Ahern's Biochemistry #27 - Glycogen Metabolism III / Metabolic Melodies

Ahern's Biochemistry #27 - Glycogen Metabolism III / Metabolic Melodies

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 Biochemistry #1 - Aqueous Solution...   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... Highlights Glycogen III 1. PP-1 binds to a protein called GM (in muscle) or GL (in liver). Activation of PKA by epinephrine or glucagon causes GM to be phosphorylated, which, in turn, causes PP-1 to be released in a less active form. PKA also phosphorylates the PP-1 inhibitor, which then binds PP-1 and inactivates it. Thus, the phosphorylation system shuts down the dephosphorylation system and vice versa, depending on which hormone has bound to the cell surface receptor. 2. When bound to GL, PP-1 is held close to the glycogen phosphorylase, which is useful because this allows easy access to dephosphorylate it and turn it off. 3. GPa normally binds PP-1-GL tightly and acts as a glucose sensor in liver cells. PP-1 is inactive when bound to GPa if GPa is in the R state. Increasing glucose concentration causes GPa to flip into the T state. When GPa is in the T state, PP-1-GL is released from GPa, becomes active, and dephosphorylates GPa, forming GPb. Freed from GPa, can then PP-1 dephosphorylate GSb, forming GSa. Thus, glycogen synthesis is NOT activated until glycogen breakdown is first stopped. 9. Thus, the experiment I showed in class where addition of glucose to purified GPa and GSb causing conversion of GPa to GPb and GSb to GSa makes sense in that addition of glucose causes GPa to flip into the T state, which causes it to release PP-1-GL to begin dephosphorylation of the two enzymes.