegypti. Mosquito TMPS was strongly inhibited by Mg2+ and Ca2+ (id50 values of 0.25 and 0.12 μM, respectively) but not by other divalent cations. The Km values for dUMP and 5, 10-methylene-tetrahydrofolate were 55 and 100 μM, respectively. It appeared that mosquito TMPS would not be subject to regulation by physiological concentrations of thymidine mono-, di- and triphosphates or di- and triphosphates of cytidine, uridine, adenosine or guanosine. When subjected to Sephadex G-200 gel filtration, TMPS activity occurred in three peaks, corresponding to molecular weights of 210,000, 310,000 and 450,000. Among a variety of compounds tested as inhibitors of the enzyme, FdUMP was the most potent, with an id50 value of 0.5 nM; by contrast, FUdR was inactive at 1.0 mM. The polycyclic sulfonated anionic drug, suramin, was also a strong inhibitor of mosquito TMPS, with an id50 value of 0.3 μM. Various 2,4-diaminoheterocyclic antifols, including methotrexate, either were inactive or were relatively weak inhibitors of this enzyme. The total activity of TMPS did not change in extracts of female mosquitoes prepared 7 and 12 days after they fed upon either normal or Brugia pahangi-infected jirds. © 1979.
引用
收藏
页码:1831 / 1835
页数:5
相关论文
共 25 条
[1]  
BERTINO JR, 1962, J BIOL CHEM, V237, P1314
[2]  
BLAKLEY RL, 1969, BIOCH FOLIC ACID REL, P236
[3]  
Bridges R.G., 1972, Advances Insect Physiol, V9, P51, DOI 10.1016/S0065-2806(08)60275-1
[4]  
CHALABI KA, 1977, BIOCHIM BIOPHYS ACTA, V481, P71
[5]  
CHELLO PL, 1976, CANCER RES, V36, P2442
[6]  
Chen P., 1966, ADV INSECT PHYSIOL, P53, DOI DOI 10.1016/S0065-2806(08)60186-1
[7]  
CRUSBERG TC, 1970, J BIOL CHEM, V245, P5292
[8]  
FRIDLAND A, 1971, J BIOL CHEM, V246, P7110
[9]  
GREENBERG D, 1961, J BIOL CHEM, V236, P2271
[10]  
HARRAP KR, 1971, ANN NY ACAD SCI, V186, P312