Carbohydrate Metabolism 1

Detailed table of contents

This enzyme is confined to liver parenchymal cells which can secrete glucose into the bloodstream. It is located in the membrane of the endoplasmic reticulum with its active centre facing the luminal side. Accessory transport proteins are required to bring the substrate into the ER lumen and return the glucose to the remainder of the cell. An associated calcium binding protein probably plays a regulatory role.
Glucokinase phosphorylates glucose in the liver and is required for blood glucose homeostasis. Most peripheral tissues have hexokinase in place of glucokinase.

Glucokinase has a low affinity for glucose and must be rarely saturated with this substrate under physiological conditions. It serves to "cream off" surplus glucose from the hepatic portal blood, without making significant inroads into the normal arterial blood glucose pool. The glucokinase gene is only expressed in tissues such as  liver and pancreatic islets, where the cell membranes are freely permeable to glucose without any insulin requirement.

Insulin promotes the transcription of the liver glucokinase gene.
Glycogen phosphorylase uses inorganic phosphate to successively remove glucose-1-phosphate units from the non-reducing ends of glycogen molecules.

The liver enzyme plays a major role in blood glucose homeostasis. Glycogen breakdown in extra-hepatic tissues cannot contribute to blood glucose because these cells lack the ancillary enzymes and transport systems.

The liver enzyme responds strongly to glucagon and adrenalin. It is activated in response to increased 3'5'cyclic AMP by a phosphorylation cascade involving protein kinase A and phosphorylase kinase. In addition, phosphorylase kinase includes a calmodulin subunit and undergoes allosteric activation by calcium ions. Phosphorylase is directly activated by 5'AMP.
Glycogen synthetase adds additonal glucose monomers donated by UDP-glucose to the non-reducing ends of the glycogen primers.

The liver enzyme plays a major role in blood glucose homeostasis and is regulated coordinately with glycogen phosphorylase.

Glycogen synthetase is phosphorylated and de-activated by protein kinase A in response to increased 3'5'cyclic AMP. In addition it is subject to allosteric activation by glucose-6-phosphate and inhibition by calcium ions.