Essays in biochemistry最新文献_第2页

Considerations for prioritising clinical research using bacteriophage. 利用噬菌体进行临床研究的优先考虑因素。

IF 5.6 2区生物学

Essays in biochemistry Pub Date : 2024-10-30 DOI: 10.1042/EBC20240013

Sarah J L Edwards, Yiran Tao, Rodas Elias, Robert Schooley

{"title":"Considerations for prioritising clinical research using bacteriophage.","authors":"Sarah J L Edwards, Yiran Tao, Rodas Elias, Robert Schooley","doi":"10.1042/EBC20240013","DOIUrl":"https://doi.org/10.1042/EBC20240013","url":null,"abstract":"Antimicrobial resistance (AMR) poses a significant global health threat, as it contributes to prolonged illness, higher mortality rates and increased healthcare costs. As traditional antibiotics become less effective, treatments such as bacteriophage therapy offer potential solutions. The question remains, however, on how to set research priorities in the face of a growing number of antibiotic-resistant pathogens, some common and/or dangerous. One standard way of making decisions about which research to prioritise is by using the disability-adjusted life year metric to estimate the current global impact of a disease or condition, combined with considerations of social justice although decisions made at a national level by governments, especially in low income countries with forecasting potential over future needs may look very different. Another approach is based on the needs of researchers and regulators given what we know about the technology itself. The biological characteristics of bacteriophage therapies set challenges to a universal and standardised prioritisation method. A proof of principle is still arguably needed. With a preliminary discussion of the scope and complexity of AMR and AMR therapeutics, we propose some implications of regulatory frameworks aiming to integrate bacteriophage therapy into mainstream medical practice while gathering scientific data on safety and efficacy, enhancing the collective action needed to combat AMR.","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544460","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

Translational research priorities for bacteriophage therapeutics. 噬菌体疗法的转化研究重点。

IF 5.6 2区生物学

Essays in biochemistry Pub Date : 2024-10-17 DOI: 10.1042/EBC20240020

Robert T Schooley

{"title":"Translational research priorities for bacteriophage therapeutics.","authors":"Robert T Schooley","doi":"10.1042/EBC20240020","DOIUrl":"https://doi.org/10.1042/EBC20240020","url":null,"abstract":"The growing threat of antimicrobial resistant (AMR) bacterial pathogens coupled with the relative dearth of promising novel antibiotics requires the discovery and development additional medical interventions. Over the past decade bacteriophages have emerged one of the most promising new tools to combat AMR pathogens. Anecdotal clinical experiences under so-called 'compassionate use' regulatory pathways as well as a limited number of clinical trials have provided ample evidence of safety and early evidence of efficacy. For phages to reach their full potential it is critical that rigorous clinical trials be conducted that define their optimal use and that enable regulatory authorities to support the commercialization required to afford global access. The clinical development of phage therapeutics requires the design and execution of clinical trials that take full advantage of lessons learned from a century of antibiotic development and that use clinical investigation as a platform in which aspects of phage biology that are critical to therapeutics are more clearly elucidated. Translational research that elucidates phage biology in the context of clinical trials will promote highly relevant hypothesis-driven work in basic science laboratories and will greatly accelerate the development of the field of phage therapeutics.","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460914","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

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