Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.4.1.1 (pyruvate carboxylase)
 1,516 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 42-year-old woman developed a flu-like illness and died 8 days later with Reye's syndrome (RS). There are 26 other cases of adult-onset RS reported. Biochemical, immunologic, and molecular studies of liver, brain, and skeletal muscle revealed a non-uniform decrease in several mitochondrial residual enzyme activities in liver and brain. Pyruvate carboxylase activity was negligible. Cross-reacting material was present in normal abundance in isolated liver mitochondria for several enzymes that had reduced catalytic activity including pyruvate carboxylase. Subunit II (encoded by mitochondrial DNA) and subunit IV (encoded by nuclear DNA) of cytochrome c oxidase also were present in normal abundance with normal electrophoretic mobility. These observations, combined with pertinent findings of other investigators, allow us to speculate that the intramitochondrial matrix chemical environment is disturbed by preceding pathophysiologic events resulting in a lowered ATP/ADP ratio. The lowered intramitochondrial energetic state interferes with the refolding and assembly of imported mitochondrial proteins, causing a loss of the catalytic efficiency of these enzymes. This explains the selective vulnerability of mitochondria in RS and the non-uniform, disproportionate loss of enzyme activity.
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PMID:Adult Reye's syndrome: a review with new evidence for a generalized defect in intramitochondrial enzyme processing. 194 14

A 42-year-old man was admitted because of episodic attack of general malaise. He was lethargic and had a severe lactic acidosis and hypoglycemia. Blood chemistry and endocrinological data were normal. Glucose administration led to an improvement in the hypoglycemia but not the lactic acidosis. At autopsy, there was a massive infiltration of leukemic cells in both kidneys and in liver. Phosphoenolpyruvate carboxykinase, pyruvate carboxylase and glucose-6-phosphatase activities in patient's liver were much the same as in the control liver, but fructose-1, 6-diphosphatase activity was slightly reduced. Since circulatory failure was absent, type B lactic acidosis has to be considered. Since hypoglycemia was associated with acidosis, the severe lactic acidosis in our patient may have been due to an overproduction of lactic acid as well as to an impaired hepatic gluconeogenesis in the presence of leukemic cells.
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PMID:Lactic acidosis and hypoglycemia associated with acute leukemia. 386 4