Hepatic phosphorylase deficiency: Its differentiation from other hepatic glycogenoses

Fernandes, J.; Koster, J.F.; Grose, W. F. A.; Sorgedrager, N.

doi:10.1136/adc.49.3.186

Cited by 45 publications

(13 citation statements)

References 14 publications

(11 reference statements)

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“…Inhibition and/or inactivation of phosphorylase a by pharmacological means is then expected to promote net glycogen synthesis from G6P provided by gluconeogenesis. Hepatic phosphorylase deficiency (22) and phosphorylase-kinase deficiency (23,24) are characterized by mild postabsorptive hypoglycemia. The efficacy of hepatic phosphorylase inhibitors to lower blood glucose in obesityrelated type 2 diabetes has been demonstrated (2).…”

mentioning

confidence: 99%

Molecular mode of inhibition of glycogenolysis in rat liver by the dihydropyridine derivative, BAY R3401: inhibition and inactivation of glycogen phosphorylase by an activated metabolite.

et al. 2000

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The racemic prodrug BAY R3401 suppresses hepatic glycogenolysis. BAY W1807, the active metabolite of BAY R3401, inhibits muscle glycogen phosphorylase a and b. We investigated whether BAY R3401 reduces hepatic glycogenolysis by allosteric inhibition or by phosphatasecatalyzed inactivation of phosphorylase. In gel-filtered liver extracts, racemic BAY U6751 (containing active BAY W1807) was tested for inhibition of phosphorylase in the glycogenolytic (in which only phosphorylase a is active) and glycogen-synthetic (for the evaluation of a:b ratios) directions. Phosphorylase inactivation by endogenous phosphatase was also studied. In liver extracts, BAY U6751 (0.9-36 µmol/l) inhibited glycogen synthesis by phosphorylase b (notwithstanding the inclusion of AMP), but not by phosphorylase a. Inhibition of phosphorylase-a-catalyzed glycogenolysis was partially relieved by AMP (500 µmol/l). BAY U6751 facilitated phosphorylase-a dephosphorylation. Isolated hepatocytes and perfused livers were tested for BAY R3401-induced changes in phosphorylase-a:b ratios and glycogenolytic output. Though ineffective in extracts, BAY R3401 (0.25 µmol/l-0.5 mmol/l) promoted phosphorylase-a dephosphorylation in hepatocytes. In perfused livers exposed to dibutyryl cAMP (100 µmol/l) for maximal activation of phosphorylase, BAY R3401 (125 µmol/l) inactivated phosphorylase by 63% but glucose output dropped by 83%. Inhibition of glycogenolysis suppressed glucose-6-phosphate (G6P) levels. Activation of glycogen synthase after phosphorylase inactivation depended on the maintenance of G6P levels by supplementing glucose (50 mmol/l). We conclude that the metabolites of BAY R3401 suppress hepatic glycogenolysis by allosteric inhibition and by the dephosphorylation of phosphorylase a.

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confidence: 99%

Molecular mode of inhibition of glycogenolysis in rat liver by the dihydropyridine derivative, BAY R3401: inhibition and inactivation of glycogen phosphorylase by an activated metabolite.

et al. 2000

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“…The diagnosis of the sex-linked form of liver phosphorylase kinase deficiency in these two patients was made by a screening procedure for hepatic glycogenosis [1] and careful assessment of phosphorylase kinase activities and glycogen contents in leucocytes and erythrocytes.…”

Section: Methodsmentioning

confidence: 99%

Lymphocyte phosphorylase kinase activities in the sex-linked form of liver phosphorylase kinase deficiency

et al. 1985

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Lymphocyte phosphorylase kinase activities were measured in normal controls and in patients with the sex-linked form of liver phosphorylase kinase deficiency. The reaction due to phosphorylase kinase activity in normal lymphocytes (2.7 X 10(6) in the reaction tube) was found to be linear within 20-60 min at 30 degrees C. The reaction was directly proportional to the concentration of lymphocytes within 1.5 X 10(6)-9.0 X 10(6), at 30 degrees C for 60 min. The phosphorylase kinase activity in normal lymphocytes, which were pre-incubated at 50 degrees C or 95 degrees C for 1 min, decreased to 60% at 50 degrees C and 10% at 95 degrees C of that after pre-incubation at 0 degree C for 1 min. The activity of normal controls was 125 +/- 23.5 U/10(10) lymphocytes. Those of the patients with liver phosphorylase kinase deficiency due to the sex-linked form were 43.5 U in case 1, 54.5 U in case 2, and 51.3 U in case 3, respectively and those of the mothers were within the normal range. These results suggest that phosphorylase kinase in lymphocytes might be form intermediate between liver and muscle phosphorylase kinase.

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“…Glucose-6-phosphatase deficiency was documented by the typical clinical/biochemical features including challenge tests according to Fernandes et al [7] and/or determination of enzyme activity.…”

Section: Methodsmentioning

confidence: 99%

Glycogen storage disease Type I. Results of treatment with frequent daytime feeding, combined with nocturnal intragastric feeding and with administration of an ?-glucosidase inhibitor

Gröbe

Ullrich

1983

Eur J Pediatr

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Seven patients with glycogen disease type I have been treated with nocturnal intragastric feeding combined with frequent daytime feeding. Follow-up shows a striking improvement in their clinical condition including growth rate. Determination of biochemical parameters reveals a significant increase in mean blood glucose levels and a significant decrease of lactate, pyruvate, alanine, uric acid, triglycerides, and SGOT in blood. Additional administration of an alpha-glucosidase inhibitor in four patients caused a significant increase in blood lactate despite unchanged blood glucose levels.

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Hepatic phosphorylase deficiency: Its differentiation from other hepatic glycogenoses

Abstract: A screening method is described to diagnose tentatively a phosphorylase deficiency on the basis of hexose and glucagon tolerance tests.

Cited by 45 publications

References 14 publications

Molecular mode of inhibition of glycogenolysis in rat liver by the dihydropyridine derivative, BAY R3401: inhibition and inactivation of glycogen phosphorylase by an activated metabolite.

Molecular mode of inhibition of glycogenolysis in rat liver by the dihydropyridine derivative, BAY R3401: inhibition and inactivation of glycogen phosphorylase by an activated metabolite.

Lymphocyte phosphorylase kinase activities in the sex-linked form of liver phosphorylase kinase deficiency

Glycogen storage disease Type I. Results of treatment with frequent daytime feeding, combined with nocturnal intragastric feeding and with administration of an ?-glucosidase inhibitor

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