Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.9 (glucose-6-phosphatase)
3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An adult woman with hypoglycemia, hyperlactatemia, hyperuricemia, hypertriglyceridemia, hyperketonemia and inability to make new glucose from galactose, fructose, glycerol and alanine was found to have no hepatic glucose-6-phosphatase and deficient fructose-1,6-diphosphatase. Nonautonomous hyperglucagonemia was demonstrated and shown to contribute to the hyperlactatemia and hyperketonemia. A paradoxic hyperlactatemic response to glucose and galactose was observed. Studies of substrate utilization showed prompt adaptation to changes in dietary supply of energy which probably accounted for her never having experienced symptoms of hypoglycemia.
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PMID:Combined deficiency of glucose-6-phosphatase and fructose-1, 6-diphosphatase. Studies of glucagon secretion and fuel utilization. 20 39

Other investigators have shown that fructose infusion in normal man and rats acutely depletes hepatic ATP and P(i) and increases the rate of uric acid formation by the degradation of preformed nucleotides. We postulated that a similar mechanism of ATP depletion might be present in patients with glucose-6-phosphatase deficiency (GSD-I) as a result of ATP consumption during glycogenolysis and resulting excess glycolysis. The postulate was tested by measurement of: (a) hepatic content of ATP, glycogen, phosphorylated sugars, and phosphorylase activities before and after increasing glycolysis by glucagon infusion and (b) plasma urate levels and urate excretion before and after therapy designed to maintain blood glucose levels above 70 mg/dl and thus prevent excess glycogenolysis and glycolysis. Glucagon infusion in seven patients with GSD-I caused a decrease in hepatic ATP from 2.25 +/- 0.09 to 0.73 +/- 0.06 mumol/g liver (P <0.01), within 5 min, persisting in one patient to 20 min (1.3 mumol/g). Three patients with GSD other than GSD-I (controls), and 10 normal rats, showed no change in ATP levels after glucagon infusion. Glucagon caused an increase in hepatic phosphorylase activity from 163 +/- 21 to 311 +/- 17 mumol/min per g protein (P <0.01), and a decrease in glycogen content from 8.96 +/- 0.51 to 6.68 +/- 0.38% weight (P <0.01). Hepatic content of phosphorylated hexoses measured in two patients, showed the following mean increases in response to glucagon; glucose-6-phosphate (from 0.25 to 0.98 mumol/g liver), fructose-6-phosphate (from 0.17 to 0.45 mumol/g liver), and fructose-1,6-diphosphate (from 0.09 to 1.28 mumol/g) within 5 min. These changes, except for glucose-6-phosphate, returned toward preinfusion levels within 20 min. Treatment consisted of continuous intragastric feedings of a high glucose dietary mixture. Such treatment increased blood glucose from a mean level of 62 (range 28-96) to 86 (range 71-143) mg/dl (P <0.02), decreased plasma glucagon from a mean of 190 (range 171-208) to 56 (range 30-70) pg/ml (P <0.01), but caused no significant change in insulin levels. Urate output measured in three patients showed an initial increase, coinciding with a decrease in plasma lactate and triglyceride levels, then decreased to normal within 3 days after treatment. Normalization of urate excretion was associated with normalization of serum uric acid. We suggest that the maintenance of blood glucose levels above 70 mg/dl is effective in reducing serum urate levels and that transient and recurrent depletion of hepatic ATP due to glycogenolysis is contributory in the genesis of hyperuricemia in untreated patients with GSD-I.
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PMID:ATP depletion, a possible role in the pathogenesis of hyperuricemia in glycogen storage disease type I. 27 29

