Disease relevance of Glycolysis

• In suspensions of Escherichia coli both phosphorus-31 and carbon-13 NMR studies of glycolysis and bioenergetics are presented [1].
• The reduction of glycolysis by hypoglycemia or the glucose analog 2-deoxy-D-glucose (2DG) stimulates compensatory sympathetic alterations of metabolism [2].
• Sepsis is frequently characterized by a number of metabolic abnormalities: increased plasma lactate concentration, metabolic acidosis, increased glycolysis, and an abnormal "delivery-dependent" oxygen consumption [3].
• During low-flow ischemia and postischemic reperfusion in vitro, KD hearts failed to augment glucose uptake and glycolysis, although glucose transporter content and insulin-stimulated glucose uptake were normal [4].
• In study III, hyperinsulinemia normalized glycogen formation, glycolysis, and lipid oxidation but did not normalize the elevated nonoxidative glycolysis or the decreased glucose oxidation [5].

Psychiatry related information on Glycolysis

• The marked inhibition of brain and muscles phosphofructokinase (the rate-limiting enzyme in glycolysis) induced by Li+, may play an important role in the mechanism of the therapeutic action of this agent in the manic state [6].
• The capacity for glycolysis in muscle biopsies obtained from long-term heavy alcohol drinking patients has been compared with tissue from control subjects by assay in vitro of the total activities of glycogen phosphorylase, phosphofructokinase and fructose 1,6-bisphosphatase, key regulatory enzymes in the anaerobic glycolytic pathway [7].
• Time-response studies with Ca(2+)-ionophore A23187 have revealed dual effects on the distribution of phosphofructokinase (PFK) (EC 2.7.1.11), the rate-limiting enzyme of glycolysis, between the cytoskeletal and cytosolic (soluble) fractions of the cell [8].
• It is suggested that acetylcholine liberated from sympathetic fibres causes the activation of glycolysis in muscles, which in its turn induces vasodilation in resting skeletal muscles and increase of muscle performance during emotional stress [9].

High impact information on Glycolysis

• Methylglyoxal modification of mSin3A links glycolysis to angiopoietin-2 transcription [10].
• The posttranslational modification of proteins by methylglyoxal, a highly reactive compound derived from glycolysis, may contribute to aging, diabetes, and other disorders [11].
• Methylglyoxal is a highly reactive dicarbonyl degradation product formed from triose phosphates during glycolysis [10].
• Thus, reduced nonoxidative glucose disposal (glycogen synthesis and glycolysis) accounted for virtually all the defect in overall glucose uptake (1.19 +/- 0.24 vs. 3.34 +/- 0.44 mg per minute per kilogram, P less than 0.001) [12].
• In studies in volunteers (n = 18) and in patients with severe burns who were in a hypermetabolic state (n = 18), we used stable-isotope tracers to quantify substrate cycling in the pathways of glycolysis and gluconeogenesis and a cycle involving the simultaneous breakdown and synthesis of stored triglyceride (triglyceride-fatty acid cycle) [13].

Chemical compound and disease context of Glycolysis

• The concentration requirements for glucose, mannose, and fructose by CM-injured L1210 cells correlated with the concentrations required to support maximal glycolysis of these sugars by other murine ascites cells [14].
• These findings indicated that excess purine degradation occurred in the exercising muscles of patients with glycogen storage disease types V and VII, and suggested that the ATP pool in the exercising muscles may be deranged because of defective glycogenolysis or glycolysis [15].
• In Ehrlich ascites tumor cells grown in tissue culture, 10 mM methionine inhibited glycolysis by about 50% [16].
• METHODS AND RESULTS: To determine whether promoting anaerobic glycolysis during ischemia by buffering H+ results in improved preservation of the hypertrophied heart, we studied the effect of a histidine-containing solution (HBS) on recovery of contractile function and energetic state [17].
• 2,5-Anhydromannitol also inhibits glycolysis in Ehrlich ascites cells, but the tumor cells, unlike hepatocytes, must be treated with 2,5-anhydromannitol prior to exposure to glucose to obtain the inhibition [18].

Biological context of Glycolysis

• We have cloned the gene for pig muscle phosphohexose isomerase (PHI) (EC 5.3.1.9) which catalyses the conversion of glucose-6-phosphate to fructose-6-phosphate, an obligatory step in glycolysis, and determined its amino-acid sequence [19].
• The results showed that glycolysis was more effective than oxidative phosphorylation in preventing ATP-sensitive K+ channels from opening [20].
• Because most cancer cells maintain their ATP production through aerobic glycolysis, these data may explain the molecular basis by which DNA-damaging agents can selectively induce tumor cell death independent of p53 or Bcl-2 family proteins [21].
• Inhibitors of aerobic (NaCN) and anerobic (2-deoxyglucose, NaF) glycolysis and pinocytosis, of protein biosynthesis (cycloheximide), and of cytoskeletal function (cytochalasin B and D, colchicine, podophyllotoxin, taxol) did not reduce the rate or extent of FcRII modulation [22].
• Interference of glycogenolysis with glycolysis in pancreatic islets from glucose-infused rats [23].

