Metabolism P3

• Fasted State/Catabolic


  Period when nutrients are broken down and used for energy

  
• Fed State/Anabolic


  Period following a meal when nutrient absorption is underway

  
• Integration of Function


  • Metabolism
  • Insulin/Glucagon
• Final Chapter
• Metabolism


  • Fed vs Fasted
  • Overview
  • Fed State (Insulin)
  • Fasted State (Glucagon)
  • Balance
  • Pathophysiology
  • Pharmacology

  
• Metabolism


  Sum of all chemical and physical changes that occur in body tissues

  
• Metabolism


  1. Catabolism (catabolic reactions)

  2. Anabolism (anabolic reactions)
• Catabolism


  Catabolic Pathway: breaks larger/complex molecules into smaller ones
• Anabolism


  Anabolic Pathway: build smaller/simple molecules to synthesize larger molecules
• Nutrient pool


  All available nutrient molecules distributed in blood
• Body taps into stored reserves when amount of nutrients is low
• Cellular metabolism


  1. Organic molecules deposited into the cell after being broken down (Catabolic)

  2. Intracellular catabolic procedures to be deposited into a nutrient pool

  3. ATP production or anabolism to replace cellular components
• Fed State


  Primarily Anabolism
• Fasted State


  Primarily Catabolism
• Fed/Absorptive state


  Period following a meal when nutrient absorption is under way

  
• Fasted/Postabsorptive state


  Normal blood glucose levels are maintained, body relies on internal energy reserves
• Metabolic tissues


  • Liver
  • Adipose tissue
  • Skeletal muscle
  • Nervous tissue
  • Other peripheral tissues
• Liver


  • Focal point of metabolic regulation and control, great diversity of enzymes, significant energy reserves (glycogen deposits)
• Adipose tissue


  • Stores lipids, primarily as triglycerides
• Skeletal muscle


  • Substantial glycogen reserves
• Nervous tissue


  • No reserves of carbohydrates, lipids, or proteins, requires reliable supply of glucose
• Metabolic disorders may result from inadequate nutrition, biochemical problems, or starvation
• Insulin


  Key hormone in the fed state, promotes anabolism
• Insulin's cellular mechanism of action


  1. Insulin binds to tyrosine kinase receptor

  2. Receptor phosphorylates insulin-receptor substrates (IRS)

  3. Second messenger pathways alter protein synthesis and existing proteins

  4. Membrane transport is modified

  5. Cell metabolism is changed
• Insulin


  Lowers plasma glucose, increases glucose transport into cells, enhances utilization and storage of glucose, enhances utilization of amino acids, promotes fat synthesis
• Glucagon


  Key hormone in the fasted state, generally antagonist to insulin, prevents hypoglycemia
• Glucagon's role in the fasted state


  Stimulates glycogenolysis and gluconeogenesis in the liver
• Glucose transport in the fasted state

  No insulin to bind to receptor, glucose unable to enter cell
• Glucose transport in the fed state


  Insulin signals the cell to insert GLUT4 transporters into the membrane, allowing glucose to enter cell
• Glucose transport in the liver in the fasted state

  Hepatocyte makes glucose and transports it out into the blood, using GLUT2 transporters
• Glucose transport in the liver in the fed state


  Glucose concentration gradient reverses, glucose enters the hepatocyte
• Fasted-state metabolism road map


  Liver glycogen becomes glucose, adipose lipids become free fatty acids and glycerol, muscle glycogen and proteins can be used for energy, brain can use glucose and ketones for energy

  
• Tracellular [glucose] low


  Requires energy
• ATP


  Energy currency of the cell
• GLUT2


  Glucose transporter
• Insulin


  Hormone that regulates blood glucose levels
• Fed state


  1. Glucose concentration gradient reverses

  2. Glucose enters the hepatocyte
• Fasted state


  1. Hepatocyte makes glucose

  2. Transports it out into the blood, using GLUT2 transporters
• