Mammalian Glycogen Metabolism Enzymology, Regulation, and Animal Models of Dysregulated Glycogen Metabolism

Abstract

Glycogen synthesis and degradation require several enzymes, with glycogen synthase and glycogen phosphorylase being key enzymes in elongating and shortening, respectively, glucose chains in the glycogen macromolecule. Complex, reciprocal regulation of glycogen synthase and glycogen phosphorylase controls the amount of glycogen. Mammalian glycogen metabolism has been studied most extensively in muscle and liver. In the muscle, glycogen serves as a fuel for contraction and as a storage depot for glucose removed postprandially from the circulation. In the liver, glycogen is synthesized to remove excess postprandial glucose from the bloodstream and subsequently degraded during times of fasting to provide glucose to the body. Glycogen metabolism has also been studied to a lesser degree in other tissues, notably heart and kidney, and especially of late, the brain. The author has focused primarily on mammalian glycogen metabolism in muscle, liver, and brain. In addition to discussion of the enzymology and regulation of glycogen metabolism, select glycogen storage diseases are discussed, focusing on those where glycogen synthesis has been modulated in animal models of the disease.