Anatomical context of Glycolysis

• This alteration of the redox state of the erythrocyte leads to inhibition of glycolysis at the level of glyceraldehyde 3-phosphate dehydrogenase and rapid decline in cellular energy (ATP) stores [24].
• Although T cells increase glucose uptake and glycolysis during an immune response, the signaling pathways that regulate these increases remain largely unknown [25].
• Skeletal muscle glycolysis, oxidation, and storage of an oral glucose load [26].
• In this issue of Neuron, Voutsinos-Porche et al. provide evidence that astrocyte uptake of synaptic glutamate triggers astrocytic glycolysis and release of lactate, which in turn nourishes neurons and sustains neuronal activity [27].
• Mechanism of the diastolic dysfunction induced by glycolytic inhibition. Does adenosine triphosphate derived from glycolysis play a favored role in cellular Ca2+ homeostasis in ferret myocardium [28]?

Associations of Glycolysis with chemical compounds

• Mannose effects occurred during the first 24 hours of culture and were attended by modes inhibition of the glycolysis that constitutes the principal energy pathway at this stage of development [29].
• Phosphoglycerate kinase (PGK) (ATP:3-phospho-D-glycerate 1-phosphotransferase, EC 2.7.2.3) is a metabolic enzyme functioning in the Embden-Meyerhof pathway that converts glucose (or fructose) to pyruvate [30].
• Phosphoglycerate kinase (PGK), a key enzyme in glycolysis, catalyses the transfer of a phosphoryl-group from 1,3-bisphosphoglycerate to ADP to form 3-phosphoglycerate and ATP [31].
• Inhibitors of glycolysis and of the soluble adenosine triphosphate-dependent proteolytic pathway decreased the protein degradation induced by nitrite, whereas inhibitors of lysosomal proteolysis had no effect [32].
• To investigate the mechanisms by which heat affects cancer cells, we used 5-thio-D-glucose, an inhibitor of glycolysis in HeLa S-3 cells, under aerobic and hypoxic conditions at temperatures ranging from 37 degrees to 43 degrees C. Drug alone or heat alone killed a minimum number of cells under aerobic or hypoxic conditions [33].

Gene context of Glycolysis

• Only one gene coding for glyceraldehyde 3-phosphate dehydrogenase (GAPDH, EC 1.2.1.12), a key enzyme in the control of glycolysis, is known to be functional in man, mouse, rat and chicken [34].
• Furthermore, CD28 controls a primary response pathway, inducing a level of glucose uptake and glycolysis in excess of that needed to maintain cellular ATP/ADP levels or macromolecular synthesis [25].
• Enhanced glycerol production caused by overexpression of GPD1 encoding glycerol-3-phosphate dehydrogenase also suppressed the growth defect of ggs1/tps1 delta mutants, suggesting a novel role for glycerol production in the control of glycolysis [35].
• Phosphofructokinase (PFK) plays a major role in glycolysis [36].
• 6-Phosphofructokinase (PFK) plays a central role in the regulation of glycolysis in both normal and neoplastic cells [37].

Analytical, diagnostic and therapeutic context of Glycolysis

• During these studies, we determined rates of glucose uptake, glycolysis (both with 3[3H] glucose), glycogen synthesis (determined as glucose uptake minus glycolysis), carbohydrate oxidation (by indirect calorimetry) and nonoxidative glycolysis (determined as glycolysis minus carbohydrate oxidation) [38].
• We disrupted Gapds expression by gene targeting to selectively block sperm glycolysis and assess its relative importance for in vivo sperm function [39].
• Muscle beta-enolase deficiency should be considered in the differential diagnosis of metabolic myopathies due to inherited defects of distal glycolysis [40].
• After 7 days of insulin or vehicle infusion, in vivo insulin action was determined in all rats using a 2-h hyperinsulinemic (1 mU/min) euglycemic clamp with [3-3H]glucose infusion to quantitate whole-body glucose uptake, glycolysis, glucose storage (total glucose uptake minus glycolysis), and hepatic glucose production [41].
• Rates of glycolysis and glycogen synthesis were assessed after treatment by monitoring 1,6-(13)C(2) glucose label incorporation into 1-(13)C glycogen, 3-(13)C lactate, and 3-(13)C alanine during a euglycemic ( approximately 7-8 mmol/l)-hyperinsulinemic (10 mU. kg(-1). min(-1)) clamp [42].

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