The Metabolism of Glycogen in Animals:- Glucose 1-Phosphate Can Enter Glycolysis or, in Liver, Replenish Blood Glucose
Glucose 1-phosphate, the end product of the glycogen phosphorylase reaction, is converted to glucose 6-phosphate by phosphoglucomutase, which catalyzes the reversible reaction
Glucose 1-phosphate ⇌glucose 6-phosphate , Initially phosphorylated at a Ser residue, the enzyme donates a phosphoryl group to C-6 of the substrate, then accepts a phosphoryl group from C-1 (Fig. 15–5). The glucose 6-phosphate formed from glycogen in skeletal muscle can enter glycolysis and serve as an en ergy source to support muscle contraction. In liver, glycogen breakdown serves a different purpose: to re lease glucose into the blood when the blood glucose level drops, as it does between meals. This requires an enzyme, glucose 6-phosphatase, that is present in liver and kidney but not in other tissues. The enzyme is an integral membrane protein of the endoplasmic reticulum, predicted to contain nine transmembrane helices, with its active site on the lumenal side of the ER. Glucose 6-phosphate formed in the cytosol is transported into the ER lumen by a specific transporter (T1) (Fig. 15–6) and hydrolyzed at the lumenal surface by the glucose 6-phosphatase. The resulting Pi and glucose are thought to be carried back into the cytosol by two different transporters (T2 and T3), and the glucose leaves
FIGURE 15–5 Reaction catalyzed by phosphoglucomutase. The reaction begins with the enzyme phosphorylated on a Ser residue. In step 1, the enzyme donates its phosphoryl group (green) to glucose 1-phosphate, producing glucose 1,6-bisphosphate. In step 2, the phosphoryl group at C-1 of glucose 1,6-bisphosphate (red) is transferred back to the enzyme, re-forming the phosphoenzyme and producing glucose 6-phosphate.
FIGURE 15–6 Hydrolysis of glucose 6-phosphate by glucose 6 phosphatase of the ER. The catalytic site of glucose 6-phosphatase faces the lumen of the ER. A glucose 6-phosphate (G6P) transporter (T1) carries the substrate from the cytosol to the lumen, and the products glucose and Pi pass to the cytosol on specific transporters (T2 and T3). Glucose leaves the cell via the GLUT2 transporter in the plasma membrane.
the hepatocyte via yet another transporter in the plasma membrane (GLUT2). Notice that by having the active site of glucose 6-phosphatase inside the ER lumen, the cell separates this reaction from the process of glycolysis, which takes place in the cytosol and would be aborted by the action of glucose 6-phosphatase. Genetic defects in either glucose 6-phosphatase or T1 lead to serious derangement of glycogen metabolism, resulting in type Ia glycogen storage disease (Box 15–1). Because muscle and adipose tissue lack glucose 6-phosphatase, they cannot convert the glucose 6 phosphate formed by glycogen breakdown to glucose, and these tissues therefore do not contribute glucose to the blood.
