MCAT Biochemistry
Glycogen is a large branched polysaccharide that functions as the main storage form of glucose and serves as a fuel reserve during the early stages of fasting. It is made, stored, and broken down in the liver and skeletal muscle within the cytosol. Glycogen synthesis begins with glucose, which is converted to glucose-6-phosphate (G6P) by either hexokinase or glucokinase in an irreversible reaction. Phosphoglucomutase then transforms G6P to glucose-1-phosphate (G1P), and UDP glucose pyrophosphorylase uses UTP to turn G1P into UDP glucose. Glycogenin creates a short non-branched glycogen primer from several UDP glucose molecules, followed by glycogen synthase, which links glucose monomers via alpha-1,4 glycosidic linkages. Glycogen branching enzyme then removes alpha-1,4 linkages from approximately every seventh glucose residue and creates alpha-1, 6 branches to condense glycogen.
Glycogenolysis is the process of breaking down glycogen. Glycogen phosphorylase catalyzes the rate-limiting step of removing G1P residues from branched glycogen until four glucose residues are left on a branch. Two debranching enzymes, 4-alpha-D-glucanotransferase and alpha-1,6-glucosidase, assist in the degradation of glycogen. Phosphoglucomutase turns the remaining G1P back into G6P, and glucose-6-phosphatase removes the phosphate group from G6P, producing glucose.
Lesson Outline
<ul> <li>Glycogen serves as a fuel reserve during the early stages of fasting.</li> <li>Main storage form of glucose found in liver and skeletal muscle.</li> <li>Glycogen synthesis and degradation take place in the cytosol.</li> <li>Hexokinase and glucokinase initiate glycogen synthesis by making glucose-6-phosphate (G6P).</li> <ul> <li>Hexokinase: present in brain, skeletal muscle, and all other tissues except the liver and pancreatic beta cells.</li> <li>Glucokinase: present in liver and pancreatic beta cells, serves as a glucose sensor.</li> </ul> <li>Glycogen synthesis steps:</li> <ul> <li>G6P is converted to glucose-1-phosphate (G1P) by phosphoglucomutase.</li> <li>UDP-glucose pyrophosphorylase uses UTP to turn G1P into UDP-glucose.</li> <li>Glycogenin creates a short non-branched glycogen primer from several UDP-glucose molecules.</li> <li>Glycogen synthase links glucose monomers via alpha-1,4 glycosidic linkages, insulin activates it, and glucagon inhibits it.</li> <li>Glycogen branching enzyme creates alpha-1,6 branches to condense glycogen.</li> </ul> <li>Glycogen degradation (glycogenolysis) steps:</li> <ul> <li>Glycogen phosphorylase removes G1P residues from branched glycogen, glucagon activates it, and insulin inhibits it.</li> <li>Two debranching enzymes remove remaining glucose residues from branch points.</li> <li>Phosphoglucomutase turns G1P back into G6P.</li> <li>Glucose-6-phosphatase removes the phosphate from G6P to make glucose, only present in the liver.</li> </ul> </ul>
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FAQs
Glycogen synthesis is the process by which glucose molecules are combined to form glycogen, the primary storage form of glucose in animals. Glycogenolysis, on the other hand, is the process of breaking down glycogen into glucose-1-phosphate (which is then converted to glucose-6-phosphate) to provide energy when required by cells, particularly in muscles and the liver.
Glucose-6-phosphate (G6P) plays a crucial role in both glycogen synthesis and glycogenolysis. In glycogen synthesis, G6P is converted to glucose-1-phosphate, which is subsequently converted to uridine diphosphate glucose (UDPG), the activated form of glucose required for glycogen synthesis. In glycogenolysis, the breakdown of glycogen yields G6P, which can then be either converted to glucose for release into the bloodstream or metabolized to generate ATP via glycolysis or the pentose phosphate pathway.
Glycogen storage serves as a readily available energy source for the body, particularly during periods of fasting, intense physical activity, or when blood glucose levels are low. Glycogen is mainly stored in the liver and muscles, with the liver regulating blood glucose levels by breaking down glycogen into glucose-6-phosphate and subsequently into glucose, while muscles primarily utilize glycogen to fuel muscle contractions during exercise or other high-energy demands.
The glycogen branching enzyme is responsible for creating the highly branched structure of glycogen, which is essential for its rapid synthesis and degradation. By adding α(1→6) linkages to the linear α(1→4) linked glucose chains at regular intervals, the enzyme generates numerous terminal points for glycogen synthesis (by glycogen synthase) and glycogenolysis (by glycogen phosphorylase) to occur simultaneously. This branched structure not only increases glycogen's solubility but also allows for rapid release of glucose molecules when energy is needed by cells.
Several factors can regulate the balance between glycogen synthesis and glycogenolysis, including hormonal levels, enzyme activities, and energy needs. Insulin, a hormone released in response to high blood glucose, promotes glycogen synthesis, whereas glucagon and epinephrine, released during periods of stress or low blood glucose, stimulate glycogenolysis. Additionally, the activities of glycogen synthase (for synthesis) and glycogen phosphorylase (for glycogenolysis) are regulated by various allosteric effectors and post-translational modifications, ensuring that the balance between these two processes meets the body's energy needs effectively.
