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Inhibition of Krebs cycle and activation of glyoxylate cycle in the course of chronological aging of Saccharomyces cerevisiae. Compensatory role of succinate oxidation

机译:在酿酒酵母按时间顺序老化的过程中,抑制克雷布斯循环并激活乙醛酸循环。琥珀酸氧化的补偿作用

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We investigated oxidative processes in mitochondria of Saccharomyces cerevisiae grown on ethanol in the course of chronological aging. We elaborated a model of chronological aging that avoids the influence of exhaustion of medium, as well as the accumulation of toxic metabolites during aging. A decrease in total respiration of cells and, even more, of the contribution of respiration coupled with ATP-synthesis was observed during aging. Aging is also related with the decrease of the contribution of malonate-insensitive respiration. Activities of citrate-synthase (CS), α-ketoglutarate dehydrogenase (KGDH) and malate dehydrogenase (MDH) were threefold decreased. The activity of NADP-dependent isocitrate dehydrogenase (NADP-ICDH) decreased more significantly, while the activity of NAD-dependent isocitrate dehydrogenase (NAD-ICDH) fell even greater, being completely inactivated on the third week of aging. In contrast, succinate dehydrogenase (SDH), enzymes of glyoxylate cycle (GCL) (isocitrate lyase (ICL) and malate synthase (MLS)), and enzymes of ethanol oxidation (alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ACDH)), were activated by 50% or more. The behavior of oxidative enzymes and metabolic pathways are apparently inherent to a more viable, long-lived cells in population, selected in the course of chronological aging. This selection allows cells to reveal the mechanism of their higher viability as caused by shunting of complete Krebs cycle by glyoxylate cycle, with a concomitant increased rate of the most efficient energy source, namely succinate formation and oxidation. Thiobarbituric-reactive species (TAR species) increased during aging. We supposed that to be the immediate cause of damage of a part of yeast population. These data show that a greater succinate contribution to respiration in more active cells is a general property of yeast and animal tissues.
机译:我们调查了酿酒酵母线粒体中按时间顺序老化过程中的氧化过程。我们精心设计了一种按时间顺序老化的模型,该模型避免了培养基耗尽和老化过程中有毒代谢产物的积聚。在衰老期间,观察到细胞总呼吸的减少,甚至呼吸作用与ATP合成结合的减少。衰老还与丙二酸不敏感呼吸作用的降低有关。柠檬酸合酶(CS),α-酮戊二酸脱氢酶(KGDH)和苹果酸脱氢酶(MDH)的活性降低了三倍。依赖NADP的异柠檬酸脱氢酶(NADP-ICDH)的活性下降更为明显,而依赖NAD的异柠檬酸脱氢酶(NAD-ICDH)的活性下降更大,在衰老的第三周被完全灭活。相反,琥珀酸脱氢酶(SDH),乙醛酸循环酶(GCL)(异柠檬酸裂合酶(ICL)和苹果酸合酶(MLS))和乙醇氧化酶(酒精脱氢酶(ADH)和乙醛脱氢酶(ACDH))是被激活50%或更多。氧化酶的行为和代谢途径显然是按时间顺序老化的过程中选择的更具生存力,寿命更长的细胞所固有的。这种选择使细胞能够揭示由乙醛酸循环将完整的克雷布斯循环分流所引起的更高存活力的机制,同时伴随着最有效能源的比率增加,即琥珀酸盐的形成和氧化。在老化过程中,硫代巴比妥酸反应性物种(TAR物种)增加。我们认为这是造成一部分酵母菌种群损坏的直接原因。这些数据表明,琥珀酸在更多活性细胞中对呼吸作用的贡献是酵母和动物组织的一般特性。

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