Glycogenesis Occurs Mainly in Muscle & Liver
المؤلف:
Peter J. Kennelly, Kathleen M. Botham, Owen P. McGuinness, Victor W. Rodwell, P. Anthony Weil
المصدر:
Harpers Illustrated Biochemistry
الجزء والصفحة:
32nd edition.p173
2025-06-26
397
Glycogen Biosynthesis Involves UDP-Glucose
As in glycolysis, glucose is phosphorylated to glucose-6-phosphate, catalyzed by hexokinase in muscle and glucokinase in liver (Figure 1). Glucose-6-phosphate is isomerized to glucose-1-phosphate by phosphoglucomutase. The enzyme itself is phosphorylated, and the phosphate group takes part in a reversible reaction in which glucose 1,6-bisphosphate is an intermediate. Next, glucose-1-phosphate reacts with uridine tri phosphate (UTP) to form the active nucleotide uridine diphosphate glucose (UDPGlc) and pyrophosphate (Figure 2), catalyzed by UDPGlc pyrophosphorylase. The reaction proceeds in the direction of UDPGlc formation because pyrophosphatase catalyzes hydrolysis of pyrophosphate to 2× phosphate, so removing one of the reaction products. UDPGlc pyrophosphorylase has a low Km for glucose-1-phosphate and is present in relatively large amounts, so that it is not a regulatory step in glycogen synthesis.
Fig1. Pathways of glycogenesis and glycogenolysis in the liver. ( , ⊕ stimulation; ⊖, inhibition.) Insulin decreases the level of cAMP only after it has been raised by glucagon or epinephrine; that is, it antagonizes their action. Glucagon acts on heart muscle but not on skeletal muscle. *Glucan transferase and debranching enzyme appear to be two separate activities of the same enzyme.
Fig2. Uridine diphosphate glucose (UDPGlc).
The initial steps in glycogen synthesis involve the protein glycogenin, a 37-kDa protein that is glucosylated on a specific tyrosine residue by UDPGlc. Glycogenin catalyzes the trans fer of a further seven glucose residues from UDPGlc, in 1 → 4 linkage, to form a glycogen primer that is the substrate for glycogen synthase. The glycogenin remains at the core of the glycogen granule (see Figure 15–12). It is believed that the self glycosylation of glycogen and the oligosaccharide primer that results is required for glycogen synthesis to occur. One genetic report of a defect in this gene (GSD-IV) primarily impairs heart function. Glycogen synthase catalyzes the formation of a glycoside bond between C-1 of the glucose of UDPGlc and C-4 of a terminal glucose residue of glycogen, liberating UDP. The addition of a glucose residue to a preexisting glycogen chain, or “primer,” occurs at the nonreducing, outer end of the molecule, so that the branches of the glycogen molecule become elongated as successive 1 → 4 linkages are formed (Figure 3).
Fig3. The biosynthesis of glycogen. The mechanism of branching as revealed by feeding 14C-labeled glucose and examining liver glycogen at intervals.
Branching Involves Detachment of Existing Glycogen Chains
When a growing chain is at least 11 glucose residues long, branching enzyme transfers a part of the 1 → 4 chain (at least six glucose residues) to a neighboring chain to form a 1 → 6 linkage, establishing a branch point. The branches grow by further additions of 1 → 4-glucosyl units and further branching.
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