Type I glycogen storage disease (GSD-I) is due to the deficiency of glucose-6-phosphatase activity in the liver, kidney and intestine. Although kidney enlargement occurs in GSD-I, renal disease has not been considered a major problem until recently. In older patients (more than 20 years of age) whose GSD-I disease has been ineffectively treated, virtually all have disturbed renal function, manifested by persistent proteinuria; many also have hypertension, renal stones, altered creatinine clearance or a progressive renal insufficiency. Glomerular hyperfiltration is seen in the early stage of the renal dysfunction and can occur before proteinuria. In younger GSD-I patients, the hyperfiltration is usually the only renal abnormality found; and, in some patients, microalbuminuria develops before clinical proteinuria. The predominant underlying renal pathology is focal segmental glomerulosclerosis. Renal stones and/or nephrocalcinosis are also common findings. Amyloidosis and Fanconi-like syndrome can occur, but rarely. The risk factors for developing the glomerulosclerosis in GSD-I include hyperfiltration, hypertension, hyperlipidemia and hyperuricemia. Dietary therapy with cornstarch and/or nasogastric infusion of glucose, aimed at maintaining normoglycemia, corrects metabolic abnormalities and improves the proximal renal tubular function. Long-term trial will be needed to assess whether the dietary therapy may prevent the evolution or the progression of the renal disease.
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PMID:Type I glycogen storage disease: kidney involvement, pathogenesis and its treatment. 202 44

A study of 20 cases of glycogen storage disease type I has shown differences from the classical picture. Hyperuricemia was observed in fewer than half of the cases. All patients had increased triglycerides in serum, but fewer than two thirds had increased concentrations of total cholesterol. There was a consistent increase of aminotransferases in serum. Many textbooks discuss hyperuricemia, lactic acidemia, and lipidemia in this disease without mentioning aminotransferases, and above-normal values for these enzymes ought to be given consideration, to avoid misdiagnosis. Glycogen storage disease type IB was detected by comparing glucose-6-phosphatase (EC 3.1.3.9) activity in frozen and unfrozen portions of the same liver biopsy. Latent activity, which appeared after freezing, increased the total activity to within the normal range (4.7-9.1 mumol/min per gram of tissue, wet weight) in type IB, but not in type IA.
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PMID:Glycogen storage disease type I: laboratory data and diagnosis. 282 93

Studies were performed to determine whether hypoglycemia or the glucagon response to hypoglycemia increases uric acid production in glycogen storage disease type I (glucose-6-phosphatase deficiency). Three adults with this disease had hyperuricemia (serum urate, 11.3-12.4 mg/dl) and reduced renal clearance of urate (renal urate clearance, 1.1-3.1 ml/min). These abnormalities were improved in one patient by intravenous glucose infusion for 1 mo, suggesting a role for hypoglycemia and its attendant effects on urate metabolism and excretion. A pharmacologic dose of glucagon caused a rise in serum urate from 11.4 to 13.0 mg/dl, a ninefold increase in urinary excretion of oxypurines, a 65% increase in urinary radioactivity derived from radioactively labeled adenine nucleotides, and a 90% increase in urinary uric acid excretion. These changes indicate that intravenous glucagon increases ATP breakdown to its degradation products and thereby stimulates uric acid production. To observe whether physiologic changes in serum glucagon modulate ATP degradation, uric acid production was compared during saline and somatostatin infusions. Serum urate, urinary oxypurine, radioactivity, and uric acid excretion increased during saline infusion as patients became hypoglycemic. Infusion of somatostatin suppressed these increases despite hypoglycemia and decreased the elevated plasma glucagon levels from a mean of 81.3 to 52.2 pg/ml. These data suggest that hypoglycemia can stimulate uric acid synthesis in glucose-6-phosphatase deficiency. Glucagon contributes to this response by activating ATP degradation to uric acid.
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PMID:Hyperuricemia in glycogen storage disease type I. Contributions by hypoglycemia and hyperglucagonemia to increased urate production. 285 25

Patients with deficient activity of hepatic glucose-6-phosphatase (glycogen storage disease type I [GSD-I]) have fasting-induced hypoglycemia, lactic acidemia, hyperuricemia, hyperlipidemia, and a markedly increased capacity for ethanol elimination. The mechanism(s) responsible for the rapid ethanol elimination is not known but has been thought to be directly related to the enzyme defect. We postulated however, that the increased elimination of ethanol was an adaptive phenomenon that would revert toward normal with correction of other blood abnormalities by long-term maintenance of normal blood glucose concentration. Six patients were observed before treatment (group A), and four of the six were observed again 3 to 6 months after dietary treatment had normalized all blood abnormalities (group B). Patients received 16 ml/m2 absolute ethanol as a 5% solution in 0.9% sodium chloride over a 20-minute period. The rate of ethanol elimination was significantly greater (P less than 0.03) in group A than in group B (55.1 +/- 11.1 vs. 37.5 +/- 8.6 mg/dl/hr). Changes in lactate level after ethanol were also significant between the two groups (P less than 0.005). Group A showed a decrease from 9.4 +/- 0.5 to 6.4 +/- 0.4 mEq/L, whereas group B showed an increase in lactate level from 2.7 +/- 0.2 to 4.4 +/- 0.64 mEq/L. Ethanol induced no significant change in blood glucose concentration in group A, whereas there was a significant increase (P less than 0.03) in group B from 93 +/- 6 to 123 +/- 9 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Rapid ethanol elimination in patients with type I glycogen storage disease is an adaptive change resulting from recurrent hypoglycemia. 345 5

