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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1994-10-27
pubmed:abstractText
Previously, we have shown in experiments with isolated mitochondria that almitrine, a drug used for patients with chronic lung disease, affects the H+/ATP stoichiometry of the F0F1-ATPase [Rigoulet, M., Fraisse, L., Ouhabi, R., Guérin, B., Fontaine, E. & Leverve, X. M. (1990) Biochim. Biophys. Acta 1018, 91-97]. In the present study, we have investigated the effect of almitrine on gluconeogenesis and oxygen consumption in isolated hepatocytes. Almitrine decreased both the cytosolic and mitochondrial ATP/ADP ratios but had no effect on oxygen consumption in cells incubated with and without octanoate. This must have been due to a double effect. On the one hand, a decrease in the ATP/ADP ratio decreases ATP utilization; on the other hand, in the presence of almitrine more oxygen is required to synthesize ATP. Almitrine did affect gluconeogenesis from various substrates (lactate + pyruvate, glycerone or fructose), but had no effect on glycerol or glutamine metabolism. The effect on gluconeogenesis from glycerone was due to an increase in glycolytic flux. The rate of lactate + pyruvate production increased whereas there was no effect on glycerone utilization. This effect was caused by an activation of pyruvate kinase. Our data indicate that this enzyme is an extremely sensitive sensor of the cytosolic ATP/ADP ratio. Hence, under our experimental conditions, the cytosolic ATP/ADP ratio decrease affects only the balance between glucose and lactate + pyruvate productions, and not the phosphorylation of glycerone, the first and controlling step of this pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0014-2956
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
224
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
967-74
pubmed:dateRevised
2007-7-23
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Decrease in cytosolic ATP/ADP ratio and activation of pyruvate kinase after in vitro addition of almitrine in hepatocytes isolated from fasted rats.
pubmed:affiliation
Laboratoire de Thérapeutique, Université Joseph Fourier, Grenoble, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't