In skeletal muscle, calcium not only triggers muscle contraction but also exerts pleiotropic effects on carbohydrate metabolism. Calcium activates glycogen phosphorylase-accelerating glycogenolysis, induces GLUT 4 and activates pyruvate dehydrogenase, thus accelerating glycolysis. Calcium also inhibits glyconeogenesis. It has been reported that up to 50% of lactate generated in muscle tissue is converted in situ to glycogen. This process was called glyconeogenesis to distinguish it from gluconeogenesis, which takes place in liver and results in glucose release. Regulatory enzyme of gluconeogenesis and glyconeogenesis is fructose-1,6-bisphosphatase (FBPase) catalyzing hydrolysis of fructose-1,6-bisphosphate to fructose-6-phosphate and P_i. Liver and muscle isozyme have been found in vertebrate tissues. Kinetic properties of both isozymes are virtually the same, both require divalent metal ions like magnesium to their activity and both are activated by monovalent cations and inhibited by fructose-2,6-bisphosphate. Recently we have found that calcium is the strong inhibitor of the muscle FBPase which binds the calcium ions in a cooperative manner. The determined I_0.5 of the muscle isozyme toward calcium was 0.6 μM. On the contrary, the liver isozyme is practically insensitive to this ions. Investigating the muscle FBPase we found that the enzyme interacts with the muscle aldolase and α-actinin. We found that, in vivo FBPase colocalizes with aldolase and α-actinin on the Z-line in myocytes making a glyconeogenic metabolon. Increase of calcium concentration results in dissociation of FBPase from the Z-line, disintegration of FBPase-aldolase complex and in effect inhibition of the enzyme. At rest decrease of calcium concentration enables association of FBPase with aldolase and colocalization of both enzymes with α-actinin on the Z-line so, glyconeogenesis can proceed. Searching for the origin of the high sensitivity of the muscle FBPase toward calcium we found that in the liver isozyme, Gln 69 is present which is substituted with Glu 69 in the muscle isozyme. Hypothetically the single point mutation Gln→Glu resulted in dramatic change of the former isozyme kinetic property making the new isozyme highly sensitive to calcium ions thus enabling the regulation of glyconeogenesis by calcium signal.

• Legal notice:
  

  Copyright (c) Pielaszek Research, all rights reserved.
  The above materials, including auxiliary resources, are subject to Publisher's copyright and the Author(s) intellectual rights. Without limiting Author(s) rights under respective Copyright Transfer Agreement, no part of the above documents may be reproduced without the express written permission of Pielaszek Research, the Publisher. Express permission from the Author(s) is required to use the above materials for academic purposes, such as lectures or scientific presentations.
  In every case, proper references including Author(s) name(s) and URL of this webpage: https://science24.com/paper/10926 must be provided.