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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
Deficiency of fructose-1,6-diphosphatase (FDP) (fructose-1,6-bisphosphatase) was first recognized in 1970 by Baker and Winegrad [1], in a girl with hypoglycemia and metabolic acidosis. A sibling had died of a similar illness. In subsequent reports in 1971 by Baerlocher and colleagues [2] and by Hulsmann and Fernandez [3], there were multiple affected siblings of consanguineous matings.
The Bioenergetics of Mammalian Sperm Motility
Published in Claude Gagnon, Controls of Sperm Motility, 2020
Recently, it has been demonstrated that bovine sperm phosphofructokinase is strongly activated by the effector fructose 2,6-bisphosphate.130 The enzyme was weakly stimulated by AMP and was unresponsible to glucose 1,6-bisphosphate relative to the muscle enzyme, but was very responsive to fructose 2,6-bisphosphate with 10 μM producing a maximum response. Fructose 2,6-bisphosphate and AMP also inhibited fructose 1,6-bisphosphatase. Sperm contained about 12 μM fructose 2,6-bisphosphate, but the concentration was unresponsive to inhibitors or stimulators of glycolytic flux. Nevertheless, it may explain the high degree of activation of phosphofructokinase generally observed in sperm.131
Metabolic Diseases
Published in Stephan Strobel, Lewis Spitz, Stephen D. Marks, Great Ormond Street Handbook of Paediatrics, 2019
Stephanie Grünewald, Alex Broomfield, Callum Wilson
Fructose 1, 6 bisphosphatase is a key enzyme in the gluceoneogenic pathway, with deficiency impairing the production of glucose from all gluconeogenic precursors including fructose. Children with fructose 1, 6-bisphosphatase deficiency have a greater tolerance to fructose than those with hereditary fructose intolerance as they can still metabolise fructose 1-P to lactate.
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].
Research progress of nanocarriers for gene therapy targeting abnormal glucose and lipid metabolism in tumors
Published in Drug Delivery, 2021
Xianhu Zeng, Zhipeng Li, Chunrong Zhu, Lisa Xu, Yong Sun, Shangcong Han
Gluconeogenesis can generate free glucose from non-carbohydrate carbon substrates (such as glycerol, lactic acid, pyruvate, and glycogenic amino acids). Although it is less studied than catabolic glycolysis or oxidative phosphorylation (OXPHOS), this anabolic pathway plays the same role in controlling the aerobic glycolysis of cancer cells (Seenappa et al. 2016). The complete pathway consists of 11 enzyme-catalyzed reactions, of which there are 7 reactions that are the opposite steps of glycolysis, and 3 reactions that are not involved in gluconeogenesis: (i) the conversion of pyruvate to phosphoenolpyruvate, which is determined by the reaction that catalyzes pyruvate carboxylase (PC) and phosphoenolpyruvate carboxykinase (PEPCK); (ii) the catalyzation of the conversion of fructose-1,6-diphosphate to fructose-6-phosphate by fructose-1,6-bisphosphatase (FBPase); (iii) the catalyzation of the conversion of glucose-6-phosphate to glucose by glucose-6-phosphatase (G6Pase) (Icard et al. 2019). PEPCK, FBPase, and G6Pase are the key enzymes that control the gluconeogenesis flux, thereby affecting glycolysis, the TCA cycle, the PPP and other branched metabolic pathways (serine biosynthesis, glycogen health, gluconeogenesis, and glutamine decomposition) (Kang et al. 2016; Icard et al. 2019).
Genetic Analysis of Tyrosinemia Type 1 and Fructose-1, 6 Bisphosphatase Deficiency Affected in Pakistani Cohorts
Published in Fetal and Pediatric Pathology, 2020
Muhammad Yasir Zahoor, Huma Arshad Cheema, Sadaqat Ijaz, Zafar Fayyaz
Fructose 1,6 bisphosphatase deficiency (FBPD) is an autosomal recessive disorder caused by deficiency or absence of the fructose 1,6 bisphosphatase (FBPase) enzyme that converts fructose-1,6-bisphosphate (FBP) to fructose-6-phosphate (F-6-P) and inorganic phosphate, a critical step in gluconeogenesis. FBPase is encoded by the FBP1 gene, located at chromosome 9q22.3, which comprises eight exons and spans over 31 kb of DNA [7–9]. To date about 50 mutations causing FBPD have been reported in FBP1. Seventeen of these are missense mutations, one is a splicing defect, ten are small deletions, six are gross deletions, five are small insertions, and one is a small indel [10]. We have previously reported three mutations in FAH in three HT1 families [11] and three mutations of FBP1 in nine FBPD affected families [12]. We now report mutational analysis of FAH and FBP1 in four new tyrosinemia type 1 and eight new FBPD families, respectively.