Glycogen & Glycogenolysis – MCAT Biochemistry | MedSchoolCoach

Glycogen & Glycogenolysis

MCAT Biochemistry Chapter 5 - Section 2.1 - Metabolic Pathways - Glycogen & Glycogenolysis

Sample MCAT Question - Glycogen & Glycogenolysis

Glycogen branches are attached to linear glycogen chains by which type of bond?

a) α-1,4 linkages

b) α-1,5 linkages

c) α-1,6 linkages

d) α-1,7 linkages

C is correct. α-1,6 linkages.

Glycogen has a branched structure that allows for rapid mobilization and breakdown of glucose molecules. The straight chains in glycogen are held together by α-1,4 linkages, while the branches are formed from α-1,6 linkages. Answer choices B and D are incorrect because glycogen does not form these types of linkages. Moreover, glucose is a six carbon and, therefore, cannot have 1,7 linkages.

Glycogen Overview

Glycogen is a glucose polymer that can be readily synthesized and broken down to release glucose for ATP production. Together, these processes are known as glycogen metabolism. This post is the first of two posts on glycogen and glycogen metabolism. In this post, we’ll cover glycogen’s structure and function, as well as glycogenolysis, the process by which glycogen chains are broken down into glucose monomers. Then in the second post, we’ll cover glycogenesis, the process by which glycogen is synthesized from glucose, as well as the hormonal regulation of these pathways.

Glycogen Structure and Function

Figure 1 shows the structure of glycogen. It has many branches made up of glucose molecules. This multibranched structure allows for the rapid mobilization of glucose, as free glucose molecules can be broken off of the branches and quickly transported to places of need. Several linkages hold the glucose monomers that make up glycogen together. Straight chain regions of glycogen consist of glucose monomers held together by α-1,4 linkages, while the branching points of glycogen are held together by α-1,6 linkages.

Glycogen's Branched Structure - MCAT Biochemistry
Figure 1. Glycogen's Branched Structure

Glycogen is primarily stored in liver and skeletal muscle cells. As a result of its branched polymer structure, glycogen can store large quantities of glucose in cells without affecting cellular osmolarity. For example, in a hepatocyte, or liver cell, if glucose were not stored as glycogen, the glucose concentration would be about 0.4 M. This concentration is considerably large for a single cell. However, when glucose is stored as glycogen, its concentration is approximately .01 μM, which is much more reasonable for a single cell.

Glycogenolysis

Glycogenolysis is the process of breaking down glycogen into glucose monomers. This process involves several steps. Figure 2 shows the reaction catalyzed by the enzyme glycogen phosphorylase, the first enzyme involved in glycogenolysis. As a phosphorylase enzyme, glycogen phosphorylase uses an inorganic phosphate to break the α-1,4 linkages in glycogen, freeing glucose-1-phosphate molecules.

Glycogen Phosphorylase in Glycogenolysis - MCAT Biochemistry
Figure 2. Glycogen Phosphorylase in Glycogenolysis

Phosphoglucomutase then converts glucose-1-phosphate into glucose 6-phosphate. In hepatocytes, glucose-6-phosphate can then be converted to glucose by glucose-6-phosphatase and released into the bloodstream to regulate and maintain glucose levels. Skeletal muscles, on the other hand, lack the enzyme glucose-6-phosphatase, and therefore cannot release glucose into the body. The reason for this is because skeletal muscle cells are storing glycogen for their own use, therefore, the glucose-6-phosphate formed feeds directly into glycolysis.

Branch Point Degradation

Once four glucose molecules are left on a glycogen branch, glycogen phosphorylase can no longer break off glucose-1-phosphate monomers. Instead, debranching enzyme takes over (Figure 3). The debranching enzyme has two main functions: A transferase function and a glucosidase function. In terms of its transferase function, the debranching enzyme will transfer a segment of three glucose residues from an α-1,6 branch onto a nearby branch of the glycogen chain. Then functioning as a glucosidase, it will cleave the α-1,6 linkage holding the single remaining glucose molecule, producing a free glucose molecule. Glycogen phosphorylase will then continue breaking apart the extended branch as needed.

Glycogen Phosphorylase and Debranching Enzyme in Glycogenolysis - MCAT Biochemistry
Figure 3. Glycogen Phosphorylase and Debranching Enzyme in Glycogenolysis

If you found this article useful, check out this post which covers glycogenesis (the process by which glycogen polymers are synthesized from glucose monomers) as well as the hormonal regulation of glycogen-related pathways.

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