Activation of liver cytosol phosphoenolpyruvate carboxykinase by Ca2+ through intracellular redistribution of Mn2+.
Calcium has no known direct effect on phosphoenolpyruvate carboxykinase from rat liver cytosol. However, addition of calcium salts to liver postnuclear supernatant led to an increase in assayable enzyme activity in cytosols. This indicates that mitochondria and microsomes present in postnuclear supernatant can participate in observed enzyme activation. The stimulation of phosphoenolpyruvate carboxykinase was prevented by the manganese complexion 1-(2-pyridylazo)-2-naphthol, was not additive with activation by MnCl2 and was inhibited by La3+, Sr2+ and ruthenium red. These data indicate that manganese and mitochondrial or microsomal calcium carriers participate in the mechanism of indirect calcium effect. Measuring of manganese content in cytosols directly, by atomic absorption spectrometry, has provided evidence that there is a pool of manganese associated with mitochondrial and microsomal fraction of rat liver that can be mobilized to the cytosol by calcium ions. The direct addition of this pool of manganese to the cytosol caused the stimulation of phosphoenolpyruvate carboxykinase activity to the same levels as did calcium ions in the postnuclear supernatant. It is postulated that calcium can effect enzyme activity indirectly by releasing manganese from specific cellular compartments into the cytosol.
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002412:Cations; D002614:Chelating Agents; D003600:Cytosol / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology*; D008297:Male; D008345:Manganese / Q000378:metabolism* / Q000502:physiology; D009284:Naphthols; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism*; D051381:Rats; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
D002412:Cations; D002614:Chelating Agents; D009284:Naphthols; C041728:1-(2-pyridylazo)-2-naphthol; D008345:Manganese; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D002118:Calcium