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范式的局限性:克氏锥虫中间代谢的研究

The limitations of paradigms: studies on the intermediary metabolism of Trypanosoma cruzi.

作者信息

Urbina J A, Machin I, Jurado L

机构信息

Laboratorio de Química Biológica, Instituto Venezolano de Investigaciones Científicas, Caracas.

出版信息

Biol Res. 1993;26(1-2):81-8.

PMID:7670550
Abstract

We review the development of our knowledge and interpretations of the intermediary metabolism of Trypanosoma (Schizotrypanum) cruzi. Already in the 1950's it was clearly established that when this organism was exposed to large external concentrations of carbohydrates it was unable to catabolize them completely, even in the presence of oxygen, producing a mixture of CO2, dicarboxylic acids (succinic, malic) and alanine as end products. However, subsequent work tended to emphasize such paradigmatic features as a full complement of glycolytic enzymes in all stages of the life cycle of the parasite, a functional Kreb's cycle, a cytochrome-dependent electron transport chain and phosphorylative oxidation which suggested that T. cruzi had the basic metabolic properties of classical glucose-utilizing cells, in contrast with the degenerate glycolytic metabolism of bloodstream African trypanosomes. Only in the 1980's interest revived on the how and why of the incomplete carbohydrate catabolism by this parasite. The primary reason for this anomaly was found to be the presence of a constitutive phospho-enol-pyruvate carboxykinase (PEPCK, ATP-dependent, E.C.4.1.1.49), present in all stages of the parasite's life cycle, and the lack of regulation of the glycolytic route at its classical control points, hexokinase and phosphofructokinase. On the other hand, the presence of two distinct glutamate dehydrogenases (NAD+ and NADP(+)-dependent), the former being strictly regulated by the energy charge of the cell and the Krebs' cycle activity, indicated that amino acids can be a primary source of energy for this organism.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

我们回顾了对克氏锥虫(裂殖锥虫属)中间代谢的认识和解读的发展历程。早在20世纪50年代就已明确,当这种生物体暴露于高浓度的外源碳水化合物时,即使在有氧的情况下,它也无法将其完全分解代谢,最终产物是二氧化碳、二羧酸(琥珀酸、苹果酸)和丙氨酸的混合物。然而,随后的研究倾向于强调一些典型特征,比如在寄生虫生命周期的所有阶段都有完整的糖酵解酶补充、一个功能性的三羧酸循环、一个细胞色素依赖性电子传递链以及磷酸化氧化,这表明克氏锥虫具有经典的利用葡萄糖细胞的基本代谢特性,这与非洲血液中的锥虫退化的糖酵解代谢形成对比。直到20世纪80年代,人们才重新关注这种寄生虫不完全碳水化合物分解代谢的方式和原因。发现这种异常的主要原因是在寄生虫生命周期的所有阶段都存在一种组成型磷酸烯醇丙酮酸羧激酶(PEPCK,依赖ATP,E.C.4.1.1.49),以及在经典控制点己糖激酶和磷酸果糖激酶处糖酵解途径缺乏调控。另一方面,存在两种不同的谷氨酸脱氢酶(依赖NAD⁺和NADP⁺),前者严格受细胞能量电荷和三羧酸循环活性的调节,这表明氨基酸可能是这种生物体的主要能量来源。(摘要截选至250词)

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1
The limitations of paradigms: studies on the intermediary metabolism of Trypanosoma cruzi.范式的局限性:克氏锥虫中间代谢的研究
Biol Res. 1993;26(1-2):81-8.
2
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Trypanosoma cruzi phospho enol pyruvate carboxykinase (ATP-dependent): transition metal ion requirement for activity and sulfhydryl group reactivity.克氏锥虫磷酸烯醇丙酮酸羧激酶(ATP 依赖性):活性对过渡金属离子的需求及巯基反应性
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The crystal structure of Trypanosoma cruzi glucokinase reveals features determining oligomerization and anomer specificity of hexose-phosphorylating enzymes.克氏锥虫葡萄糖激酶的晶体结构揭示了决定己糖磷酸化酶寡聚化和异头物特异性的特征。
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Biochemical characterization of new strains of Trypanosoma cruzi and T. rangeli isolates from Peru and Mexico.来自秘鲁和墨西哥的克氏锥虫及兰氏锥虫新菌株的生化特性
Parasitol Res. 2004 Oct;94(4):294-300. doi: 10.1007/s00436-004-1214-5. Epub 2004 Sep 11.
2
Glucose is toxic to glycosome-deficient trypanosomes.葡萄糖对缺乏糖体的锥虫有毒性。
Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14177-82. doi: 10.1073/pnas.222454899. Epub 2002 Oct 17.