Glycogen Metabolism

Hi, in this post we'll be discussing the ways in which glycogen is broken down and produced in the body. I'll describe the functions of glycogenesis and glycogenolysis and where is the body these processes can be found. We'll also cover the coordinated regulation of glycogen synthase and glycogen phosphorylase enzymes as well as discuss the metabolic roles of liver and muscle glycogen. In addition, I'll list the main actions of insulin, glucagon and adrenaline in carbohydrate metabolism.

The Function of Glycogen Stores

Firstly, glycogen is the major carbohydrate store in animals and is a polysaccharide consisting of many glucose monosaccharide units joined together. It is located in the cytosol of all tissues but is found mainly in the liver and muscle.

The Structure of a Glycogen Molecule

There are two main storage sites for glycogen: the liver and muscle.

Liver: 

The liver is responsible for the storage and export of glucose and thus works to maintain blood glucose concentrations. Liver glycogen stores are essential for glucose homeostasis and are used during short term starvation. These stores become depleted after 12-18 hours of fasting.

Muscle:

The function of muscle glycogen stores is to fuel glycolysis within the muscle only. These stores become depleted through prolonged vigorous exercise. They are not essential for glucose homeostasis and are instead used for high intensity exercise. These glycogen stores can only be used in the muscle because the muscle doesn't express the glucose-6-phosphatase enzyme. This enzyme cleaves the phosphate molecule that prevents glucose from exiting the cell. Thus without this enzyme, glucose cannot be exported from muscle glycogen stores. This is a useful feature of muscle glycogen stores because it means that the stores cannot be used up during starvation. This allows some fuel for anaerobic respiration during sprinting which allows the animal to catch food or avoid predators. In addition, muscles don't have receptors for glucagon which is released during starvation, this means that these stores can't be used for glucose homeostasis. 

Glycogenesis and Glycogenolysis

Glycogen is synthesised and broken down by different pathways. 

• Glycogenesis: is the synthesis of glycogen, it occurs when the glucose supply is in excess (after a meal). Glucose-6-Phosphate is gradually converted to a-1,4 and a1-6- glycogen by a series of enzymes. The enzyme glycogen synthase is the rate limiting enzyme.
• Glycogenolysis: this is the breakdown of glycogen. In the liver is occurs when blood glucose concentrations are low, this helps to maintain glucose homeostasis. In muscle it is used for ATP production during exercise. An a-1,6 glycogen branch and an a-1,4 glycogen branch are gradually converted to glucose-6-phosphate by a series of enzymes. The enzyme glycogen phosphorylase is rate limiting.Glycogenolysis yields 3 ATP molecules per glucose-6-phosphate that is produced. This is because the glucose-6-phosphate can be fed into glycolysis without the need of the hexokinase step which requires the input of one ATP.

Regulation:

Once again, cAMP dependent protein kinase plays an important role in regulating a biochemical pathway. When glucagon or adrenaline bind to their receptors on the surface of a cell they stimulate adenylate cyclase which converts ATP to cAMP. This stimulates cAMP dependent protein kinase which goes on to phosphorylate many other enzymes. It phosphorylates phosphorylase kinase which activates this enzyme and causes it to phosphorylate glycogen phosphorylase which causes it to become activated. Glycogen phosphorylase catalyses the conversion of glycogen to glucose-1-phosphate and thus initiates glycogenolysis. Glycogen phosphorylase found in the liver is an allosteric enzyme and is inhibited by glucose and ATP. When glucose binds to an active liver glycogen phsophorylase it will be inactivated, blocking glycogen breakdown when glucose accumulates faster than needed.

cAMP dependent protein kinase also phosphorylates glycogen synthase (which catalyses the conversion of UDP-glucose to glycogen), but this causes the molecule to be deactivated. Thus, glycogenesis is inhibited when glucagon or adrenaline are bound to the surface of the cell. 

cAMP dependent protein kinase also activates an inhibitor molecule by phosphorylating it. This inhibitor deactivates an enzyme called protein phosphatase-1. Protein phosphatase-1 removes the phosphate group from glycogen synthase, phosphorylase kinase and glycogen phosphorylase. Thus, when this molecule is inactivated glycogenesis does not occur and glycogenolysis occurs.

Overall, glucagon and adrenaline cause the net breakdown of glycogen.

Muscle Contraction and Glycogen Metabolism:

As explained in a previous post, when muscle contracts, the amount of Ca2+ in the cytoplasm of the cell increases. Ca2+ activates the calmodulin component of phosphorylase kinase causing it to phosphorylate and activate glycogen phosphorylase. Glycogen phosphorylase starts glycogenolysis. Ca2+ also stimulates calmodulin dependent protein kinase which phosphorylates and deactivates glycogen synthase, thus preventing glycogenesis. Overall, muscle contraction causes nett glycogen breakdown.

Insulin and Muscle Contraction:

Insulin is released when the animal has just eaten. When insulin binds to the receptors on the surface of a cell it causes cAMP to be converted to 5'-AMP by phosphodiesterase. This removes the cAMP stimulus from cAMP dependent protein kinase which prevents it from phosphorylating all the other enzymes which were mentioned above. Protein phosphatase-1 is also no longer inhibited, allowing the enzyme to remove phosphate groups from phosphorylase kinase, and glycogen phosphorylase. This means that glycogen synthase remains activated and thus glycogen can be synthesised and glycogenesis is initiated. In addition, the binding of insulin causes the activation of insulin sensitive protein phosphatase which removes the phosphate group from glycogen synthase causing it to be activated. Insulin also causes GLUT4 receptors to bring more glucose into the cell. The glucose is converted to glucose-6-phosphate which also activates glycogen synthase, causing glycogenesis to occur. Overall, insulin causes net glycogen synthesis.

That's it for this post, if you have any questions please feel free to ask in the comments section below :)