ABSTRACT
The activity of fructose-1,6-bisphosphatase (FBPase; EC 3.1.3.11) isozymes is influenced by AMP, Ca2+ and by reversible interactions with subcellular structures. In contrast to mammalian and avian isozymes, the kinetic properties of FBPases from ectothermal vertebrates are not fully described. To get some insight into mechanism of glycogen resynthesis in ectothermal vertebrates we examined the features of FBPases isolated from Cyprinus carpio skeletal muscle and liver. To investigate the evolutionary origin of the sensitivity of FBPase to effectors, we performed a phylogenetic analysis of known animal amino acids sequences of the enzyme. Based on our findings, we hypothesize that the high, mammalian-like, sensitivity of FBPase to Ca2+ is not essential for controlling the stability of glyconeogenic complex in striated muscles, instead it ensures the precise regulation of mitochondrial metabolism during prolonged Ca2+ elevation in contracting muscle fibers. Comparison of the kinetic properties of vertebrate and insect FBPases suggests that the high sensitivity of muscle isozyme to inhibitors has arisen as an adaptation enabling coordination of energy metabolism in warm-blooded animals.
Subject(s)
Adenosine Monophosphate/physiology , Calcium/physiology , Carps/metabolism , Fructose-Bisphosphatase/metabolism , Liver/enzymology , Muscles/enzymology , Adenosine Monophosphate/pharmacology , Animals , Calcium/pharmacology , Evolution, Molecular , Kinetics , Liver/metabolism , Muscles/metabolism , PhylogenyABSTRACT
Recently a gluconeogenic enzyme was discovered-fructose 1,6-bisphosphatase (FBPase)-that localizes in the nucleus of a proliferating cell, but its physiological role in this compartment remains unclear. Here, we demonstrate the link between nuclear localization of FBPase and the cell cycle progression. Results of our studies indicate that in human and mouse squamous cell lung cancer, as well as in the HL-1 cardiomyocytes, FBPase nuclear localization correlates with nuclear localization of S and G2 phase cyclins. Additionally, activity and expression of the enzyme depends on cell cycle stages. Identification of FBPase interacting partners with mass spectrometry reveals a set of nuclear proteins involved in cell cycle regulation, mRNA processing and in stabilization of genomic DNA structure. To our knowledge, this is the first experimental evidence that muscle FBPase is involved in cell cycle events.