Role of bivalent cations in the control of enzymes involved in gluconeogenesis

The role of mitochondria in modifying calcium-sensitive cytoplasmic metabolic activities. Modification of pyruvate kinase activity

“…Previous work has shown that the high sensitivity of this enzyme to Ca21 (Kachmar & Boyer, 1953;Bygrave, 1966b;Mildvan & Cohn, 1966) is mainly responsible for the inhibition of glycolysis by this ion in cell-free extracts (Geiger, 1940;Bygrave, 1966a). There is some evidence that concentrations of cytoplasmic Ca2+ may play a role in gluconeogenesis (Gevers & Krebs, 1966;Kimmich & Rasmussen, 1969;Wimhurst & Manchester, 1970), possibly through interactions at the pyruvate kinase step (Rasmussen & Nagata, 1970). Ionic control of pyruvate kinase is thus potentially important for the control of both glycolysis and gluconeogenesis.…”

Role of metal cofactors in enzyme regulation. Differences in the regulatory properties of the Neurospora crassa nicotinamide adenine dinucleotide specific isocitrate dehydrogenase depending on whether Mg2+or Mn2+ serves as divalent cation

“…It is obvious from the results presented in this study that the regulatory properties of isocitrate dehydrogenase are significantly altered by the choice of metal cofactor. Several enzymes have been shown to have different regulatory properties in the presence of Mg2+ and Mn2+, including ADP-glucose pyrophosphorylase (Centner and Preiss, 1968), several gluconogenic enzymes (Wimhurst and Manchester, 1970), and pyruvate kinase (Gabrielli and Baldi, 1973). The conclusion can be drawn from such studies that the role of metal ions in enzyme reactions is not simply as a necessary cofactor but rather as a distinct regulatory entity.…”

Effects of manganese on the activity of glycolytic and gluconeogenic enzymes in the perfused rat liver

“…Administration of manganese results in a rapid increase in serum glucose [3] and is reported to enhance glucose production by the perfused liver [4]. It is a potent activator of several glycolytic and gluconeogenic enzymes including specifically pyruvate carboxylase and phosphoenolpyruvate carboxykinase [5,6]. We here report that addition of manganese to the perfused rat liver prevents the increase in activity of the two enzymes otherwise induced by lactate.…”

“…Gluconeogenic, glycolytic and other enzymes were assayed as described previously [6,71. Perfusate glucose, lactate, pyruvate, urea and amino acids, liver K+, DNA, RNA, glycogen, amino acids and water content were also measured [ 11.…”