Metabolic Flexibility and Essentiality of the Tricarboxylic Acid Cycle in Plasmodium.

IF 4 2区 医学 Q2 CHEMISTRY, MEDICINAL ACS Infectious Diseases Pub Date : 2025-02-14 Epub Date: 2025-01-27 DOI:10.1021/acsinfecdis.4c00788
Arpitha Suryavanshi, Anusha Chandrashekarmath, Nivedita Pandey, Hemalatha Balaram
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Abstract

The complete tricarboxylic acid (TCA) cycle, comprising a series of 8 oxidative reactions, occurs in most eukaryotes in the mitochondria and in many prokaryotes. The net outcome of these 8 chemical reactions is the release of the reduced electron carriers NADH and FADH2, water, and carbon dioxide. The parasites of the Plasmodium spp., belonging to the phylum Apicomplexa, have all the genes for a complete TCA cycle. The parasite completes its life cycle across two hosts, the insect vector mosquito and a range of vertebrate hosts including humans. As the niches that the parasite invades and occupies in the two hosts vary dramatically in their biochemical nature and availability of nutrients, the parasite's energy metabolism has been accordingly adapted to its host environment. One such pathway that shows extensive metabolic plasticity in parasites of the Plasmodium spp. is the TCA cycle. Recent studies using isotope-tracing targeted-metabolomics have highlighted conserved and parasite-specific features in the TCA cycle. This Review provides a comprehensive summary of what is known of this central pathway in the Plasmodium spp.

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完整的三羧酸(TCA)循环包括一系列 8 个氧化反应,发生在大多数真核生物的线粒体和许多原核生物中。这 8 个化学反应的净结果是释放出还原电子载体 NADH 和 FADH2、水和二氧化碳。疟原虫寄生于疟原虫门,具有完整 TCA 循环的所有基因。寄生虫在两个宿主(昆虫媒介蚊子和包括人类在内的一系列脊椎动物宿主)之间完成其生命周期。由于寄生虫入侵和占据的两个宿主的生境在生化性质和营养物质的可用性方面存在巨大差异,寄生虫的能量代谢也相应地适应了宿主环境。TCA 循环就是疟原虫寄生体内显示出广泛代谢可塑性的途径之一。最近利用同位素追踪靶向代谢组学进行的研究强调了 TCA 循环中的保守特征和寄生虫特异特征。本综述全面总结了目前已知的疟原虫体内这一中心途径。
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来源期刊
ACS Infectious Diseases
ACS Infectious Diseases CHEMISTRY, MEDICINALINFECTIOUS DISEASES&nb-INFECTIOUS DISEASES
CiteScore
9.70
自引率
3.80%
发文量
213
期刊介绍: ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to: * Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials. * Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets. * Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance. * Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents. * Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota. * Small molecule vaccine adjuvants for infectious disease. * Viral and bacterial biochemistry and molecular biology.
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