METABOLISM AND FUNCTIONS OF TRYPANOTHIONE IN THE KINETOPLASTIDA

被引:327
作者
FAIRLAMB, AH
CERAMI, A
机构
[1] Department of Medical Parasitology, London Sch. of Hyg. and Trop. Med., London WC1E 7HT, Keppel Street
[2] Picower Inst. for Medical Research, Manhasset, NY 11034
基金
英国惠康基金;
关键词
GLUTATHIONE; POLYAMINES; FLAVOPROTEIN DISULFIDE OXIDOREDUCTASES; CHEMOTHERAPY; PROTOZOAN PARASITES;
D O I
10.1146/annurev.mi.46.100192.003403
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Trypanosomatids differ from all other organisms in their ability to conjugate the sulfur-containing tripeptide, glutathione, and the polyamine, spermidine, to form trypanothione [N1,N8-bis(glutathionyl)spermidine]. Together with the NADPH-dependent flavoprotein, trypanothione reductase, the dithiol form of trypanothione provides an intracellular reducing environment in these parasites, substituting for glutathione and glutathione reductase found in the mammalian host. Trypanothione and its related enzymes are involved in defense against damage by oxidants, certain heavy metals, and possibly xenobiotics. Trypanothione and its metabolic precursor, glutathionylspermidine, are also implicated in the modulation of spermidine levels during growth. Several existing trypanocidal drugs interact with the trypanothione system, suggesting that trypanothione metabolism may be a good target for the development of new drugs. The purification and properties of three key enzymes (glutathionylspermidine synthetase, trypanothione synthetase, and trypanothione reductase) are discussed, and the catalytic mechanism, substrate-specificity, and the three-dimensional structure of trypanothione reductase are compared to that of glutathione reductase.
引用
收藏
页码:695 / 729
页数:35
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