Glycogenolysis - Biochemistry

When glycogen phosphorylase reaches a branching point in glycogen, the bonds switch from being alpha-1,4-glycosidic bonds to alpha-1,6-glycosidic bonds. It is unable to cleave these bonds, and so other enzymes (a transferase and a glucosidase) must come into play.

Glycogen is first debranched and broken down from its non-reducing end by glycogen phosphorylase to give the product G1P, which is then converted into G6P by phosphoglutomutase. Glycogen synthase, glycogen branching enzyme, and UDP-glucose pyrophosphorylase are required for glycogen synthesis.

In order to break down glycogen into individual glucose-6-phosphate units, all of the above enzymes are required. Each plays a specific role in one of the following activities: degradation of glycogen initially, remodeling of the glycogen so that it can be acted upon by the enzymes, and conversion of glucose-1-phosphate to glucose 6-phosphate.

Glycogen phosphorylase, the rate-limiting enzyme of glycogenolysis does not breaks alpha 1,6 glycosidic bonds. It releases glucose from glycogen by hydrolyzing alpha 1,4 glycosidic bonds until it reaches a branch point in the glycogen molecule. At this time, another enzyme, a debranching alpha 1,6 glycosidase hydrolyzes the alpha 1,6 glycosidic bonds. Glycogen phosphorylase is under regulation by many hormones, including insulin and glucagon, as well as epinephrine.

Glycogen is mostly stored in the liver and skeletal muscle. When it is broken down in the liver, the last enzyme, a phosphatase, removes the last phosphate group to release plain glucose into the bloodstream. In the muscle, there is no need to release the glucose, so glycogen is only broken down as far as glucose-6-phosphate. Skeletal muscle cells lack the last phosphatase required to remove the phosphate from carbon 6. This isn't an obstacle, however, because the glucose-6-phosphate is already on to the second stage of glycolysis.

Insulin is released in response to high blood glucose. It causes a signaling cascade that, in addition to other things, stops glycogenolysis. This is done by converting glycogen phosphorylase from it's active "a" form to its inactive "b" configuration. The "R" state is the active state, so the presence of glucose would not trigger the breakdown of glycogen. 5' AMP would not inhibit an inactive form of an enzyme. High AMP would mean a demand for ATP, so it would convert the enzyme to its "a" form.

Phosphorylation of glycogen phosphorylase activates it, converting it from its inactive B-form to its active A-form.

Phosphorolysis is the name given to the addition of phosphate across a bond. Remember that in glycogenolysis, glycogen phosphorylase adds a phosphate across the a-1,4-glycosidic bonds between the glucose units of glycogen. The result is that glucose leaves as glucose-1-phosphate. If hydrolysis were performed instead of phosphorolysis, free glucose would be severed from glycogen and would be able to leave the cell.

AMP is an activator of GP, whereas ATP is an inhibitor of GP. GP cleaves the alpha 1-4 glycosidic bond between a terminal glucose molecule and the rest of the glycogen straight chain, yielding glucose-1-phosphate during glycogenolysis.

The non reducing end of a glycogen branch is the end from which glucose units are removed during degradation of glycogen.

A catabolic reaction is defined as a reaction used to break down a large molecule into smaller subunits. Of the following options, glycogenolysis is the only option where a larger molecule (glycogen) is broken down into smaller subunits (individual glucose molecules).

Glycogen is the storage form of glucose, and is more readily accessible than starches or fats. It is used for short-term supply of glucose and in starvation conditions is used up in a matter of hours. It is mainly stored in the liver and skeletal muscle. Glycogenolysis in the liver results in glucose release into the bloodstream, whereas in the muscle the glucose is immediately used up. The highest demand for the glucose is in the muscle, and that is where most of it is stored.

When glycogen is broken down, the individual units that are removed are glucose-1-phosphate units. These are then transformed into glucose-6-phosphate molecules which are of extreme biological importance because of their ability to enter various different pathways. These pathways include glycolysis and the pentose phosphate pathway. The urea cycle, however, has to do with amino acids/proteins.