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Document “lazy”. Since there is plenty of glucose and oxygen available, they rely solely on glycolysis to the stage of pyruvate for their energy supply [12]. Their glycolysis proceeds at an amazing rate, which is about fifty times faster than in the cells of the human host [43]. This fast rate is a necessity because only two molecules of ATP are generated per molecule of glucose instead of the thirty-six produced by complete oxidation. These findings led to the proposal that inhibitors of trypanosomal glycolysis might be turned into drugs. Support for this idea comes from in vitro experiments where salicylhydroxamic acid (SHAM) was used to bring the parasite under anaerobic conditions, after which glycolysis was http://legacy.netlibrary.com/nlreader/nlReader.dll?bookid=12640&filename=Page_368.html (2 of 2) [4/5/2004 5:32:08 PM]
Document Table 2 Three-Dimensional Structures Available for Trypanosomal Drug Design (a) Glycolytic: (b) Other: Trypanosomatid PDB code Mammalian PDB code PGIa — — Porcine 1PGI[22] Aldolase — — Human b 1ALD[23] TIM T. brucei 5TIM[24] Human 1HTI[25] GAPDH T. brucei L.mexicana 1GGA[26,27] [30] PGK — — Horse Pig Human c 3GPD[28,29] 2PGK[31]—[32] PK — — Cat d 1PYK[33] TR T. cruzi 1NDA[34] HumanGR 3GRS[35] C. fasciculata 1TYT[36] 1PPR[37] HGPRT — — Human 1HMP[38] VSG T. brucei 1VSG[39] No equivalent a Abbreviations: PGI = phosphoglucose isomerase, PGK = phosphoglycerate kinase, PK = pyruvate kinase, TR = trypanothione reductase; GR = glutathione reductase, HGPRT = hypoxanthine-guanine phosphoribosyl transferase, VSG = variable surface glycoprotein. b A isoenzyme, from muscle; other mammalian isoenzymes are B in liver and C in brain. c Muscle isoenzyme; a liver isoenzyme exists. dM1 isoenzyme, from muscle; mammals also have M2 in kidney, adipose tissue and lung, L in liver, and R in rood blood cells. http://legacy.netlibrary.com/nlreader/nlReader.dll?bookid=12640&filename=Page_369.html (1 of 2) [4/5/2004 5:32:27 PM] Page 369
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Document D ddI, 152 tumour necrosis
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Document antistasin peptides, 281 c
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Document Phosphoglycerate kinase (P
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Document [Protease targets] serinyl
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