BHS 150.2 Biochemistry Notetaker: Laurel Hammang Date: 01/25/13, 1st hour Page1 Overview Integration of metabolism occurs in the liver Final 2 pathways: gluconeogenesis glycogen metabolism One function of liver: supply body with glucose Brain needs glucose constantly, works under insulin-independent mechanism >3-4 days, brain can use other fuel sources of glucose (starvation) RBCs need glucose supply for protection/ prevent damage After ingesting a meal, BG levels rise stored in liver as glycogen for short term energy broken down and released as needed when BS levels drop stored as fat tissue for longer term energy storage Glucagon increases when insulin levels decrease, vice versa Insulin works via a receptor tyrosine kinase mechanism Glucagon works via a metabotropic receptor mechanism Our bodies can store enough glycogen for 12 hours, after that, our bodies undergo gluconeogenesis: using other sources such as amino acids and carbs to produce new glucose if glucose levels fall too low Glycogen Metabolism Glycogen: storage form of glucose Made in muscle for muscle use only for quick energy; made in liver for remainder of body Made with primer: glycogenin Glucose molecules are linked together via alpha 1,4 glycosidic bonds When chain gets too long, an alpha 1,4 glycosidic bond is broken and a alpha 1,6 glycosidic bond so that the chain can be packed tightly and not increase osmotic pressure Glycogenesis: glycogen synthesis 1. Glucose is phosphorylated with hexokinase (muscle) or glucokinase (liver) Phosphate group traps the glucose inside the cell (glucose-6-phosphate) 2. Phosphoglucomutase is activated when high levels of G6P glycolysis pathway is moving too fast to keep up when there is so much G6P present, so this enzyme (a glycogen synthesis enzyme) is activated 3. Phosphoglucomutase converts G6Pī Glucose-1-P 4. UDP-Glucose Phosphorylase adds 2 phosphates and a uridine base to glucose to create high energy phosphate bond committed step** adds potential energy to glucose to make another bond 5. Glycogen synthetase transfers glucose from UDP and adds it to glycogen chain with an alpha 1,4 bond 6. Branching enzyme breaks an alpha 1,4 bond and creates an alpha 1,6 to create a new branch on long glycogen chain. This compacts the storage structure and decreases osmolarity Glycogenolysis: break down of glycogen 1. Glycogen phosphorylase breaks an alpha 1,4 bond and adds a phosphate to the glucose 2. Glucose at end becomes glucose 1-phosphate 3. Phosphoglucomutase converts G1P to G6P, which feeds into glycolysis *this would be the end of the pathway if this were in a muscle cell *If this were in the liver, the pathway would continue: 4. Glucose-6-phosphatase removes the phosphate from the glucose molecule when phosphate is attached, glucose is trapped inside the cell 5. Transferase breaks the alpha 1,4 bond of the branched chain and makes a new alpha 1,4 bond at the end of the long chain, leaving one single glucose where the branch was previously via alpha 1,6 bond This step must be done because the enzyme is too big to reach the last few bonds between the branched molecules 6. Debranching enzyme removes the last single-branched glucose from the chain by breaking the alpha 1,6 bond this frees the glucose molecule so it can be released into the bloodstream for energy Regulation Insulin levels are high when glucose levels are high Activates storage of glucose Activates a phosphatase (synthetase) Phosphatase: removes a phosphate group Glycogen synthetase stimulates glycogen synthesis when a phosphate group is added Glycogen phosphorylase is inactive when dephosphorylated *Adding a phosphate doesn’t always activate something Insulin levels are low when glucose levels are low Break down of glycogen is stimulated Activates a kinase (which adds a phosphate) Glycogen synthetase is inactive when phosphorylated Glycogen phosphorylase is activated when phophorylated Clicker Question: In human cells, glycogen is: Easily broken down to provide glucose residues and is the main storage form of glucose.