核苷二磷酸激酶强烈促进细胞内GDP和ADP代谢,并影响线粒体内源性质子泄漏-该激酶受到氧化磷酸化抑制剂的阻碍。

IF 5.4 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Andrzej M Woyda-Ploszczyca
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引用次数: 0

摘要

假设从野生型酵母中分离的线粒体中快速的GDP代谢。外源性GDP的标志是与外源性ADP的作用趋同,通常诱导氧化磷酸化(OXPHOS)。在ATP存在的情况下,GDP引起的变化,即呼吸频率增加伴随着线粒体内膜电位下降,被OXPHOS抑制剂(如羧白术苷)所抑制,这些抑制剂显然将GDP效应与OXPHOS结合在一起。然而,所有进行的测试表明,线粒体对GDP的反应是间接的,涉及两个步骤。首先,GDP通过核苷二磷酸激酶(NDPK)转磷酸化,ATP + GDP→ADP + GTP,然后是ADP诱导的OXPHOS。重要的是,从缺失NDPK基因的突变酵母中分离的线粒体中,GDP的刺激作用被消除了。因此,GDP代谢作用的先决条件是NDPK与OXPHOS装置的配合。这种生物学模型可以帮助阐明一些疾病治疗的分子基础,如癌症。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Nucleoside diphosphate kinase strongly promotes GDP and ADP metabolism in the cell and affects endogenous proton leak in mitochondria - the kinase is hampered by oxidative phosphorylation inhibitors.

Nucleoside diphosphate kinase strongly promotes GDP and ADP metabolism in the cell and affects endogenous proton leak in mitochondria - the kinase is hampered by oxidative phosphorylation inhibitors.

Nucleoside diphosphate kinase strongly promotes GDP and ADP metabolism in the cell and affects endogenous proton leak in mitochondria - the kinase is hampered by oxidative phosphorylation inhibitors.

Nucleoside diphosphate kinase strongly promotes GDP and ADP metabolism in the cell and affects endogenous proton leak in mitochondria - the kinase is hampered by oxidative phosphorylation inhibitors.

Rapid GDP metabolism in mitochondria isolated from wild-type yeast is postulated. The hallmark of exogenous GDP is convergence with the effect of exogenous ADP, typically inducing oxidative phosphorylation (OXPHOS). The GDP-provoked changes in the presence of ATP, i.e. increased respiratory rate accompanied by decreased inner mitochondrial membrane electrical potential, were curtailed by OXPHOS inhibitors, such as carboxyatractyloside, which apparently merged the GDP effect with OXPHOS. However, all performed tests indicated that the response of mitochondria to GDP is indirect and involves two steps. First, GDP is transphosphorylated via nucleoside diphosphate kinase (NDPK), ATP + GDP → ADP + GTP, which is followed by ADP-induced OXPHOS. Importantly, in mitochondria isolated from mutant yeast with a deleted NDPK gene, the stimulatory effect of GDP was eliminated. Therefore, a prerequisite for GDP metabolic action is the cooperation of NDPK with the OXPHOS apparatus. This biological model can help elucidate the molecular basis of some diseases treatment, such as cancer.

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来源期刊
CiteScore
10.30
自引率
10.70%
发文量
195
审稿时长
4-8 weeks
期刊介绍: Journal of Enzyme Inhibition and Medicinal Chemistry publishes open access research on enzyme inhibitors, inhibitory processes, and agonist/antagonist receptor interactions in the development of medicinal and anti-cancer agents. Journal of Enzyme Inhibition and Medicinal Chemistry aims to provide an international and interdisciplinary platform for the latest findings in enzyme inhibition research. The journal’s focus includes current developments in: Enzymology; Cell biology; Chemical biology; Microbiology; Physiology; Pharmacology leading to drug design; Molecular recognition processes; Distribution and metabolism of biologically active compounds.
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