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Carcinogenesis Aug 2023Glucose-6-phosphate dehydrogenase (G6PD) is involved in the catalytic pentose phosphate pathway (PPP), which is closely related to energy metabolism. G6PD plays a...
Glucose-6-phosphate dehydrogenase (G6PD) is involved in the catalytic pentose phosphate pathway (PPP), which is closely related to energy metabolism. G6PD plays a crucial role in many types of cancer, but the specific molecular mechanisms of G6PD in cancer remain unclear. Therefore, we investigated the potential oncogenic role of G6PD in various tumors based on The Cancer Genome Atlas (TCGA), the cBioPortal datasets, the University of California Santa Cruz (UCSC) Xena browser, and the UALCAN-based online tool. G6PD was highly expressed in several cancer tissues (hepatocellular carcinoma, glioma, and breast cancer) compared with normal tissues and was significantly associated with poor prognosis of hepatocellular carcinoma, clear cell renal cell carcinoma, and breast cancer. Promoter methylation levels of G6PD were lower in Bladder Urothelial Carcinoma (BLCA) (P = 2.77e-02), breast invasive carcinoma (BRCA) (P = 1.62e-12), kidney renal clear cell carcinoma (KIRC) (P = 4.23e-02), kidney renal papillary cell carcinoma (KIRP) (P = 2.64e-03), liver hepatocellular carcinoma (LIHC) (P = 1.76e-02), stomach adenocarcinoma (STAD) (P = 3.50e-02), testicular germ cell tumors (TGCT) (P = 1.62e-12), higher in prostate adenocarcinoma (PRAD) (P = 1.81e-09), and uterine corpus endometrial carcinoma (UCEC) (P = 2.96e-04) compared with corresponding normal tissue samples. G6PD expression was positively correlated with the infiltration level of immune cells in most tumors, suggesting that G6PD may be involved in tumor immune infiltration. In addition, the functional mechanism of G6PD also involves 'Carbon metabolism', 'Glycolysis/Gluconeogenesis', 'Pentose phosphate pathway', and 'Central carbon pathway metabolism in cancer signaling pathway'. This pan-cancer study provides a relatively broad understanding of the oncogenic role of G6PD in various tumors and presents a theoretical basis for the development of G6PD inhibitors as therapeutic drugs for multiple cancers.
Topics: Humans; Male; Adenocarcinoma; Breast Neoplasms; Carbon; Carcinogenesis; Carcinoma, Hepatocellular; Carcinoma, Renal Cell; Carcinoma, Transitional Cell; Glucosephosphate Dehydrogenase; Kidney Neoplasms; Liver Neoplasms; Pentoses; Phosphates; Urinary Bladder Neoplasms
PubMed: 37335542
DOI: 10.1093/carcin/bgad043 -
Microbiology and Molecular Biology... Dec 2021Accumulation of phosphorylated intermediates during cellular metabolism can have wide-ranging toxic effects on many organisms, including humans and the pathogens that...
Accumulation of phosphorylated intermediates during cellular metabolism can have wide-ranging toxic effects on many organisms, including humans and the pathogens that infect them. These toxicities can be induced by feeding an upstream metabolite (a sugar, for instance) while simultaneously blocking the appropriate metabolic pathway with either a mutation or an enzyme inhibitor. Here, we survey the toxicities that can arise in the metabolism of glucose, galactose, fructose, fructose-asparagine, glycerol, trehalose, maltose, mannose, mannitol, arabinose, and rhamnose. Select enzymes in these metabolic pathways may serve as novel therapeutic targets. Some are conserved broadly among prokaryotes and eukaryotes (e.g., glucose and galactose) and are therefore unlikely to be viable drug targets. However, others are found only in bacteria (e.g., fructose-asparagine, rhamnose, and arabinose), and one is found in fungi but not in humans (trehalose). We discuss what is known about the mechanisms of toxicity and how resistance is achieved in order to identify the prospects and challenges associated with targeted exploitation of these pervasive metabolic vulnerabilities.
