Essays in biochemistry最新文献_第4页

Catalytic mechanism and kinetics of malate dehydrogenase. 苹果酸脱氢酶的催化机制和动力学。

IF 5.6 2区生物学

Essays in biochemistry Pub Date : 2024-10-03 DOI: 10.1042/EBC20230086

Laura de Lorenzo, Tyler M M Stack, Kristin M Fox, Katherine M Walstrom

引用次数: 0

Malate dehydrogenase in parasitic protozoans: roles in metabolism and potential therapeutic applications. 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

Essays in biochemistry Pub Date : 2024-10-03 DOI: 10.1042/EBC20230075

Amy L Springer, Swati Agrawal, Eric P Chang

{"title":"Malate dehydrogenase in parasitic protozoans: roles in metabolism and potential therapeutic applications.","authors":"Amy L Springer, Swati Agrawal, Eric P Chang","doi":"10.1042/EBC20230075","DOIUrl":"10.1042/EBC20230075","url":null,"abstract":"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.","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":" ","pages":"235-251"},"PeriodicalIF":5.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phosphorylation of mammalian cytosolic and mitochondrial malate dehydrogenase: insights into regulation. 哺乳动物细胞质和线粒体苹果酸脱氢酶的磷酸化：对调控的见解。

IF 5.6 2区生物学

Essays in biochemistry Pub Date : 2024-10-03 DOI: 10.1042/EBC20230079

Joseph J Provost, Kathleen A Cornely, Pamela S Mertz, Celeste N Peterson, Sophie G Riley, Harrison J Tarbox, Shree R Narasimhan, Andrew J Pulido, Amy L Springer

{"title":"Phosphorylation of mammalian cytosolic and mitochondrial malate dehydrogenase: insights into regulation.","authors":"Joseph J Provost, Kathleen A Cornely, Pamela S Mertz, Celeste N Peterson, Sophie G Riley, Harrison J Tarbox, Shree R Narasimhan, Andrew J Pulido, Amy L Springer","doi":"10.1042/EBC20230079","DOIUrl":"10.1042/EBC20230079","url":null,"abstract":"Malate dehydrogenase (MDH) is a key enzyme in mammalian metabolic pathways in cytosolic and mitochondrial compartments. Regulation of MDH through phosphorylation remains an underexplored area. In this review we consolidate evidence supporting the potential role of phosphorylation in modulating the function of mammalian MDH. Parallels are drawn with the phosphorylation of lactate dehydrogenase, a homologous enzyme, to reveal its regulatory significance and to suggest a similar regulatory strategy for MDH. Comprehensive mining of phosphorylation databases, provides substantial experimental (primarily mass spectrometry) evidence of MDH phosphorylation in mammalian cells. Experimentally identified phosphorylation sites are overlaid with MDH's functional domains, offering perspective on how these modifications could influence enzyme activity. Preliminary results are presented from phosphomimetic mutations (serine/threonine residues changed to aspartate) generated in recombinant MDH proteins serving as a proof of concept for the regulatory impact of phosphorylation. We also examine and highlight several approaches to probe the structural and cellular impact of phosphorylation. This review highlights the need to explore the dynamic nature of MDH phosphorylation and calls for identifying the responsible kinases and the physiological conditions underpinning this modification. The synthesis of current evidence and experimental data aims to provide insights for future research on understanding MDH regulation, offering new avenues for therapeutic interventions in metabolic disorders and cancer.","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":" ","pages":"183-198"},"PeriodicalIF":5.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Malate dehydrogenase in plants: evolution, structure, and a myriad of functions. 植物中的苹果酸脱氢酶：进化、结构和多种功能。

IF 5.6 2区生物学

Essays in biochemistry Pub Date : 2024-10-03 DOI: 10.1042/EBC20230089

Lisa M Baird, Christopher E Berndsen, Jonathan D Monroe

引用次数: 0

Genetics of MDH in humans. 人类 MDH 遗传学。

IF 5.6 2区生物学

Essays in biochemistry Pub Date : 2024-10-03 DOI: 10.1042/EBC20230078

Adam Haberman, Celeste N Peterson

引用次数: 0

Malate dehydrogenase (MDH) in cancer: a promiscuous enzyme, a redox regulator, and a metabolic co-conspirator. 癌症中的苹果酸脱氢酶（MDH）：一种杂合酶、氧化还原调节器和代谢共谋者。

IF 5.6 2区生物学

Essays in biochemistry Pub Date : 2024-10-03 DOI: 10.1042/EBC20230088

Betsy Leverett, Shane Austin, Jason Tan-Arroyo

引用次数: 0

Exploring the uncharted territory of the potential protein-protein interactions of cytosolic malate dehydrogenase. 探索细胞膜苹果酸脱氢酶潜在蛋白质间相互作用的未知领域。

IF 5.6 2区生物学

Essays in biochemistry Pub Date : 2024-10-03 DOI: 10.1042/EBC20230083

Joseph J Provost, Amy D Parente, Kristin M Slade, Thomas J Wiese

引用次数: 0

Is the TCA cycle malate dehydrogenase-citrate synthase metabolon an illusion? TCA 循环苹果酸脱氢酶-柠檬酸合成酶代谢物是假象吗？

