Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanisms by which glycogen metabolism, glycolysis and gluconeogenesis are controlled in the liver both by hormones and by the concentration of glucose are reviewed. The control of glycogen metabolism occurs by phosphorylation and dephosphorylation of both glycogen phosphorylase and glycogen synthase catalysed by various protein kinases and protein phosphatases. The hormonal effect is to stimulate glycogenolysis by the intermediary of cyclic AMP, which activates directly or indirectly the protein kinases. The glucose effect is to activate the protein phosphatase system; this occurs by the direct binding of glucose to glycogen phosphorylase which is then a better substrate for phosphorylase phosphatase and is inactivated. Since phosphorylase a is a strong inhibitor of synthase phosphatase, its disappearance allows the activation of glycogen synthase and the initiation of glycogen synthesis. When glycogen synthesis is intense, the concentrations of UDPG and of glucose 6-phosphate in the liver decrease, allowing a net glucose uptake by the liver. Glucose uptake is indeed the difference between the activities of glucokinase and glucose 6-phosphatase. Since the Km of the latter enzyme is far above the physiological concentration of its substrate, the decrease in glucose 6-phosphate concentration proportionally reduces its activity. The control of glycolysis and of gluconeogenesis occurs mostly at the level of the interconversion of fructose 6-phosphate and fructose 1,6-bisphosphate under the action of phosphofructokinase 1 and fructose 1,6-bisphosphatase. Fructose 2,6-bisphosphate is a potent stimulator of the first of these two enzymes and an inhibitor of the second. It is formed from fructose 6-phosphate and ATP by phosphofructokinase 2 and hydrolysed by a fructose 2,6-bisphosphatase. These two enzymes are part of a single bifunctional protein which is a substrate for cyclic AMP-dependent protein kinase. Its phosphorylation causes the inactivation of phosphofructokinase 2 and the activation of fructose 2,6-bisphosphatase, resulting in the disappearance of fructose 2,6-bisphosphate. The other major effector of these two enzymes is fructose 6-phosphate, which is the substrate of phosphofructokinase 2 and a potent inhibitor of fructose 2,6-bisphosphatase; these properties allow the formation of fructose 2,6-bisphosphate when the level of glycaemia and secondarily that of fructose 6-phosphate is high.
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PMID:Mechanisms of blood glucose homeostasis. 212 8

Antibody prepared against the catalytic subunit of protein phosphatase-2A from rabbit skeletal muscle, could completely inhibit this enzyme, but did not significantly affect the activities of protein phosphatases-1, 2B and 2C. The antibody was used to establish the following points. The three forms of protein phosphatase-2A that can be resolved by ion-exchange chromatography, termed 2A0, 2A1, and 2A2, share the same catalytic subunit. The antigenic sites on the catalytic subunit of protein phosphatase-2A remain accessible to the antibody, when the catalytic subunit is complexed with the other subunits of protein phosphatases-2A0, 2A1 and 2A2. The catalytic subunits of protein phosphatase-2A from rabbit skeletal muscle and rabbit liver are very similar, as judged by immunotitration experiments. Protein phosphatase-1 and protein phosphatase-2A account for virtually all the phosphorylase phosphatase activity in dilute tissue extracts prepared from skeletal muscle, liver, heart, brain and kidney, and for essentially all the glycogen synthase phosphatase activity in dilute skeletal muscle and liver extracts. Protein phosphatase-2A is almost absent from the protein-glycogen complex prepared from skeletal muscle or liver extracts. Protein phosphatase-2A accounts for a major proportion of the phosphatase activity in dilute liver extracts towards 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, 6-phosphofructo-1-kinase, fructose 1,6-bisphosphatase, pyruvate kinase and phenylalanine hydroxylase, the major phosphorylated enzymes involved in the hormonal control of hepatic glycolysis and gluconeogenesis.
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PMID:The protein phosphatases involved in cellular regulation. Antibody to protein phosphatase-2A as a probe of phosphatase structure and function. 609 82

A protein kinase active on fructose-bisphosphatase (D-fructose-1,6-bisphosphate 1-phosphohydrolase, EC 3.1.3.11) was demonstrated in rat liver cell sap. The protein kinase activity was stimulated by cyclic AMP and coincided with the activity of cyclic AMP-dependent protein kinase type I. In addition, three different peaks of phosphoprotein phosphatase active on [32P] phosphofructose-bisphosphatase were found on chromatography of rat liver cell sap on a DEAE-cellulose column. These phosphatases needed divalent cations for full activity. 5'-AMP, a negative modulator of fructose-bisphosphatase, had no effect on the phosphorylation-de-phosphorylation reactions of the enzyme. ATP and Ca2+ did not influence the dephosphorylation reaction of fructose-bisphosphatase.
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PMID:The demonstration in rat liver cell sap of protein kinase and phosphoprotein phosphatase active on fructose-bisphosphatase. 628 6

A phosphoprotein phosphatase has been purified from rat liver cytosol. The purification involved chromatography on DEAE-cellulose. Sephacryl S-200, fast protein liquid chromatography (FPLC) and sucrose density gradient centrifugation. It resulted in an almost homogeneous enzyme with a relative molecular mass, Mr, of 90 000 by gel filtration and sucrose gradient centrifugation and Mr = 44 500 by sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE). Therefore it seems to be a dimeric enzyme. This protein phosphatase (termed PFK-phosphatase) is completely dependent on Mg2+, which can be replaced partly by Mn2+. It can be eluted from DEAE-cellulose with 120 mM NaCl, is not affected by Ca2+, 100 microM trifluoperazine or the heat-stable inhibitor-2. Inhibition occurs with phosphate, ammonium sulfate and fluoride. PFK-phosphatase dephosphorylates preferentially the alpha subunit of phosphorylase kinase (alpha/beta dephosphorylation ratio 5-10). Phosphorylase a, mixed histone and casein do not serve as substrates. The enzyme dephosphorylates effectively the key enzymes of glucose metabolism 6-phosphofructo-1-kinase, fructose 1,6-bisphosphatase, pyruvate kinase and 6-phosphofructo-2-kinase. Using this protein phosphatase and the catalytic subunit of cAMP-dependent protein kinase, a complete phosphorylation, dephosphorylation and rephosphorylation cycle was possible with 6-phosphofructo-1-kinase as substrate.
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PMID:Purification and characterization of a protein phosphatase from rat liver acting on key enzymes of glucose metabolism. 632 87