Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.1 (hexokinase)
 5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The storage lesion which limits the shelf life of human blood in blood banking is associated with a metabolic loss of 2,3-diphosphoglycerate and ATP. This metabolic loss is driven by intracellular ATPase which are usually considered to include the ion pumps and the reactions which maintain the discoid shape of the human erythrocyte. Under the acidic conditions of blood storage, the energy-yielding reactions of the glycolytic pathway are restricted at the hexokinase and phosphofructokinase steps. We show here that under such circumstances the enzyme of the diphosphoglycerate shunt, diphosphoglycerate mutase/phosphatase and the glycolytic enzyme phosphoglycerate kinase can form a futile cycle with ATPase activity. This ATPase activity responds to 2-phosphoglycolate which is known to activate both diphosphoglycerate mutase and diphosphoglycerate phosphatase reactions. When the enzymes of the futile cycle are combined with the enzymes of the lower glycolytic pathway in a reconstitution experiment designed to represent conditions within the stored erythrocyte, the futile cycle does provide an ATPase activity which results in the metabolic loss of 2,3-diphosphoglycerate. An isotope incorporation experiment demonstrates that the futile cycle is active in glucose-depleted erythrocytes.
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PMID:A futile cycle in erythrocyte glycolysis. 406 53

This study was undertaken to assess the effect of propane-1,2-diol(PD) ingestion on carbohydrate metabolism in female rat erythrocytes. For this purpose, two different groups of adult albino female rats were treated orally with PD at two different dose levels of 73 and 294 mg 100 g-1 body wt. The blood samples drawn from the retro-orbital sinus prior to the treatment served as the controls, whereas the treated samples were collected at peak periods (1/2 and 2 h) 2 and 7 days after the treatment. A single dose of PD was found to elevate levels of blood glucose, lactate, pyruvate and the lactate/pyruvate ratio at the peak periods (P < 0.001) and after 2 days (P < 0.001) in both the groups. A significant (P < 0.05) increase in the contents of erythrocyte 2,3-diphosphoglycerate (2,3-DPG) was observed only at the peak periods. All these parameters returned to their base level after 7 days of treatment. The activities of hexokinase (HK), 2,3-diphosphoglycerate phosphatase (2,3-DPG Pase), lactate dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G-6-PD), 6-phosphogluconate dehydrogenase (6-PGD) and aldehyde reductase II (AR II) declined markedly, whereas those of pyruvate kinase (PK) and aldose reductase increased as a result of PD ingestion. The changes in the activities of 2,3-DPG Pase and LDH were persistent up to 8 days post-treatment. The [14C]glucose flux through glycolysis and the hexose monophosphate shunt pathway in erythrocytes was found to be lowered (P < 0.001) in response to PD treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of propane-1,2-diol ingestion on carbohydrate metabolism in female rat erythrocytes. 844 Aug 77

Alzheimer disease (AD) is the most common dementing illness. Metabolic defects in the brain with aging contribute to the pathogenesis of AD. These changes can be found systematically and thus can be used as potential biomarkers. Erythrocytes (RBCs) are passive "reporter cells" that are not well studied in AD. In the present study, we analyzed an array of glycolytic and related enzymes and intermediates in RBCs from patients with AD and non-Alzheimer dementia (NA), age-matched controls (AC) and young adult controls (YC). AD is characterized by higher activities of hexokinase, phosphofructokinase, and bisphosphoglycerate mutase and bisphosphoglycerate phosphatase in RBCs. In our study, we observed that glycolytic and related enzymes displayed significantly lower activities in AC. However, similar or significantly higher activities were observed in AD and NA groups as compared to YC group. 2,3-diphosphoglycerate (2,3-DPG) levels were significantly decreased in AD and NA patients. The pattern of changes between groups in the above indices strongly correlates with each other. Collectively, our data suggested that AD and NA patients are associated with chronic disturbance of 2,3-DPG metabolism in RBCs. These defects may play a pivotal role in physiological processes, which predispose elderly subjects to AD and NA.
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PMID:Age-related defects in erythrocyte 2,3-diphosphoglycerate metabolism in dementia. 2412 30

Alzheimer disease (AD) is one of the most common neurodegenerative disorders widely occurring among the elderly. The pathogenic mechanisms involved in the development of this disease are still unknown. In AD, in addition to brain, a number of peripheral tissues and cells are affected, including erythrocytes. In this study, we analyzed glycolytic energy metabolism, antioxidant status, glutathione, adenylate and proteolytic systems in erythrocytes from patients with AD and compared with those from age-matched controls and young adult controls. Glycolytic enzymes hexokinase, phosphofructokinase, bisphosphoglycerate mutase and bisphosphoglycerate phosphatase displayed lower activities in agematched controls, and higher activities in AD patients, as compared to those in young adult control subjects. In both aging and AD, oxidative stress is increased in erythrocytes whereas elevated concentrations of hydrogen peroxide and organic hydroperoxides as well as decreased glutathione/glutathione disulfide ratio and glutathione transferase activity can be detected. These oxidative disturbances are also accompanied by reductions in ATP levels, adenine nucleotide pool size and adenylate energy charge. Caspase-3 and calpain activities in age-matched controls and AD patients were about three times those of young adult controls. 2,3-diphosphoglycerate levels were significantly decreased in AD patients. Taken together these data suggest that AD patients are associated with chronic disturbance of 2,3-diphosphoglycerate metabolism in erythrocytes. These defects may play a central role in pathophysiological processes predisposing elderly subjects to dementia.
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PMID:Relationship between chronic disturbance of 2,3-diphosphoglycerate metabolism in erythrocytes and Alzheimer disease. 2629 25