Mechanism of palmityl coenzyme A inhibition of liver glycogen synthase.
Palmityl-CoA inhibits free liver glycogen synthase; the concentration required for half-maximum inhibition is 3 to 4 micrometer. Almost complete inhibition was observed at 50 micrometer. Palmityl-CoA inhibition is associated with dissociation of the tetrameric enzyme into monomers, and binding of palmityl-CoA to the monomers. Glycogen-bound enzyme is also inhibited by palmityl-CoA, resulting in dissociation of the enzyme into monomers and concomitant release of the enzyme from the primer glycogen. Palmityl-CoA inhibition of the enzyme is partially reversed by the glycogen synthase activator, glucose-6-P, whereas sodium lauryl sulfate-inhibited enzyme is not reactivated by glucose-6-P. Sodium lauryl sulfate inhibition results in the dissociation of the tetramer into the monomers. Bovine serum albumin and cyclodextrin can prevent palmityl-CoA inhibition only when they are added prior to palmityl-CoA addition. The possible physiological role of palmityl-CoA in glucose homeostasis is discussed.
D000214:Acyl Coenzyme A / Q000494:pharmacology*; D000818:Animals; D005958:Glucosephosphates / Q000494:pharmacology; D006006:Glycogen Synthase / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D046911:Macromolecular Substances; D008297:Male; D010171:Palmitoyl Coenzyme A / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D000214:Acyl Coenzyme A; D005958:Glucosephosphates; D046911:Macromolecular Substances; D010171:Palmitoyl Coenzyme A; D006006:Glycogen Synthase