Topics: Arabinose; Galactose; Humans; Lactose; Phosphates; Xylose
PubMed: 34585982
DOI: 10.1128/MMBR.00123-21 -
Carbohydrate Research Dec 2015Xylose is one of the few monosaccharidic building blocks that are used by mammalian cells. In comparison with other monosaccharides, xylose is rather unusual and, so... (Review)
Review
Xylose is one of the few monosaccharidic building blocks that are used by mammalian cells. In comparison with other monosaccharides, xylose is rather unusual and, so far, only found in two different mammalian structures, i.e. in the Notch receptor and as the linker between protein and glycosaminoglycan (GAG) chains in proteoglycans. Interestingly, simple soluble xylopyranosides can not only initiate the biosynthesis of soluble GAG chains but also function as inhibitors of important enzymes in the biosynthesis of proteoglycans. Furthermore, xylose is a major constituent of hemicellulosic xylans and thus one of the most abundant carbohydrates on Earth. Altogether, this has spurred a strong interest in xylose chemistry. The scope of this review is to describe synthesis of xylopyranosyl donors, as well as protective group chemistry, modifications, and conformational analysis of xylose.
Topics: Animals; Glycosides; Humans; Molecular Structure; Pyrans; Xylose
PubMed: 26580709
DOI: 10.1016/j.carres.2015.10.004 -
FEMS Microbiology Reviews Aug 2021Pentose sugars are widespread in nature and two of them, D-xylose and L-arabinose belong to the most abundant sugars being the second and third by abundance sugars in... (Review)
Review
Pentose sugars are widespread in nature and two of them, D-xylose and L-arabinose belong to the most abundant sugars being the second and third by abundance sugars in dry plant biomass (lignocellulose) and in general on planet. Therefore, it is not surprising that metabolism and bioconversion of these pentoses attract much attention. Several different pathways of D-xylose and L-arabinose catabolism in bacteria and yeasts are known. There are even more common and really ubiquitous though not so abundant pentoses, D-ribose and 2-deoxy-D-ribose, the constituents of all living cells. Thus, ribose metabolism is example of endogenous metabolism whereas metabolism of other pentoses, including xylose and L-arabinose, represents examples of the metabolism of foreign exogenous compounds which normally are not constituents of yeast cells. As a rule, pentose degradation by the wild-type strains of microorganisms does not lead to accumulation of high amounts of valuable substances; however, productive strains have been obtained by random selection and metabolic engineering. There are numerous reviews on xylose and (less) L-arabinose metabolism and conversion to high value substances; however, they mostly are devoted to bacteria or the yeast Saccharomyces cerevisiae. This review is devoted to reviewing pentose metabolism and bioconversion mostly in non-conventional yeasts, which naturally metabolize xylose. Pentose metabolism in the recombinant strains of S. cerevisiae is also considered for comparison. The available data on ribose, xylose, L-arabinose transport, metabolism, regulation of these processes, interaction with glucose catabolism and construction of the productive strains of high-value chemicals or pentose (ribose) itself are described. In addition, genome studies of the natural xylose metabolizing yeasts and available tools for their molecular research are reviewed. Metabolism of other pentoses (2-deoxyribose, D-arabinose, lyxose) is briefly reviewed.
Topics: Arabinose; Biofuels; Pentoses; Saccharomyces cerevisiae; Xylose
PubMed: 33316044
DOI: 10.1093/femsre/fuaa069 -
Current Opinion in Biotechnology Feb 2021Biosynthesis of oleochemicals enables sustainable production of natural and unnatural alternatives from renewable feedstocks. Yeast cell factories have been extensively... (Review)
Review
Biosynthesis of oleochemicals enables sustainable production of natural and unnatural alternatives from renewable feedstocks. Yeast cell factories have been extensively studied and engineered to produce a variety of oleochemicals, focusing on both central carbon metabolism and lipid metabolism. Here, we review recent progress towards oleochemical synthesis in yeast based biorefineries, as well as utilization of alternative renewable feedstocks, such as xylose and l-arabinose. We also review recent studies of C1 compound utilization or co-utilization and discuss how these studies can lead to third generation yeast based biorefineries for oleochemical production.
