GLYCOGENOLYSIS | GLYCOGEN METABOLISM

GLYCOGENOLYSIS

In this blog we talked about glycogenolysis or glycogen metabolism. 

The degradation of stored glycogen in liver and muscle constitutes glycogenolysis. The pathways for the synthesis and degradation of glycogen are not reversible. An independent set of enzymes present in the cytosol carry out glycogenolysis. Glycogen is degraded by breaking -1,4- and -1,6-glycosidic bonds.

1. Action of glycogen phosphorylase : The - 1,4-glycosidic bonds (from the non-reducing ends) are cleaved sequentially by the enzyme glycogen phosphorylase to yield glucose 1-phosphate. This process—called phospho- rolysis—continues until four glucose residues remain on either side of branching point (-1,6- glycosidic link). The glycogen so formed is known as limit dextrin which cannot be further degraded by phosphorylase. Glycogen phosphorylase possesses a molecule of pyridoxal phosphate, covalently bound to the enzyme.

2. Action of debranching enzyme : The branches of glycogen are cleaved by two enzyme activities present on a single polypeptide called debranching enzyme, hence it is a bifunctional enzyme. Glycosyl 4 : 4 transferase (oligo -1,4 1,4 glucan transferase) activity removes a fragment of three or four glucose residues attached at a branch and transfers them to another chain. Here, one -1,4-bond is cleaved and the same -1,4 bond is made, but the places are different.  Amylo -1,6-glucosidase breaks the -1,6 bond at the branch with a single glucose residue and releases a free glucose.  The remaining molecule of glycogen is again available for the action of phosphorylase and debranching enzyme to repeat the reactions stated in 1 and 2.

3. Formation of glucose 6-phosphate and glucose : Through the combined action of glycogen phosphorylase and debranching enzyme, glucose 1-phosphate and free glucose in a ratio of 8 : 1 are produced. Glucose 1-phosphate is converted to glucose 6-phosphate by the enzyme phosphoglucomutase.

The fate of glucose 6-phosphate depends on the tissue. The liver, kidney and intestine contain the enzyme glucose 6-phosphatase that cleaves glucose 6-phosphate to glucose. This enzyme is absent in muscle and brain, hence free glucose cannot be produced from glucose 6-phosphate in these tissues. Therefore, liver is the major glycogen storage organ to provide glucose into the circulation to be utilised by various tissues.

In the peripheral tissues, glucose 6-phosphate produced by glycogenolysis will be used for glycolysis. It may be noted that though glucose 6-phosphatase is absent in muscle, some amount of free glucose (8-10% of glycogen) is produced in glycogenolysis due to the action of debranching enzyme (-1,6-glucosidase activity).

Glycogenolysis

GLYCOGENESIS

GLYCOGENESIS

The synthesis of glycogen from glucose is glycogenesis . Glycogenesis takes place in the cytosol and requires ATP and UTP, besides glucose.

1. Synthesis of UDP-glucose : The enzymes hexokinase (in muscle) and glucokinase (in liver) convert glucose to glucose 6-phosphate. Phosphoglucomutase catalyses the conversion of glucose 6-phosphate to glucose 1-phosphate. Uridine diphosphate glucose (UDPG) is synthesized from glucose 1-phosphate and UTP by UDP-glucose pyrophosphorylase.

2. Requirement of primer to initiate glycogenesis : A small fragment of pre-existing glycogen must act as a ‘primer’ to initiate glycogen synthesis. It is recently found that in the absence of glycogen primer, a specific protein—namely ‘glycogenin’—can accept glucose from UDPG. The hydroxyl group of the amino acid tyrosine of glycogenin is the site at which the initial glucose unit is attached. The enzyme glycogen initiator synthase transfers the first molecule of glucose to glycogenin. Then glycogenin itself takes up a few glucose residues to form a fragment of primer which serves as an acceptor for the rest of the glucose molecules.

3. Glycogen synthesis by glycogen synthase : Glycogen synthase is responsible for the formation of 1,4-glycosidic linkages. This enzyme transfers the glucose from UDP-glucose to the non-reducing end of glycogen to form - 1,4 linkages.

4. Formation of branches in glycogen : Glycogen synthase can catalyse the synthesis of a linear unbranched molecule with 1,4 - glycosidic linkages. Glycogen, however, is a branched tree-like structure. The formation of branches is brought about by the action of a branching enzyme, namely glucosyl -4-6 transferase. (amylo 1,4 1,6 trans- glucosidase). This enzyme transfers a small fragment of five to eight glucose residues from the non-reducing end of glycogen chain (by breaking -1,4 linkages) to another glucose residue where it is linked by -1,6 bond. This leads to the formation of a new non-reducing end, besides the existing one. Glycogen is further elongated and branched, respectively, by the enzymes glycogen synthase and glucosyl 4-6 transferase.

The overall reaction of the glycogen synthesis for the addition of each glucose residue is

(Glucose)n + Glucose + 2ATP (Glucose)n+1 + 2 ADP + Pi

Of the two ATP utilized, one is required for the phosphorylation of glucose while the other is needed for conversion of UDP to UTP.

   GLYCOGEN SYNTHESIS 

GLYCOGENESIS

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