Essays in biochemistry最新文献

{"title":"Chemical approaches to the sulfation of small molecules: current progress and future directions.","authors":"Jaber A Alshehri, Alan M Jones","doi":"10.1042/EBC20240001","DOIUrl":"10.1042/EBC20240001","url":null,"abstract":"<p><p>Sulfation is one of the most important modifications that occur to a wide range of bioactive small molecules including polysaccharides, proteins, flavonoids, and steroids. In turn, these sulfated molecules have significant biological and pharmacological roles in diverse processes including cell signalling, modulation of immune and inflammation response, anti-coagulation, anti-atherosclerosis, and anti-adhesive properties. This Essay summarises the most encountered chemical sulfation methods of small molecules. Sulfation reactions using sulfur trioxide amine/amide complexes are the most used method for alcohol and phenol groups in carbohydrates, steroids, proteins, and related scaffolds. Despite the effectiveness of these methods, they suffer from issues including multiple-purification steps, toxicity issues (e.g., pyridine contamination), purification challenges, stoichiometric excess of reagents which leads to an increase in reaction cost, and intrinsic stability issues of both the reagent and product. Recent advances including SuFEx, the in situ reagent approach, and TBSAB show the widespread appeal of novel sulfating approaches that will enable a larger exploration of the field in the years to come by simplifying the purification and isolation process to access bespoke sulfated small molecules.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":" ","pages":"449-466"},"PeriodicalIF":5.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491365","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}

{"title":"Genetic variability in proteoglycan biosynthetic genes reveals new facets of heparan sulfate diversity.","authors":"Mohand Ouidir Ouidja, Denis S F Biard, Minh Bao Huynh, Xavier Laffray, Wilton Gomez-Henao, Sandrine Chantepie, Gael Le Douaron, Nicolas Rebergue, Auriane Maïza, Heloise Merrick, Aubert De Lichy, Alwyn Dady, Oscar González-Velasco, Karla Rubio, Guillermo Barreto, Kévin Baranger, Valerie Cormier-Daire, Javier De Las Rivas, David G Fernig, Dulce Papy-Garcia","doi":"10.1042/EBC20240106","DOIUrl":"10.1042/EBC20240106","url":null,"abstract":"<p><p>Heparan sulfate (HS) and chondroitin sulfate (CS) proteoglycans (PG) consist of a core protein to which the glycosaminoglycan (GAG) chains, HS or CS, are attached through a common linker tetrasaccharide. In the extracellular space, they are involved in the regulation of cell communication, assuring development and homeostasis. The HSPG biosynthetic pathway has documented 51 genes, with many diseases associated to defects in some of them. The phenotypic consequences of this genetic variation in humans, and of genetic ablation in mice, and their expression patterns, led to a phenotypically centered HSPG biosynthetic pathway model. In this model, HS sequences produced by ubiquitous NDST1, HS2ST and HS6ST enzymes are essential for normal development and homeostasis, whereas tissue restricted HS sequences produced by the non-ubiquitous NDST2-4, HS6ST2-3, and HS3ST1-6 enzymes are involved in adaptative behaviors, cognition, tissue responsiveness to stimuli, and vulnerability to disease. The model indicates that the flux through the HSPG/CSPG pathways and its diverse branches is regulated by substrate preferences and protein-protein-interactions. This results in a privileged biosynthesis of HSPG over that of CSPGs, explaining the phenotypes of linkeropathies, disease caused by defects in genes involved in the biosynthesis of the common tetrasaccharide linker. Documented feedback loops whereby cells regulate HS sulfation, and hence the interactions of HS with protein partners, may be similarly implemented, e.g., protein tyrosine sulfation and other posttranslational modifications in enzymes of the HSPG pathway. Together, ubiquitous HS, specialized HS, and their biosynthesis model can facilitate research for a better understanding of HSPG roles in physiology and pathology.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":"68 4","pages":"555-578"},"PeriodicalIF":5.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767438","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}