Topics: Carbon; Saccharomyces cerevisiae; Xylose
PubMed: 33360103
DOI: 10.1016/j.copbio.2020.11.009 -
Current Opinion in Biotechnology Jun 2019Energy security, environmental pollution, and economic development drive the development of alternatives to fossil fuels as an urgent global priority. Lignocellulosic... (Review)
Review
Energy security, environmental pollution, and economic development drive the development of alternatives to fossil fuels as an urgent global priority. Lignocellulosic biomass has the potential to contribute to meeting the demand for biofuel production via hydrolysis and fermentation of released sugars, such as glucose, xylose, and arabinose. Construction of robust cell factories requires introducing and rewiring of their metabolism to efficiently use all these sugars. Here, we review recent advances in re-constructing pathways for metabolism of pentoses, with special focus on xylose metabolism in the most widely used cell factories Saccharomyces cerevisiae and Escherichia coli. We also highlight engineering advanced biofuels-synthesis pathways and describes progress toward overcoming the challenges facing adoption of large-scale biofuel production.
Topics: Biofuels; Carbon; Glucose; Hydrolysis; Metabolic Networks and Pathways; Xylose
PubMed: 30785001
DOI: 10.1016/j.copbio.2019.01.006 -
Bioscience Reports Oct 2022Sulfoquinovose (SQ, 6-deoxy-6-sulfo-D-glucose) is a sulfo-sugar with a ubiquitous distribution in the environment due to its production by plants and other... (Review)
Review
Sulfoquinovose (SQ, 6-deoxy-6-sulfo-D-glucose) is a sulfo-sugar with a ubiquitous distribution in the environment due to its production by plants and other photosynthetic organisms. Bacteria play an important role in degradation of SQ and recycling of its constituent sulfur and carbon. Since its discovery in 1963, SQ was noted to have a structural resemblance to glucose-6-phosphate and proposed to be degraded through a pathway analogous to glycolysis, termed sulfoglycolysis. Studies in recent years have uncovered an unexpectedly diverse array of sulfoglycolytic pathways in different bacteria, including one analogous to the Embden-Meyerhof-Parnas pathway (sulfo-EMP), one analogous to the Entner-Doudoroff pathway (sulfo-ED), and two involving sulfo-sugar cleavage by a transaldolase (sulfo-TAL) and transketolase (sulfo-TK), respectively, analogous to reactions in the pentose phosphate (PP) pathway. In addition, a non-sulfoglycolytic SQ degradation pathway was also reported, involving oxygenolytic C-S cleavage catalyzed by a homolog of alkanesulfonate monooxygenase (sulfo-ASMO). Here, we review the discovery of these new mechanisms of SQ degradation and lessons learnt in the study of new catabolic enzymes and pathways in bacteria.
Topics: Transaldolase; Glucose-6-Phosphate; Transketolase; Bacteria; Glycolysis; Sulfur; Glucose; Carbon; Alkanesulfonates; Mixed Function Oxygenases; Phosphates; Pentoses
PubMed: 36196895
DOI: 10.1042/BSR20220314 -
Applied Microbiology and Biotechnology Sep 2018Pentoses represent monosaccharides with five carbon atoms. They are organized into two main groups, aldopentoses and ketopentoses. There are eight aldopentoses and four... (Review)
Review
Pentoses represent monosaccharides with five carbon atoms. They are organized into two main groups, aldopentoses and ketopentoses. There are eight aldopentoses and four ketopentoses and each ketopentose corresponds to two aldopentoses. Only D-xylose, D-ribose, and L-arabinose are natural sugars, but others belong to rare sugars that occur in very small quantities in nature. Recently, rare pentoses attract much attention because of their great potentials for commercial applications, especially as precursors of many important medical drugs. Pentoses Izumoring strategy provides a complete enzymatic approach to link all pentoses using four types of enzymes, including ketose 3-epimerases, aldose-ketose isomerases, polyol dehydrogenases, and aldose reductases. At least 10 types of epimerases and isomerases have been used for biotransformation of all aldopentoses and ketopentoses, and these enzymes are reviewed in detail in this article.