IF 5.6 2区生物学

Essays in biochemistry Pub Date : 2024-10-03 DOI: 10.1042/EBC20230084

Joy Omini, Taiwo Dele-Osibanjo, Heejeong Kim, Jing Zhang, Toshihiro Obata

{"title":"Is the TCA cycle malate dehydrogenase-citrate synthase metabolon an illusion?","authors":"Joy Omini, Taiwo Dele-Osibanjo, Heejeong Kim, Jing Zhang, Toshihiro Obata","doi":"10.1042/EBC20230084","DOIUrl":"10.1042/EBC20230084","url":null,"abstract":"This review discusses the intriguing yet controversial concept of metabolons, focusing on the malate dehydrogenase-citrate synthase (MDH-CISY) metabolon as a model. Metabolons are multienzyme complexes composed of enzymes that catalyze sequential reactions in metabolic pathways. Metabolons have been proposed to enhance metabolic pathway efficiency by facilitating substrate channeling. However, there is skepticism about the presence of metabolons and their functionality in physiological conditions in vivo. We address the skepticism by reviewing compelling evidence supporting the existence of the MDH-CISY metabolon and highlighting its potential functions in cellular metabolism. The electrostatic interaction between MDH and CISY and the intermediate oxaloacetate, channeled within the metabolon, has been demonstrated using various experimental techniques, including protein-protein interaction assays, isotope dilution studies, and enzyme coupling assays. Regardless of the wealth of in vitro evidence, further validation is required to elucidate the functionality of MDH-CISY metabolons in living systems using advanced structural and spatial analysis techniques.","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":" ","pages":"99-106"},"PeriodicalIF":5.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Uncovering malate dehydrogenase: structure, function and role in disease. 揭示苹果酸脱氢酶：结构、功能和在疾病中的作用。

IF 5.6 2区生物学

Essays in biochemistry Pub Date : 2024-10-03 DOI: 10.1042/EBC20240044

Celeste N Peterson, Kathleen Cornely, Amy D Parente, Amy L Springer, Joseph J Provost

{"title":"Uncovering malate dehydrogenase: structure, function and role in disease.","authors":"Celeste N Peterson, Kathleen Cornely, Amy D Parente, Amy L Springer, Joseph J Provost","doi":"10.1042/EBC20240044","DOIUrl":"10.1042/EBC20240044","url":null,"abstract":"Malate dehydrogenases (MDHs) have been extensively studied since the 1960s due to their key roles in carbon metabolism and pathways such as redox balance and lipid synthesis. Recently, there has been renewed interest in these enzymes with the discovery of their role in the metabolic changes that occur during cancer and a widespread community of undergraduate teaching laboratories addressing MDH research questions, the Malate Dehydrogenase CUREs Community (MCC). This special issue describes different facets of MDH, including its physiological role, its structure-function relationships, its regulation through post-translational modifications, and perspectives on its evolutionary history. There are two human isoforms: a cytoplasmic isoform that carries out formation of NAD+ for glycolysis, and a mitochondrial isoform that plays a major role in the citric acid cycle. Although the sequences of these two isoforms vary, the structures of the enzymes are similar, and studies suggest that each isoform may form complexes with other enzymes in common pathways. Experimental and theoretical advances have helped to characterize the post-translational modifications of MDH, allowing us to ask more complex questions involving the regulation of the enzyme and substrate promiscuity in the context of cancer. Additionally, there are many unresolved questions on the role of malate dehydrogenase in other organisms, especially in parasites. The review articles in this issue seek to shed light on the latest advances in our understanding of MDH and highlight areas for future studies.","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":"68 2","pages":"53-55"},"PeriodicalIF":5.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Insights into the regulation of malate dehydrogenase: inhibitors, activators, and allosteric modulation by small molecules. 洞察苹果酸脱氢酶的调控：抑制剂、激活剂和小分子异构调控。

IF 5.6 2区生物学

Essays in biochemistry Pub Date : 2024-10-03 DOI: 10.1042/EBC20230087

Betsy M Martinez-Vaz, Alicia L Howard, Varuni K Jamburuthugoda, Kevin P Callahan

{"title":"Insights into the regulation of malate dehydrogenase: inhibitors, activators, and allosteric modulation by small molecules.","authors":"Betsy M Martinez-Vaz, Alicia L Howard, Varuni K Jamburuthugoda, Kevin P Callahan","doi":"10.1042/EBC20230087","DOIUrl":"10.1042/EBC20230087","url":null,"abstract":"Cellular metabolism comprises a complex network of biochemical anabolic and catabolic processes that fuel the growth and survival of living organisms. The enzyme malate dehydrogenase (MDH) is most known for its role in oxidizing malate to oxaloacetate (OAA) in the last step of the tricarboxylic acid (TCA) cycle, but it also participates in the malate-aspartate shuttle in the mitochondria as well as the glyoxylate cycle in plants. These pathways and the specific reactions within them are dynamic and must be carefully calibrated to ensure a balance between nutrient/energy supply and demand. MDH structural and functional complexity requires a variety of regulatory mechanisms, including allosteric regulation, feedback, and competitive inhibition, which are often dependent on whether the enzyme is catalyzing its forward or reverse reaction. Given the role of MDH in central metabolism and its potential as a target for therapeutics in both cancer and infectious diseases, there is a need to better understand its regulation. The involvement of MDH in multiple pathways makes it challenging to identify which effectors are critical to its activity. Many of the in vitro experiments examining MDH regulation were done decades ago, and though allosteric sites have been proposed, none to date have been specifically mapped. This review aims to provide an overview of the current knowledge surrounding MDH regulation by its substrate, products, and other intermediates of the TCA cycle while highlighting all the gaps in our understanding of its regulatory mechanisms.","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":" ","pages":"173-181"},"PeriodicalIF":5.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0