Control of glycogen deposition.
Traditionally, glycogen synthase (GS) has been considered to catalyze the key step of glycogen synthesis and to exercise most of the control over this metabolic pathway. However, recent advances have shown that other factors must be considered. Moreover, the control of glycogen deposition does not follow identical mechanisms in muscle and liver. Glucose must be phosphorylated to promote activation of GS. Glucose-6-phosphate (Glc-6-P) binds to GS, causing the allosteric activation of the enzyme probably through a conformational rearrangement that simultaneously converts it into a better substrate for protein phosphatases, which can then lead to the covalent activation of GS. The potency of Glc-6-P for activation of liver GS is determined by its source, since Glc-6-P arising from the catalytic action of glucokinase (GK) is much more effective in mediating the activation of the enzyme than the same metabolite produced by hexokinase I (HK I). As a result, hepatic glycogen deposition from glucose is subject to a system of control in which the 'controller', GS, is in turn controlled by GK. In contrast, in skeletal muscle, the control of glycogen synthesis is shared between glucose transport and GS. The characteristics of the two pairs of isoenzymes, liver GS/GK and muscle GS/HK I, and the relationships that they establish are tailored to suit specific metabolic roles of the tissues in which they are expressed. The key enzymes in glycogen metabolism change their intracellular localization in response to glucose. The changes in the intracellular distribution of liver GS and GK triggered by glucose correlate with stimulation of glycogen synthesis. The translocation of GS, which constitutes an additional mechanism of control, causes the orderly deposition of hepatic glycogen and probably represents a functional advantage in the metabolism of the polysaccharide.
Ferrer
Juan C
JC
Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, 08028 Barcelona, Spain.
Favre
Cristián
C
Gomis
Roger R
RR
Fernández-Novell
Josep M
JM
García-Rocha
Mar
M
de la Iglesia
Núria
N
Cid
Emili
E
Guinovart
Joan J
JJ
D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D019298:Glucose-6-Phosphate / Q000378:metabolism; D006006:Glycogen Synthase / Q000737:chemistry / Q000378:metabolism; D022781:Hepatocytes / Q000201:enzymology; D006593:Hexokinase / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism*; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000201:enzymology
D007527:Isoenzymes; D008112:Liver Glycogen; D019298:Glucose-6-Phosphate; D006006:Glycogen Synthase; D006593:Hexokinase; D005941:Glucokinase; D005947:Glucose