{"title":"Polysaccharide sulfotransferases: the identification of putative sequences and respective functional characterisation.","authors":"Ravina Mistry, Dominic P Byrne, David Starns, Igor L Barsukov, Edwin A Yates, David G Fernig","doi":"10.1042/EBC20230094","DOIUrl":"10.1042/EBC20230094","url":null,"abstract":"<p><p>The vast structural diversity of sulfated polysaccharides demands an equally diverse array of enzymes known as polysaccharide sulfotransferases (PSTs). PSTs are present across all kingdoms of life, including algae, fungi and archaea, and their sulfation pathways are relatively unexplored. Sulfated polysaccharides possess anti-inflammatory, anticoagulant and anti-cancer properties and have great therapeutic potential. Current identification of PSTs using Pfam has been predominantly focused on the identification of glycosaminoglycan (GAG) sulfotransferases because of their pivotal roles in cell communication, extracellular matrix formation and coagulation. As a result, our knowledge of non-GAG PSTs structure and function remains limited. The major sulfotransferase families, Sulfotransfer_1 and Sulfotransfer_2, display broad homology and should enable the capture of a wide assortment of sulfotransferases but are limited in non-GAG PST sequence annotation. In addition, sequence annotation is further restricted by the paucity of biochemical analyses of PSTs. There are now high-throughput and robust assays for sulfotransferases such as colorimetric PAPS (3'-phosphoadenosine 5'-phosphosulfate) coupled assays, Europium-based fluorescent probes for ratiometric PAP (3'-phosphoadenosine-5'-phosphate) detection, and NMR methods for activity and product analysis. These techniques provide real-time and direct measurements to enhance the functional annotation and subsequent analysis of sulfated polysaccharides across the tree of life to improve putative PST identification and characterisation of function. Improved annotation and biochemical analysis of PST sequences will enhance the utility of PSTs across biomedical and biotechnological sectors.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":" ","pages":"431-447"},"PeriodicalIF":5.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862484","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}

{"title":"Steroid metabolism and hormonal dynamics in normal and malignant ovaries.","authors":"Lucy I Beevors, Sudha Sundar, Paul A Foster","doi":"10.1042/EBC20240028","DOIUrl":"10.1042/EBC20240028","url":null,"abstract":"<p><p>The ovaries are key steroid hormone production sites in post-pubertal females. However, current research on steroidogenic enzymes, endogenous hormone concentrations and their effects on healthy ovarian function and malignant development is limited. Here, we discuss the importance of steroid enzymes in normal and malignant ovaries, alongside hormone concentrations, receptor expression and action. Key enzymes include STS, 3β-HSD2, HSD17B1, ARK1C3, and aromatase, which influence ovarian steroidal action. Both androgen and oestrogen action, via their facilitating enzyme, drives ovarian follicle activation, development and maturation in healthy ovarian tissue. In ovarian cancer, some data suggest STS and oestrogen receptor α may be linked to aggressive forms, while various oestrogen-responsive factors may be involved in ovarian cancer metastasis. In contrast, androgen receptor expression and action vary across ovarian cancer subtypes. For future studies investigating steroidogenesis and steroidal activity in ovarian cancer, it is necessary to differentiate between disease subtypes for a comprehensive understanding.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":" ","pages":"491-507"},"PeriodicalIF":5.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589988","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}

{"title":"Analytical methods for quantitating sulfate in plasma and serum.","authors":"Prasidhee Vijayakumar, Paul A Dawson","doi":"10.1042/EBC20230092","DOIUrl":"10.1042/EBC20230092","url":null,"abstract":"<p><p>Circulating sulfate needs to be maintained at sufficiently high levels for healthy growth and development. Animal studies have shown the adverse physiological consequences of low circulating sulfate level on the skeletal, neurological and reproductive systems. However, sulfate is not routinely measured in clinical investigations, despite the importance of sulfate being documented over the past several decades. Several methods have been developed for measuring serum and plasma sulfate level in animals and humans, including a range of barium sulfate precipitation techniques that have been a major focus of sulfate analytics since the 1960s. Evaluation of an ion chromatography method demonstrated its utility for investigation of sulfate levels in human health. More recently, liquid chromatography-tandem mass spectrometry has been used to show hyposulfatemia in a human case of mild skeletal dysplasia. This article provides an overview of analytical methods for measuring sulfate in serum and plasma, highlighting the strengths and limitations of each method.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":" ","pages":"383-389"},"PeriodicalIF":5.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863587","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}

