BHS 150.1 – Biochemistry II Notetaker: Kim Powell Date: 2/1/2013, 2sndhalf Page1 start on pg. 263 REVIEW: Insulin is present after a meal; goal is to store nutrients insulin works through receptor tyrosine kinase ◦ receptor tyrosine kinase phosphorylates a phosphatase ◦ phosphatase removes phosphate group from glycogen synthetase, glycogen phosphorylase, and pyruvate kinase ▪ ***both pyruvate kinase and glycogen synthetase are activated when de-phosphorylated. Glycogen phosphorylase is inhibited when dephosphorylated. Glucagon works through metabotropic receptor ◦ G-protein stimulates adenylate cyclase to make cAMP and activate a family of protein kinases FOCUS ON THREE ENZYMES: glycogen synthease, glycogen phosphorylase, and pyruvate kinase: Glycogen Synthetase Fed State (insulin high and glucagon low) Glyocogen Phosphorylase ACTIVATED/ glycogen INACTIVATED/ production stimulated glycogen degradation inhibited Fasting State (glucagon INACTIVATED/ high and insulin low) glycogen production inhibited Pyruvate Kinase ACTIVATED/glycolysis stimulated ACTIVATED/ glycogen INACTIVATED/ degradation stimulated glycolysis inhibited FED STATE (postprandial state): Glucose (from carbohydrates) Glucokinase traps glucose liver provides itself energy through the kreb's cycle and electron transport chain starts to make glycogen Muscle Brain Liver RBCs Other tissue Amino acids (from proteins) Fatty acids Used to make proteins As glycogen synthetase enzyme becomes saturated, production of triglycerides is stimulated; lots of acetl CoA/malonyl CoA present Muscle can use glucose for energy or and store excess as glycogen Muscle takes up amino acids to repair muscles after exercise Muscle can use fatty acids for energy Brain prefers glucose as its energy source, lots of glucose goes to the brain Used to make proteins neurotransmitte rs Aren't used by brain during fed state brain is insulinindependent RBC can ONLY use glucose for energy Aren't used by RBCs exclusively anaerobic glycolysis produces lactate which gets sent to the liver for glucoeogenesis Can use glucose right after eating but they use a variety- aren't Can use fatty acids but they use a variety- Use amino acids to make neurotransmitte very picky rs aren't very picky Adipos e tissue Most fats are put into storage in adipose tissue ◦ dietary are delivered from chylomicron ◦ triglycerides from liver are delivered via VLDL FASTING STATE: Glucose (from carbohydrates) Liver Glycogen broken down into glucose so that brain and RBC can get glucose Used in gluconeogenesis Fatty acids Liver uses fatty acids to make ketone bodies ketone bodies made from acetyl coA (can be used by muscle but NOT by liver) when it runs out of glycogen, it starts gluconeogenesis using lactate from RBCs, glycerol from fatty acid breakdown, and amino acids from muscles Insulin is gone, can't take up glucose they use their stores of glycogen Brain Uses glucose from quick store of glycogen RBCs RBC can ONLY use glucose for energy exclusively anaerobic Muscl e Amino acids (from proteins) ◦ 3-hydroxybutyrate ◦ acetone (breathedoff) Proteins are broken down to provide amino acids for liver to do gluconeogenesis Uses fatty acids as primary fuel source also use 3 hydroxybutyrate made by liver (using an enzyme to break them back into acetyl coA Not being used for energy Not being used for energy Aren't used by RBCs glycolysis produces lactate which gets sent to the liver for glucoeogenesis Other tissue Aren't using glucose because insulin isn't present Adipo se tissue Starts to break down to release triglycerides into bloodstream Kidney excretes urea when amino acids are broken down Can use fatty acids but they use a varietyaren't very picky ◦ Starts releasing triglycerides (for muscle) STARVING STATE (2-3 days without food): Glucose (from carbohydrates) Liver Muscle Glucose levels are stability low glucagon levels aren't still rising, they have plateaued liver is glycogen depleted and it's using gluconeogensis using lactate and glycerol Depleted their glycogen stores Amino acids (from proteins) Fatty acids Less are available because muscle isn't being broken down Used almost exclusively to make ketone bodies to be fed to the brain Decrease in breakdown to protect heart and other important Being used predominantly by muscle muscles Brain RBCs Brain wants glucose but liver isn't providing it easily because muscles can't keep degrading and providing amino acids for gluconeogenesi s Still using glucose because they can't use anything else Not used for energy Not used for energy Adipose tissue Brain starts using ketone bodies; they become primary energy source ketone bodies are easier to extract acetyl coA from than fatty acids Not used for energy Degrade quickly to make fatty acids available for muscle and liver Diabetes vs. starving state: Uncontrolled diabetics are in “starvation” mode even though they have lots of glucose. ◦ Diabetes you have low insulin (same as starvation) but HIGH levels of glucose. The high levels of glucose cause damage ▪ lots of fatty acids= clogging arteries ▪ no insulin, can't store glucose, so glycogen stores are depleting and liver starts making glucose ▪ glycolysis isn't going on, so we aren't storing glucose as fatty acids. ▪ glucose is being excreted ▪ glucose damages the retina in 3 ways: absorption of water leads to macular edema neovascularization because vessel walls are being glycated lens swells, cornea swells ▪ nerves are glycated which leads to an increase in pain ▪ ketone bodies are still being made by the liver and leading to acidic problems and eventually ketoacidosis. CLICKER QUESTIONS: 1. Insulin binds to a receptor tyrosine kinase which: dephosphorylates the metabolic enzymes phosphorylates the metabolic enzymes phosphorylates another kinase to phosphorylate the metabolic enzymes phosphorylates a phosphatase that dephosphorylates the metabolic enzymes 2. During fasting, what are some of the sources of carbons for gluconeogenesis (choose 3): amino acids from protein degradation ketone bodies made by the liver glycerol from triglyceride breakdown glycogen from the liver stores lactate from glucose metabolism