Phosphorylation of Phosphofructokinase — The Possible Role of Covalent Modification in the Regulation of Glycolysis
Rivka Beitner in Regulation of Carbohydrate Metabolism, 1985
Fructose-2,6-bisphosphate was shown to be formed by the action of an enzyme called fructose-6-phosphate-2-kinase96 or phosphofructokinase-295 in order to distinguish this enzyme from the phosphofructokinase acting in the glycolytic pathway. Fructose-6-phosphate-2-kinase was effectively inactivated by the administration of glucagon or epinephrine.96,148 It was also inhibited in vitro by the action of the catalytic subunit of cAMP-dependent protein kinase in the presence of ATP. In contrast to the phosphofructokinase acting in glycolysis, phosphorylation of fructose-6-phosphate-2-kinase caused an effective down-regulation of enzyme activity. There was also evidence for the activation of fructose-2,6-bisphosphatase by phosphorylation,96 and it was concluded that the levels of fructose-2,6-bisphosphate in tissue can be effectively regulated by phosphorylation-dephosphorylation mechanisms.96 In combination with a decreased affinity of the phosphorylated phosphofructokinase for fructose-2,6-bisphosphate these mechanisms could provide an efficient regulation of one of the key points of carbohydrate metabolism in liver.
Entamoeba histolytica
Peter D. Walzer, Robert M. Genta in Parasitic Infections in the Compromised Host, 2020
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).
Abnormal Red Cell Metabolism
Harold R. Schumacher, William A. Rock, Sanford A. Stass in Handbook of Hematologic Pathology, 2019
Glucosephosphate isomerase (GPI) catalyzes the conversion of glucose 6-phosphate to fructose 6-phosphate. GPI-deficient cells accumulate glucose 6-phosphate and are deficient in ATP and 2′3-DPG. GPI deficiency, although rare, is the third most common red cell enzymopathy after G6PD deficiency and PK deficiency (2). The structural gene is located on chromosome 19. GPI deficiency is inherited as an autosomal recessive. Homozygotes for GPI deficiency show variable degrees of anemia, while heterozygotes are generally asymptomatic. Anemia is non-spherocytic, with marked polychromasia and reticulocytosis. Hemolytic crises may occur during an episode of infection. The spleen is frequently enlarged. Osmotic fragility is normal. Autohemolysis test shows increased hemolysis at 48 hr, and is partially corrected by glucose and ATP (type I pattern). A fluorescent test is available for screening the deficiency, and the diagnosis is established on quantitative assay of the enzyme (2). Patients with a severe form of disease may require repeated transfusions. Splenectomy is not curative, but reduces transfusion requirement (2).
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).
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].
Is air pollution a potential cause of neuronal injury?
Published in Neurological Research, 2019
Yu Ji, Christopher Stone, Longfei Guan, Changya Peng, Wei Han
As it occurs in the periphery, the purpose of gluconeogenesis may be described generally as, along with glycogenolysis, the maintenance of energy homeostasis through the generation of glucose for use by extrahepatic tissues during prolonged fasts, a task it achieves through de novo synthesis of glucose from precursors such as glycerol, amino acids, pyruvate, and lactate [31]. Accomplishing this requires the coordinated function of a series of enzyme-catalyzed reactions, most of which are also involved in glycolysis, and simply run in reverse while serving the anabolic purpose of gluconeogenesis. In addition to these reversible steps, however, gluconeogenesis possesses several unique, irreversible enzymes that serve as important regulatory checkpoints in the coordination of cellular energy metabolism with overall organismal energy homeostasis: pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), fructose 1,6-bisphosphatase (FBP), and glucose 6-phosphatase (G6PC) [32]. PC catalyzes the ATP-intensive first of these regulatory reactions within mitochondria by carboxylating pyruvate to yield oxaloacetate. Oxaloacetate is subsequently decarboxylated, shuttled out of the mitochondrion, and then phosphorylated by PEPCK in a reaction that requires GTP. After an intervening sequence of reversed glycolysis reactions that generates fructose 1,6-bisphosphate, FBP yields fructose 6-phosphate, which is isomerized to glucose 6-phosphate and, finally, dephosphorylated to yield glucose de novo; these latter two dephosphorylations both require ATP.
Related Knowledge Centers
- Fructokinase
- Fructose
- Glucose
- Metabolic Pathway
- Phosphorylation
- Fructosephosphates
- Cell
- Fructose 1-Phosphate
- Fructose 2,6-Bisphosphate
- Glycolysis