scholarly journals Properties of the phosphonomethyl isosteres of two phosphate ester glycolytic intermediates

1974 ◽  
Vol 141 (3) ◽  
pp. 725-728 ◽  
Author(s):  
Donald Stribling

The enzymic synthesis of the 1-phosphonomethyl isostere of fructose 1,6-diphosphate in which the 1-phosphate (–OPO3H2) is replaced by the phosphonomethyl group (–CH2PO3H2) is described. The kinetic properties of this fructose diphosphate isostere and of 4-hydroxy-3-oxobutylphosphonic acid, an isostere of dihydroxyacetone phosphate, with aldolase (EC 4.1.2.13), fructose diphosphatase (EC 3.1.3.11) and glycerol phosphate dehydrogenase (EC 1.1.1.8) are described (see Table 1).

1990 ◽  
Vol 68 (7) ◽  
pp. 870-876
Author(s):  
J. K. Barclay ◽  
T. E. Graham ◽  
B. R. Wolfe ◽  
J. Van Duk ◽  
B. A. Wilson

Does the stimulatory effect of circulating catecholamines counteract the inhibitory effect of acidosis on skeletal muscle metabolism? To investigate this possibility, we studied gastrocnemii in dogs breathing either air (n = 10) or 4% carbon dioxide in air (n = 10) at rest and during contractions. In five dogs from each group, we infused propranolol into the arterial supply of the right and left muscles for 40 min. After 30 min of infusion, the left muscle was stimulated at 3 Hz for 10 min. During the 10th min of contractions, we removed and froze both muscles in liquid nitrogen. Oxygen uptake and blood flow to the left muscle prior to or during stimulation was not affected by acidosis either with or without propranolol. Glycogen concentration in resting muscle was unaffected by acidosis with or without propranolol. There was an acidosis related decrease of approximately 50% in the glycolytic intermediates (glucose 6-phosphate, fructose 1,6-diphosphate, α-glycerol phosphate, and dihydroxyacetone phosphate) in unstimulated muscles without β-blockade. At rest, acidosis decreased muscle lactate by 50% with and 64% without propranolol, but lactate release was decreased only with acidosis without propranolol (1.4–0.1 μmol/kg∙s). Acidosis without propranolol had no effect on the changes in glycogen concentration or the change in the concentration of glycolytic intermediates resulting from contractions. In β-blocked muscle, the difference between stimulated and unstimulated concentrations of glycogen and glycolytic intermediates including lactate was 20–50% smaller with acidosis. Thus, with β-blockade, the acidotic effects at rest disappeared and an inhibition of the metabolic adjustment to contractions appeared, indicating that circulating catecholamines do modify some metabolic effects of acidosis.Key words: oxidative muscle, glycogen, lactate efflux, glycolytic intermediates, β-blockade.


2021 ◽  
Author(s):  
Alexandre K Dube ◽  
Nicolas Malenfant ◽  
Florence Ladonne ◽  
Amanda Piano ◽  
Karamat Mohammad ◽  
...  

Loss of membrane raft integrity, metabolic dysregulation and inflammation are hallmarks of chronic diseases and aging. It is not well understood how the stress response itself may contribute to the manifestation of these common traits. To explore this question, we screened the model organism S. cerevisiae, for the secretion of glycosylphosphatidylinositol-anchored proteins (GPI-APs) as a proxy for membrane raft instability. It is shown here that the multiple cellular dysfunctions previously described for a defect in the methylation pathway for phosphatidyl choline (PC) synthesis (opi3Δ) are linked with GPI-APs secretion. They collectively result from the sustained activation of the mitogen-activated protein kinase (MAPK) Hog1p. Through modifying the dihydroxyacetone phosphate / glycerol-3-phosphate ratio, activated MAPK promotes phospholipid gene de-repression and interferes with GPI anchor synthesis. Rewiring the three carbon metabolism, namely by deleting the mitochondrial glycerol phosphate dehydrogenase, abrogated the opi3Δ mutant pleiotropic phenotypes identifying key targets to counteract MAPK-induced cellular dysfunctions.


1974 ◽  
Vol 141 (3) ◽  
pp. 715-719 ◽  
Author(s):  
Henry B. F. Dixon ◽  
Michael J. Sparkes

Analogues of dihydroxyacetone phosphate and of 3-phosphoglycerate were made in which the phosphate group, –O–PO3H2, is replaced by the phosphonomethyl group, –CH2–PO3H2. The analogue of dihydroxyacetone phosphate is a substrate for aldolase and glycerol 1-phosphate dehydrogenase (Stribling, 1974), but not for triose phosphate isomerase. The analogue of 3-phosphoglycerate oxidizes NADH under the combined action of 3-phosphoglycerate kinase and glyceraldehyde 3-phosphate dehydrogenase if ATP is added. Thus four out of the five glycolytic enzymes tested handle the phosphonomethyl compounds like the natural phosphates.


1995 ◽  
Vol 60 (13) ◽  
pp. 4294-4295 ◽  
Author(s):  
Ramon Alajarin ◽  
Eduardo Garcia-Junceda ◽  
Chi-Huey Wong

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