{"title":"Steroid sulfatase and sulfotransferases in the estrogen and androgen action of gynecological cancers: current status and perspectives.","authors":"Tea Lanišnik Rižner, Marija Gjorgoska","doi":"10.1042/EBC20230096","DOIUrl":"10.1042/EBC20230096","url":null,"abstract":"<p><p>Sulfatase (STS) and sulfotransferases (SULT) have important role in the biosynthesis and action of steroid hormones. STS catalyzes the hydrolysis of estrone-sulfate (E1-S) and dehydroepiandrosterone-sulfate (DHEA-S), while sulfotransferases catalyze the reverse reaction and require 3-phosphoadenosine-5-phosphosulfate as a sulfate donor. These enzymes control the concentration of active estrogens and androgens in peripheral tissues. Aberant expression of STS and SULT genes has been found in both, benign hormone-dependent diseases and hormone-dependent cancers. The aim of this review is to present the current knowledge on the role of STS and SULT in gynecological cancers, endometrial (EC) and ovarian cancer (OC). EC is the most common and OC the most lethal gynecological cancer. These cancers primarily affect postmenopausal women and therefore rely on the local production of steroid hormones from inactive precursors, either DHEA-S or E1-S. Following cellular uptake by organic anion transporting polypeptides (OATP) or organic anion transporters (OAT), STS and SULT regulate the formation of active estrogens and androgens, thus disturbed balance between STS and SULT can contribute to the onset and progression of cancer. The importance of these enzymes in peripheral estrogen biosynthesis has long been recognized, and this review provides new data on the important role of STS and SULT in the formation and action of androgens, their regulation and inhibition, and their potential as prognostic biomarkers.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":" ","pages":"411-422"},"PeriodicalIF":5.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589989","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}

{"title":"Sulfation pathways in the maintenance of functional beta-cell mass and implications for diabetes.","authors":"Jonathan Wolf Mueller, Patricia Thomas, Louise Torp Dalgaard, Gabriela da Silva Xavier","doi":"10.1042/EBC20240034","DOIUrl":"10.1042/EBC20240034","url":null,"abstract":"<p><p>Diabetes Type 1 and Type 2 are widely occurring diseases. In spite of a vast amount of biomedical literature about diabetic processes in general, links to certain biological processes are only becoming evident these days. One such area of biology is the sulfation of small molecules, such as steroid hormones or metabolites from the gastrointestinal tract, as well as larger biomolecules, such as proteins and proteoglycans. Thus, modulating the physicochemical propensities of the different sulfate acceptors, resulting in enhanced solubility, expedited circulatory transit, or enhanced macromolecular interaction. This review lists evidence for the involvement of sulfation pathways in the maintenance of functional pancreatic beta-cell mass and the implications for diabetes, grouped into various classes of sulfated biomolecule. Complex heparan sulfates might play a role in the development and maintenance of beta-cells. The sulfolipids sulfatide and sulfo-cholesterol might contribute to beta-cell health. In beta-cells, there are only very few proteins with confirmed sulfation on some tyrosine residues, with the IRS4 molecule being one of them. Sulfated steroid hormones, such as estradiol-sulfate and vitamin-D-sulfate, may facilitate downstream steroid signaling in beta-cells, following de-sulfation. Indoxyl sulfate is a metabolite from the intestine, that causes kidney damage, contributing to diabetic kidney disease. Finally, from a technological perspective, there is heparan sulfate, heparin, and chondroitin sulfate, that all might be involved in next-generation beta-cell transplantation. Sulfation pathways may play a role in pancreatic beta-cells through multiple mechanisms. A more coherent understanding of sulfation pathways in diabetes will facilitate discussion and guide future research.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":" ","pages":"509-522"},"PeriodicalIF":5.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282309","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}