Abnormal lipid transport is one of the more severe pathophysiological manifestations of glucose-6-phosphatase deficiency (glycogen storage disease, type I: GSD-I). To characterize further lipoprotein abnormalities in this inborn error of glycogen metabolism, we determined the levels of serum apolipoproteins (Apo) A-I, A-II, B, C-I, C-II, C-III, D, and E in 10 male and 12 female patients, 1-37 yr of age. Results showed that patients with GSD-I have a unique apolipoprotein profile characterized by normal or slightly decreased levels of ApoA-I and ApoA-II, reduced concentrations of ApoD, and significantly increased levels of ApoC-I and ApoC-II (p less than 0.01) and ApoB, ApoC-III, and ApoE (p less than 0.0001) in comparison with age- and sex-matched normolipidemic controls. However, there was some overlap of values in patients and controls for each of the lipid and apolipoprotein constituents with the exception of ApoC-III. This finding supported by the results of the logistic regression analysis showed that the concentration of ApoC-III is the best criterion for distinguishing patients with GSD-I from control subjects and the most characteristic feature of the deranged lipid transport system in this deficiency disease. It remains to be clarified, however, whether the ApoC-III concentrations in patients with GSD-I reflect the degree of other metabolic and clinical manifestations of this disease such as hyperlacticacidemia, hyperuricemia, and growth retardation.
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PMID:The serum apolipoprotein profile of patients with glucose-6-phosphatase deficiency. 385 88

There has been an explosion of knowledge in disorders of purine and pyrimidine metabolism during the last 20 years. During this time, more than 10 diseases have been discovered and their metabolic bases studied. Hyperuricemia and gout remain the most common clinical disorder. Rarely these disorders are explainable by an inherited enzyme abnormally, such as hypoxanthine-guanine phosphoribosyltransferase deficiency, phosphoribosyl-pyrophosphate synthetase deficiency, or glucose-6-phosphatase deficiency. The description of immunodeficiency syndromes in association with purine enzyme deficiency has led to a novel area of investigation encompassing the biochemical basis for immune function. Although less information is available concerning the other diseases associated with renal calculi, myopathy, anemia, and central nervous system dysfunction, further research will elucidate important metabolic relationships. These will no doubt expand our understanding of the pathogenesis of these disorders and provide innovative therapeutic approaches.
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PMID:Disorders associated with purine and pyrimidine metabolism. 609 39

Glycogen storage disease type Ib has all the clinical manifestations of glycogen storage disease type Ia such as hepatomegaly, growth retardation, bleeding tendency, hypoglycemia, hyperlactacidemia, hyperuricemia, hyperlipidemia, impaired platelet function plus neutropenia. The overall glucose-6-phosphatase activity in disrupted microsomes from liver is normal whereas glucose-6-phosphate translocase, the first enzyme in the glucose-6-phosphate transport system is absent. There is no glucose-6-phosphatase activity in vivo. Recent results show that in granulocytes the glucose-6-phosphate-dependent hexosemonophosphate-shunt is impaired.
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PMID:Glycogen storage disease type Ib. 631 72

Type IB Glycogen storage disease (GSD) is a new variant of type I Glycogen storage disease. It is characterized by same clinical findings: hepatomegaly, fasting hypoglycemia, hyperlipidemia, hyperuricemia, lactic acidosis, renal enlargement, short stature; but it distinguish for normal glucose-6-phosphatase hepatic activity in vitro. The involvement is in G-6-P transport system. Recently has been described in some patients with GSD IB, neutropenia and defective neutrophil mobility. In this report the authors described two family cases of GDS IB that one characterized by severe neutropenia.
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PMID:[Neutropenia in glycogenesis I B]. 659 20


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