Opposite effects of dibutyryl cyclic GMP and bibutyryl cyclic AMP on glucose 1,6-diphosphate levels and the activities of glucose 1,6-diphosphate phosphatase and phosphofructokinase in diaphragm muscle (original) (raw)
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Molecular and Cellular Endocrinology, 1978
Based on previous studies which have revealed that glucose 1,6bisphosphate (Glc-1,6-P,) is a potent inhibitor of muscle hexokinase and an activator (deinhibitor) of phosphofructokinase and phosphoglucomutase, the effect of epinephrine on the levels of this regulator in rat diaphragm muscle was investigated. It was found that epinephrine caused an increase in diaphragm Glc-1,6-P, levels, accompanied by a reduction in the activity of hexokinase and an activation (deinhibition) of phosphofructokinase and phosphoglucomutase. N6-2'Qdibutyryl cyclic AMP was able to mimic all these effects of epinephrine. The concentration of glucosed-phosphate was not changed by epinephrine, under conditions in which the hormone produced an increase in cyclic AMP and Glc-1,6-P* levels and the concomitant decrease in hexokinase activity. It was also shown that Glc-1,6-Pz, in the concentration range found after epinephrine, inhibited the diaphragm hexokinase and deinhibited phosphoglucomutase. These results may suggest a mechanism of epinephrine action by which the activities of hexokinase, phosphoglucomutase and phosphofructokinase, through the action of Glc-1,6-Pz, are synchronized with the cyclic AMP-mediated activation of glycogen phosphorylase, to achieve an increase in total glycogenolysis and glycolysis and a concomitant reduction in glucose utilization by the muscle.
Biochemical Medicine and Metabolic Biology, 1987
Experiments in our laboratories as well as in those of others have revealed that glucose 1,6-bisphosphate (Glc-1,6-P*) is a powerful regulator of carbohydrate metabolism (for reviews, see Refs. l-3). The unique feature of Glc-1,6-P, is that it acts as an intracellular signal which controls the activities of several key enzymes in carbohydrate metabolism. Its intracellular concentration is controlled by different physiological and pathological conditions, leading to concomitant changes in the activities of the key enzymes which are modulated by this regulator. The intracellular levels of Glc-1,6-P* are controlled by cyclic nucleotides (4-6) and by Ca*+ (6,7). Glc-l,6-P2 was found to be involved in the mechanism of action of several hormones and pharmacologic agents (4,6,8-13). Its concentration also changes during starvation (14), anoxia, or ischemia (15,16), during differentiation (6) and growth (17-19), and in senescence (20). The intracellular levels of Glc-1,6-P, in muscle are markedly decreased in muscular dystrophy (14,21,22), as well as by treatment of normal muscle with phospholipase A2 (23), local anesthetics (lo), Ca*+ ionophore A23187 (7) and lithium (ll), leading to a marked reduction in glycolysis. All these compounds are known to induce muscle damage or weakness similar to that occurring in muscular dystrophy (24-29). ATP is a drug used in the therapy of myopathies ("Adenotriphos," Rona, UK). The mechanism of action of ATP is not known.
Specificity of glucose 1,6-bisphosphate synthesis in rabbit skeletal muscle
Comparative biochemistry and physiology. B, Comparative biochemistry, 1991
1. To compare glucose 1,6-bisphosphate synthesis in different types of cells, we partially purified (2000-fold) a glycerate 1,3 P2-dependent glucose 1,6-bisphosphate synthase from rabbit skeletal muscle. 2. In agreement with the results reported by others for mouse brain and pig skeletal muscle, the enzyme can be separated from bulk phosphoglucomutase (PGM) activity by DEAE-cellulose chromatography of crude cellular extract. This cannot be achieved on human hemolysates where glycerate 1,3-P2-dependent glucose 1,2-bisphosphate synthesis is displayed only by multifunctional PGM2 isoenzymes. 3. The Km values for glycerate 1,3-P2 (0.50 microM), glucose 1-phosphate (90 microM), Mg2+ (0.22 mM), and also pH optimum (7.8) and mol. wt (70,000) of the rabbit skeletal muscle enzyme are similar to those of the enzymes from mouse brain and human red blood cells, but they differ from those reported for the pig skeletal muscle enzyme.
International Journal of Biochemistry, 1983
Injection of serotonin (S-hydroxytryptamine) induced a marked decrease in the level of glucose 1,6-diphosphate (Glc-1,6-P,) in the rat tibialis anterior muscle. 2. Concomitant to the decrease in Glc-1,6-P,, the potent activator of phosphofructokinase and phosphoglucomutase, the activities of both these enzymes were markedly reduced by serotonin. 3. The level of Glc-1,6-P, and the activities of phosphofructokinase and phosphoglucomutase increased with age in the tibialis anterior muscle and the effect of serotonin was more pronounced in the older animals. 4. Serotonin also induced a significant increase in the level of cyclic GMP in muscle. 5. The serotonin-induced changes in the normal muscle mimic the changes in carbohydrate metabolism we found previously in muscular dystrophy.
Changes in glucose 1,6-bisphosphate content in rat skeletal muscle during contraction
Biochemical Journal, 1986
Glucose 1,6-bisphosphate, fructose 2,6-bisphosphate, glycogen, lactate and other glycolytic metabolites were measured in rat gastrocnemius muscle, which was electrically stimulated in situ via the sciatic nerve. Both the frequency and the duration of stimulation were varied to obtain different rates of glycolysis. There was no apparent relationship between fructose 2,6-bisphosphate content and lactate accumulation in contracting muscle. In contrast, glucose 1,6-bisphosphate content increased with lactate concentration during contraction. It is suggested that the increase in glucose 1,6-bisphosphate could play a role in phosphofructokinase stimulation and in the activation of the glycolytic flux during muscle contraction.