{"title":"Does AMPK bind glycogen in skeletal muscle or is the relationship correlative?","authors":"Barnaby P Frankish, Robyn M Murphy","doi":"10.1042/EBC20240006","DOIUrl":"10.1042/EBC20240006","url":null,"abstract":"<p><p>Since its discovery over five decades ago, an emphasis on better understanding the structure and functional role of AMPK has been prevalent. In that time, the role of AMPK as a heterotrimeric enzyme that senses the energy state of various cell types has been established. Skeletal muscle is a dynamic, plastic tissue that adapts to both functional and metabolic demands of the human body, such as muscle contraction or exercise. With a deliberate focus on AMPK in skeletal muscle, this review places a physiological lens to the association of AMPK and glycogen that has been established biochemically. It discusses that, to date, no in vivo association of AMPK with glycogen has been shown and this is not altered with interventions, either by physiological or biochemical utilisation of glycogen in skeletal muscle. The reason for this is likely due to the persistent phosphorylation of Thr148 in the β-subunit of AMPK which prevents AMPK from binding to carbohydrate domains. This review presents the correlative data that suggests AMPK senses glycogen utilisation through a direct interaction with glycogen, the biochemical data showing that AMPK can bind carbohydrate in vitro, and highlights that in a physiological setting of rodent skeletal muscle, AMPK does not directly bind to glycogen.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":" ","pages":"337-347"},"PeriodicalIF":5.6,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11576187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079730","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}

{"title":"A special issue of Essays in Biochemistry on AMPK and AMPK-related kinases.","authors":"Ian P Salt, David Carling","doi":"10.1042/EBC20240038","DOIUrl":"10.1042/EBC20240038","url":null,"abstract":"<p><p>In eukaryotic cells, AMP-activated protein kinase (AMPK) plays a central role in responding to nutrient limitation by switching-off ATP-consuming (anabolic) pathways and switching-on ATP generating (catabolic) pathways. Over the last 30 years or so, a considerable body of research has been carried out that has provided us with a wealth of knowledge regarding the regulation and role of AMPK. Despite this, there is still much to learn about AMPK and the field remains highly active, with many groups around the world continuing to explore new roles for AMPK, providing insight into its biological function. This review series was inspired by recent AMPK-focused meetings in Scotland (2022) and Australia (2023) and draws on some of the research presented at those meetings.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":"68 3","pages":"269-271"},"PeriodicalIF":5.6,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11576182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647062","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}

{"title":"New developments in AMPK and mTORC1 cross-talk.","authors":"William J Smiles, Ashley J Ovens, Bruce E Kemp, Sandra Galic, Janni Petersen, Jonathan S Oakhill","doi":"10.1042/EBC20240007","DOIUrl":"10.1042/EBC20240007","url":null,"abstract":"<p><p>Metabolic homeostasis and the ability to link energy supply to demand are essential requirements for all living cells to grow and proliferate. Key to metabolic homeostasis in all eukaryotes are AMPK and mTORC1, two kinases that sense nutrient levels and function as counteracting regulators of catabolism (AMPK) and anabolism (mTORC1) to control cell survival, growth and proliferation. Discoveries beginning in the early 2000s revealed that AMPK and mTORC1 communicate, or cross-talk, through direct and indirect phosphorylation events to regulate the activities of each other and their shared protein substrate ULK1, the master initiator of autophagy, thereby allowing cellular metabolism to rapidly adapt to energy and nutritional state. More recent reports describe divergent mechanisms of AMPK/mTORC1 cross-talk and the elaborate means by which AMPK and mTORC1 are activated at the lysosome. Here, we provide a comprehensive overview of current understanding in this exciting area and comment on new evidence showing mTORC1 feedback extends to the level of the AMPK isoform, which is particularly pertinent for some cancers where specific AMPK isoforms are implicated in disease pathogenesis.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":" ","pages":"321-336"},"PeriodicalIF":8.3,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589987","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}