Ahern's BB 350 at OSU - 28. Glycogen Metabolism

1. Contact - [email protected] 2. Kevin's lectures with The Great Courses - https://www.thegreatcoursesplus.com/b... 3. Kevin's Lecturio videos for medical students - https://www.lecturio.com/medical-cour... 4. Course materials at https://kevingahern.com/biochemistry-... 5. Course video channel at    • Ahern's BB 350 at OSU - 1. Introduction   6. Metabolic Melodies at https://teeheetime.com/category/lyric... 7. Kevin's Free Biochemistry books - https://kevingahern.com/biochemistry-... 8. Kevin's Pre-med Audio course on Listenable - https://listenable.io/web/courses/143... 1. The Cori Cycle allows muscles to export lactate to the bloodstream. From there it goes to the liver, where gluconeogenesis acts to convert it to glucose. Glucose is dumped back into the blood where it arrives in the muscles and is used to continue the production of ATP. 2. Pyruvate kinase is the only enzyme of glycolysis that is regulated by both phosphorylation and allosteric means. Phosphorylation makes it less active, whereas dephosphorylation makes it more active. Allosterically, ATP and alanine inhibit it andF1,6BP activates it. 3. The pentose phosphate pathway is the cell's primary source of NADPH, ribose-5-phosphate (for nucleotide biosynthesis), and it is a way for cells to interchange sugars. 4. Fermentation occurs when cells run out of oxygen. Oxidation of glucose in the absence of oxygen is about 1/19th as efficient as it is in the presence of oxygen. Fermentation occurs in all cells to regenerate NAD+. Animal cells convert pyruvate to lactate and bacteria/yeast convert pyruvate to ethanol. Glycogen Metabolism 1. Breakdown of glycogen is catalyzed by glycogen phosphorylase . In the phosphorolysis reaction, phosphate is used to break one glucose unit from glycogen, forming glucose-1-phosphate (G1P). The advantage of phosphorolysis is that a phosphate is attached to glucose without requiring ATP. G1P can readily be converted to G6P by phosphoglucomutase and used in glycolysis. Thus, G1P from glycogen can be used to generate cellular energy VERY fast. 2. The enzyme does not work well close to the 1,6 branches of glycogen, so Debranching Enzyme is used to move glucoses from a branch to a linear chain and make them available to the phosphorylase. Debranching moves all but one of the glucoses on the side chain. The last one, which is in a 1,6 configuration, is released as free glucose. 3. Glycogen synthesis uses energy ultimately from UTP . In this reaction, glucose is "activated" by being attached to UDP to form UDP-glucose (UDPG). 4. Glycogen synthase catalyzes the addition of a glucose to the end of a glycogen molecule from a UDP-glucose. Branching enzyme creates the alpha1,6 linkages of glycogen. 5. When glucose is needed quickly in an emergency, the hormone epinephrine (adrenalin) is released into the bloodstream. It binds to cells and stimulates the phosphorylation of enzymes (including glycogen phosphorylase and glycogen synthase). Phosphorylation has opposite effects on these two enzymes. Glycogen phosphorylase is activated by phosphorylation, but glycogen synthase is inhbited by phosphorylation. 6.The hormone system works within seconds, but since it must travel through the bloodstream, it is not as rapid as the response that can be obtained allosterically. This is important in muscle cells when they must VERY quickly act. ATP levels can fall very rapidly and the cells very quickly want to turn on glycogen breakdown. Allosteric controls work on both the phosphorylated and dephosphorylated forms of the enzyme. 7. For the dephosphorylated enzyme, AMP converts it from the T form into the A form and either ATP or G6P convert the R form into the T form. AMP indicates low energy, so the enyzme is ACTIVATED then and glycogen is broken down to release G1P, which can be converted to G6P and enter glycolysis. For the phosphorylated form of the enzyme, glucose can convert the enzyme from the R to the T state (shutting it down), but if glucose is not present, the enzyme will flip automatically into the R state. This is why we consider the phosphorylated form of the enzyme more active - it is much more easily activated to the R state.