寄生原生动物中的苹果酸脱氢酶:在新陈代谢中的作用和潜在的治疗应用。

IF 5.6 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Essays in biochemistry Pub Date : 2024-10-03 DOI:10.1042/EBC20230075
Amy L Springer, Swati Agrawal, Eric P Chang
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引用次数: 0

摘要

本文综述了苹果酸脱氢酶(MDH)在各种具有医学意义的原生动物寄生虫代谢过程中的作用。MDH 是一种依赖于 NADH 的氧化还原酶,可催化草酰乙酸和苹果酸之间的相互转化,为分解代谢和合成代谢途径提供代谢中间产物,并可促进多个细胞区的 NAD+/NADH 平衡。MDH 几乎存在于所有生物体中;本文介绍了来自无丝复合体(恶性疟原虫、弓形虫、隐孢子虫属)、锥虫(布氏锥虫、克鲁兹锥虫)和厌氧原生动物(阴道毛滴虫、十二指肠贾第虫)的 MDH 同工酶。许多寄生物种具有复杂的生命周期,并依赖宿主环境中的碳源和其他营养物质。代谢可塑性对寄生虫在宿主环境之间的转换至关重要;因此,调节代谢过程是探索治疗干预的一个重要领域。原生动物寄生虫新陈代谢的共同主题包括强调糖酵解代谢、底物级磷酸化、三羧酸循环等常见途径的非传统使用以及线粒体类细胞器的适应或减少。我们描述了 MDH 异构体在这些途径中的作用,讨论了这些异构体与活性或药物靶向相关的不寻常结构或功能特征,并回顾了目前探索 MDH 及相关基因的治疗潜力的研究。这些研究表明,MDH 活性在许多代谢途径中具有重要作用,因此在原生动物寄生虫作为病原体成功所需的代谢转换中也具有重要作用。
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Malate dehydrogenase in parasitic protozoans: roles in metabolism and potential therapeutic applications.

The role of malate dehydrogenase (MDH) in the metabolism of various medically significant protozoan parasites is reviewed. MDH is an NADH-dependent oxidoreductase that catalyzes interconversion between oxaloacetate and malate, provides metabolic intermediates for both catabolic and anabolic pathways, and can contribute to NAD+/NADH balance in multiple cellular compartments. MDH is present in nearly all organisms; isoforms of MDH from apicomplexans (Plasmodium falciparum, Toxoplasma gondii, Cryptosporidium spp.), trypanosomatids (Trypanosoma brucei, T. cruzi) and anaerobic protozoans (Trichomonas vaginalis, Giardia duodenalis) are presented here. Many parasitic species have complex life cycles and depend on the environment of their hosts for carbon sources and other nutrients. Metabolic plasticity is crucial to parasite transition between host environments; thus, the regulation of metabolic processes is an important area to explore for therapeutic intervention. Common themes in protozoan parasite metabolism include emphasis on glycolytic catabolism, substrate-level phosphorylation, non-traditional uses of common pathways like tricarboxylic acid cycle and adapted or reduced mitochondria-like organelles. We describe the roles of MDH isoforms in these pathways, discuss unusual structural or functional features of these isoforms relevant to activity or drug targeting, and review current studies exploring the therapeutic potential of MDH and related genes. These studies show that MDH activity has important roles in many metabolic pathways, and thus in the metabolic transitions of protozoan parasites needed for success as pathogens.

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来源期刊
Essays in biochemistry
Essays in biochemistry 生物-生化与分子生物学
CiteScore
10.50
自引率
0.00%
发文量
105
审稿时长
>12 weeks
期刊介绍: Essays in Biochemistry publishes short, digestible reviews from experts highlighting recent key topics in biochemistry and the molecular biosciences. Written to be accessible for those not yet immersed in the subject, each article is an up-to-date, self-contained summary of the topic. Bridging the gap between the latest research and established textbooks, Essays in Biochemistry will tell you what you need to know to begin exploring the field, as each article includes the top take-home messages as summary points. Each issue of the journal is guest edited by a key opinion leader in the area, and whether you are continuing your studies or moving into a new research area, the Journal gives a complete picture in one place. Essays in Biochemistry is proud to publish Understanding Biochemistry, an essential online resource for post-16 students, teachers and undergraduates. Providing up-to-date overviews of key concepts in biochemistry and the molecular biosciences, the Understanding Biochemistry issues of Essays in Biochemistry are published annually in October.
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