REGULATORY MECHANISMS
David M. Gibson, Robert A. Harris in Metabolic Regulation in Mammals, 2001
The levels of a few metabolic intermediates rise in concentration in response to insulin signaling. One of these, fructose 2,6-bisphosphate, stimulates glycolysis in liver at the step in which fructose 6-phosphate is converted to fructose 1,6-bisphosphate, by binding to the enzyme 6-phosphofructo-1 kinase (Figure 8.2, Chapter 8). Crucial for the opposite How toward gluconeogenesis, fructose 1,6-bisphosphatase is inhibited by the allostcric binding ol the same fructose 2,6-bisphosphate. This allostcriceffector, w hich is not on the mainline glycolytic flow, is created through insulin action in liver following feeding and diminished by glucagon signaling in starvation. The synthesis of fructose 2,6-bisphosphate is catalyzed by a kinase (acting on fructose 6-phosphate) which is active in the dcphosphorylated state and thus fits into the pattern of the insulin-cued "dephosphorylation set". In the same circumstance dephosphorylation (by insulin) of the opposing fructose 2,6-bisphosphatase blocks its activity. Interestingly these competing activities, catalyzed by distinct active sites, are domains of a single polypeptide, a "(»¡functional enzvme" (Figure 8.S, Chapter 8). Insulin-signaled dephosphorylation of the enzyme affects both the (increased) kinase and (decreased) phosphatase directions. Glucagon, through PKA protein phosphorylation of the bifunctional enzyme, switches the whole operation around, thereby promoting gluconeogenesis. A similar but distinctive system operates in skeletal and cardiac muscles (Chapter 6).
Anaerobic endurance: the speed endurance sports
Nick Draper, Helen Marshall in Exercise Physiology, 2014
At the fourth step of glycolysis the enzyme aldolase catalyses the splitting of fructose-1,6-bisphosphate (a hexose, 6 carbon ring) into two triose (three carbon chain) molecules, dihydroxyacetone phosphate and glyceraldehyde-3-phosphate (G3P), each of which contains one of the phosphate groups. Catalysed by triose phosphate isomerase, dihydroxyacetone phosphate is then restructured in the fifth step of glycolysis to form another glyceraldehyde-3-phosphate. This reaction is necessary because only glyceraldehyde-3-phosphate can participate in the subsequent reactions of glycolysis. At this point the newly created glyceraldehyde-3-phosphate molecule can pass, along with the original glyceraldehyde-3-phosphate molecule, to the sixth step of glycolysis. From this point on, therefore, there are two molecules of each metabolite, derived from the original single glucose molecule.
Fish Allergy
Andreas L. Lopata in Food Allergy, 2017
Enolases and aldolases are key enzymes of the catabolic glycolysis present in all tissues. Aldolase or 40 kDa-fructose-bisphosphate aldolase (EC 4.1.2.13) splits fructose 1,6-bisphosphate into triose phosphates dihydroxyacetone phosphate and glyceraldehyde 3-phosphate (4th step of glycolysis) (Garfinkel and Garfinkel 1985). Enolase or 50 kDa-phosphopyruvate hydratase (EC 4.2.1.11) is a metalloenzyme (Mg2+-ions per molecule) catalysing the conversion of 2-phosphoglycerate to phosphoenolpyruvate (9th step of glycolysis). Both enzymes belong to the structural family of so-called “TIM barrel”-proteins (Kuehn et al. 2016). Eponym for this family is the triosephosphate isomerase (TIM), which was characterized as the first protein by a common structure of eight alpha-helices alternating with eight beta-strands. Despite of the structural homology within this family, there is a lack of substantial sequence identity between TIM barrel-proteins.
Interaction of low frequency external electric fields and pancreatic β-cell: a mathematical modeling approach to identify the influence of excitation parameters
Published in International Journal of Radiation Biology, 2018
Sajjad Farashi, Pezhman Sasanpour, Hashem Rafii-Tabar
The glycolysis pathway contains a series of reactions for converting glucose into pyruvate and ATP. In the first step glucose is phosphorylated and converted to glucose-6-phosphate (G6P) which will be isomerised to the fructose-6-phosphate (F6P). The further phosphorylation of F6P by phosphofructokinase-1 enzyme produces fructose 1,6-bisphosphate, which in the next step will be cleaved into glyceraldehyde-3-phosphate (G3P) and dihydroxy acetone phosphate (DHAP) using aldolase enzyme. The DHAP is converted to further G3P by triose-phosphate isomerase. This phase, the procedure is preparatory phase and requires energy consumption. In the next step G3P oxidized to 1,3-bisphosphoglycerate incorporating glyceraldehyde 3-phosphate dehydrogenase. A large amount of energy during the oxidation of an aldehyde group will be released. In this step Nicotinamide adenine dinucleotide (NAD+) will be reduced to NADH, the reduced form of NAD+. The enzyme phosphoglycerate kinase transfers the phosphoryl group of 1,3-bisphosphoglycerate to ADP and producing ATP and 3-phosphoglycerate which the latter will be isomerized to 2-phosphoglycerate using Phosphoglycerate mutase. Using the enzyme enolase, 2-phosphoglycerate will be converted to phosphoenolpyruvate (PEP). Finally, PEP will be converted to pyruvate by pyruvate kinase. In this step one extra ATP molecule will be produced. The glycolysis pathway is depicted in Figure 1.
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.
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].
Related Knowledge Centers
- Fructose
- Glucose
- Metabolic Pathway
- Phosphorylation
- Glycolysis
- Fructosephosphates
- Cell
- Fructose 6-Phosphate
- Glyceraldehyde 3-Phosphate
- Dihydroxyacetone Phosphate