METABOLIC STRESS IN NORMAL AND ABNORMAL HUMAN RED CELLS

在人类红细胞中，当正常缓慢运动的新陈代谢发生时，压力就会发生 红血球的机械被迫加速到超出正常速度。 在被疟疾寄生的红细胞中发现代谢应激，在一些 病理状态，如骨髓增生性疾病(MPD)。 葡萄糖-6-磷酸脱氢酶缺陷型红细胞(G6PD-) 特别容易受到压力，因为它们不能增加戊糖分流 新陈代谢。这项研究打算调查的显著特征 体外感染恶性疟原虫的正常人和异常人红细胞 疟疾。特别是，G6PD-细胞抑制 将对疟疾的增长进行研究。将检验两个假设：A. 疟疾感染细胞中的氧化应激与该酶相互作用 缺乏抑制生长的能力。B.G6PD-细胞不能产生足够的核糖 磷酸盐是不断增长的寄生虫所需的核苷酸。这两个 假设并不是相互排斥的。方法论将包括 体外疟疾，膜脂过氧化敏感性测定， 将标记的前体掺入核苷酸，并对其进行研究 疟疾的增长与磷酸核糖焦磷酸供应的关系 (PRPP)--戊糖途径的关键代谢物。MPD红细胞是 以高浓度的还原型谷胱甘肽(GSH)和 糖酵解酶活性增强，在某些方面类似于未成熟的红色 细胞或脐带细胞。他们也有更多的易感性 膜脂过氧化，这与高GSH有关 内容。这种关系的性质将通过研究 粗制和提纯红细胞裂解物氧化血红蛋白和 精心设计02的主动形式。这些裂解物对密封红的影响 细胞幽灵和脂质体也将被研究。谷胱甘肽可能作为一种 在某些条件下既是促氧化剂，也是抗氧化剂。无论是或 MPD红细胞中出现的不促氧化条件仍有待于 下定决心。完整红细胞中PRPP合成酶对谷胱甘肽的需求 还将研究谷胱甘肽的合成和降解速度。 GHS的操作可能会改变MPD的进程，减少输血需求， 改善血液储存，增进知识。

In human red cells, stress occurs when the normally slow moving metabolic machinery of the red cell is forced to accelerate beyond its normal rate. Metabolic stress is found in red cells parasitized by malaria and in some pathological states such as in myeloproliferative diseases (MPD). Glucose-6-phosphate dehydrogenase deficient red cells (G6PD-) are especially vulnerable to stress because they cannot augment pentose shunt metabolism. This study intends to investigate the salient features of normal and abnormal human red cells infected in vitro with falciparum malaria. In particular, the mechanism whereby G6PD- cells inhibit the growth of malaria will be studied. Two hypotheses will be tested: A. Oxidative stress in malaria infected cells interacts with the enzyme deficiency to inhibit growth. B. G6PD- cells cannot produce enough ribose phosphate for nucleotide needs of the growing parasites. These two hypotheses are not mutually exclusive. Methodology will include culture of malaria in vitro, assays for susceptibility to membrane lipid peroxidation, incorporation of labelled precursors into nucleotides, and a study of the growth of malaria in relation to the supply of phosphoribosylpyrophosphate (PRPP) - a key metabolite of the pentose pathway. MPD red cells are characterized by high concentrations of reduced glutathione (GSH) and increased glycolytic enzyme activity and in some ways resemble immature red cells or cord cells. They also have an increased susceptibility to membrane lipid peroxidation, which is linked somehow to the high GSH content. The nature of this relationship will be explored by studying the tendency of crude and purified red cell lysates to oxidize hemoglobin and elaborate active forms of 02. The effect of these lysates on sealed red cell ghosts and liposomes will also be studied. GSH may function as a pro-oxidant as well as an anti-oxidant under some conditions. Whether or not pro-oxidant conditions occur in MPD red cells remains to be determined. The requirement of PRPP synthetase for GSH in intact red cells will also be studied as will GSH synthesis and degradation rates. Manipulations of GHS may alter the course of MPD, reduce transfusion needs, inprove blood storage, enhance knowledge.