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Entamoeba histolytica
Published in Peter D. Walzer, Robert M. Genta, Parasitic Infections in the Compromised Host, 2020
William A. Petri, Jonathan I. Ravdin
The biochemistry of E. histolytica has recently been reviewed (80), The end products of carbohydrate metabolism are ethanol and carbon dioxide when the organism is growing anaerobically; acetate is also formed in the presence of oxygen (80). Glucose uptake by trophozoites is via a specific receptor; uptake via this receptor is several orders of magnitude greater than glucose uptake via pinocytosis and is the rate-limiting step in glycolysis (81). The conversion of fructose-6-phosphate to fructose-1,6-diphosphate is via a unique enzyme that utilizes inorganic pyrophosphate (82). Amebas do not contain mitochondria or cytochromes; however, ferredoxin-like iron-containing proteins are present and are likely involved in electron transport (83). Entamoeba histolytica has been the only eukaryote found not to produce the enzymes of glutathione metabolism (84). Hydrolyzed nucleic acids promote the in vitro growth of E. histolytica. The organism is incapable of de novo purine nucleotide synthesis (85); it is not known if amebas can synthesize pyrimidine nucleotides or if salvage pathways exist (80,85).
Fructose-1,6-diphosphatase deficiency
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
The enzyme FDP (EC 3.1.3.11) provides an essential step in the pathway of gluconeogenesis (Figure 49.1). The enzyme catalyzes the irreversible conversion of fructose-1,6-diphosphate to fructose-6-phosphate. Another enzyme, phosphofructokinase, and adenosine triphosphate (ATP) are required to take this reaction in the reverse direction. The enzyme is most active in liver and kidney; and the liver enzyme is highly regulated [4]. Deficiency has most often been documented in the biopsied liver. The gene (FBP1) has been cloned and localized to chromosome 9q22.2-22.3 [5]. Seven exons span 31 kb. The common mutation in Japanese people is an insertion, 960–961insG [6], which was also the most frequent mutation in a non-Japanese population [7, 8]. This mutation causes a frameshift and premature chain termination, as does 966del, and expression studies have shown both to be pathogenic. The disease is clearly genetically heterogeneous and a variety of other mutations has been found.
The Bioenergetics of Mammalian Sperm Motility
Published in Claude Gagnon, Controls of Sperm Motility, 2020
In many tissues, glucose 6-phosphate and fructose 1,6-bisphosphate can be hydrolyzed to glucose or fructose 6-phosphate by glucose 6-phosphatase and fructose 1,6-bisphosphatase, respectively. These reactions are integral to gluconeogenesis, but because they occur alongside the corresponding kinase reactions, they permit substrate cycling driven by the conversion of ATP to ADP and Pi (Figure 6). This is often referred to as futile substrate cycling because it consumes ATP to no apparent purpose, but it may have useful physiological roles, e.g., heat production or increasing the sensitivity of metabolic regulation.134,135
Advances in oxidative stress in pathogenesis of diabetic kidney disease and efficacy of TCM intervention
Published in Renal Failure, 2023
Xiaoju Ma, Jingru Ma, Tian Leng, Zhongzhu Yuan, Tingting Hu, Qiuyan Liu, Tao Shen
In the glycolysis pathway, approximately 2–5% glucose-6-phosphate (G6P) is converted to fructose-6-phosphate (F6P) and then enters the hexosamine pathway [13]. At states of sustained hyperglycemia, excessive F6P is converted to glucosamine-6-phosphate (GlcN6P) under the catalysis of glutamine fructose-6-phosphate aminotransferase (GFAT), followed by generation of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) with the action of related enzymes. The UDP-GlcNAc is then used as substrate for O-linked N-acetylglucosamine (O-GlcNAc) glycosylation under the catalysis of O-GlcNAc transferase. It was reported that hexosamine can induce endoplasmic reticulum (ER) stress in endothelial cells and macrophages, leading to increased oxidative stress responses. Another study revealed that overexpression of GFAT increases NF-κB promoter activity and TNF-α expression in mesangial cells and stimulates the production of TGF-β1 and PAI-1, inducing inflammatory response, extracellular matrix (ECM) accumulation and diabetic glomerulosclerosis [14].
PFKFB3 downregulation aggravates Angiotensin II-induced podocyte detachment
Published in Renal Failure, 2023
Xiaoxiao Huang, Zhaowei Chen, Zilv Luo, Yiqun Hao, Jun Feng, Zijing Zhu, Xueyan Yang, Zongwei Zhang, Jijia Hu, Wei Liang, Guohua Ding
The homodimeric and bifunctional enzyme family of phosphofructokinase-2/Fructose-2,6-bisphosphatase (PFK-2/PFKFB) promotes glycolysis by increasing levels of fructose-2,6-bisphosphate (F2,6P2), which in turn activates the key rate-limiting enzyme 6-phosphofructo-1-kinase (PFK-1) and enhances the conversion of fructose-6-phosphate (F6P) to fructose-1,6-bisphosphate (F1,6P2) in the glycolytic pathway. This causes increased glycolytic flux and increased ATP and NADH production [16]. Among the PFKFB family of four enzymes (PFKFB1-4), PFKFB3 has the highest ratio of kinase to phosphatase activity, which ensures a high glycolytic rate [17]. Recent findings have indicated that PFKFB3 exerts protective effects on the kidneys [18] and promotes the activation of cyclin-dependent kinase-1(cdk1) [19], which promotes talin1 phosphorylation [20]. Excessive talin1 phosphorylation promotes integrin beta1 subunit (ITGB1) activity on the cell surface [21]. Active ITGB1 is an important adhesion molecule on the surface of podocytes, and its activation enhances podocyte adhesion capacity [22–25]. Inhibiting PFKFB3 significantly reduces the expression of cell adhesion molecules, resulting in diminished cell adhesion [26–29]. Therefore, we speculated that Ang II could inhibit talin1 phosphorylation and ITGB1 activation through downregulating PFKFB3 expression. Therefore, we investigated the role of PFKFB3 in Ang II-induced podocyte injury and identified a novel target for CKD treatment.
Glycometabolic rearrangements–aerobic glycolysis in pancreatic ductal adenocarcinoma (PDAC): roles, regulatory networks, and therapeutic potential
Published in Expert Opinion on Therapeutic Targets, 2021
Enhanced glycolysis is well known to be closely associated with resistance to tumor therapy [83]. Many studies have demonstrated a link between enhanced glycolysis and therapy resistance in a variety of cancers, including PDAC [84–87]. Enhanced glycolysis in PDAC was shown to promote resistance to gemcitabine, whereas the application of 2DG, an inhibitor of glycolysis, reversed this effect [87]. According to the published studies, the mechanisms by which aerobic glycolysis influences therapy sensitivity of PDAC can be summarized as follows. (1) HK2, a key enzyme of glycolysis, is induced to dimerize and combine with voltage‐dependent anion channels by ROS derived from gemcitabine, leading to resistance to gemcitabine [88]. (2) Fructose-1,6-bisphosphatase (FBP1), a key enzyme in gluconeogenesis, helps to convert fructose-1,6-bisphosphate to fructose-6-phosphate [18]. Loss of FBP1 in PDAC activates the IQGAP1–extracellular regulatory protein kinase (ERK)–Myc axis, causing resistance to gemcitabine [89]. (3) Upregulation of mucin-1 (MUC1), an oncogene in various cancers and a contributor to glycometabolic rearrangements in PDAC, promotes glycolysis, the pentose phosphate pathway, and nucleotide biosynthesis pathways [90]. Thus, DNA damage repair is enhanced, facilitating resistance to radiotherapy [91].