Topics: Aldose-Ketose Isomerases; Biotransformation; Isomerases; Pentoses; Racemases and Epimerases
PubMed: 29968034
DOI: 10.1007/s00253-018-9150-y -
Biotechnology Advances 2023The conventional yeast (Saccharomyces cerevisiae) is the most studied yeast and has been used in many important industrial productions, especially in bioethanol... (Review)
Review
The conventional yeast (Saccharomyces cerevisiae) is the most studied yeast and has been used in many important industrial productions, especially in bioethanol production from first generation feedstock (sugar and starchy biomass). However, for reduced cost and to avoid competition with food, second generation bioethanol, which is produced from lignocellulosic feedstock, is now being investigated. Production of second generation bioethanol involves pre-treatment and hydrolysis of lignocellulosic biomass to sugar monomers containing, amongst others, d-glucose and D-xylose. Intrinsically, S. cerevisiae strains lack the ability to ferment pentose sugars and genetic engineering of S. cerevisiae to inculcate the ability to ferment pentose sugars is ongoing to develop recombinant strains with the required stability and robustness for commercial second generation bioethanol production. Furthermore, pre-treatment of these lignocellulosic wastes leads to the release of inhibitory compounds which adversely affect the growth and fermentation by S. cerevisae. S. cerevisiae also lacks the ability to grow at high temperatures which favour Simultaneous Saccharification and Fermentation of substrates to bioethanol. There is, therefore, a need for robust yeast species which can co-ferment hexose and pentose sugars and can tolerate high temperatures and the inhibitory substances produced during pre-treatment and hydrolysis of lignocellulosic materials. Non-conventional yeast strains are potential solutions to these problems due to their abilities to ferment both hexose and pentose sugars, and tolerate high temperature and stress conditions encountered during ethanol production from lignocellulosic hydrolysate. This review highlights the limitations of the conventional yeast species and the potentials of non-conventional yeast strains in commercialization of second generation bioethanol.
Topics: Saccharomyces cerevisiae; Pentoses; Xylose; Genetic Engineering; Fermentation
PubMed: 36669745
DOI: 10.1016/j.biotechadv.2023.108100 -
Molecular Biology Reports Jan 2024D-ribose, an ubiquitous pentose compound found in all living cells, serves as a vital constituent of numerous essential biomolecules, including RNA, nucleotides, and... (Review)
Review
D-ribose, an ubiquitous pentose compound found in all living cells, serves as a vital constituent of numerous essential biomolecules, including RNA, nucleotides, and riboflavin. It plays a crucial role in various fundamental life processes. Within the cellular milieu, exogenously supplied D-ribose can undergo phosphorylation to yield ribose-5-phosphate (R-5-P). This R-5-P compound serves a dual purpose: it not only contributes to adenosine triphosphate (ATP) production through the nonoxidative phase of the pentose phosphate pathway (PPP) but also participates in nucleotide synthesis. Consequently, D-ribose is employed both as a therapeutic agent for enhancing cardiac function in heart failure patients and as a remedy for post-exercise fatigue. Nevertheless, recent clinical studies have suggested a potential link between D-ribose metabolic disturbances and type 2 diabetes mellitus (T2DM) along with its associated complications. Additionally, certain in vitro experiments have indicated that exogenous D-ribose exposure could trigger apoptosis in specific cell lines. This article comprehensively reviews the current advancements in D-ribose's digestion, absorption, transmembrane transport, intracellular metabolic pathways, impact on cellular behaviour, and elevated levels in diabetes mellitus. It also identifies areas requiring further investigation.
Topics: Humans; Diabetes Mellitus, Type 2; Ribose; Heart Failure; Metabolic Diseases; Adenosine Triphosphate
PubMed: 38281218
DOI: 10.1007/s11033-023-09076-y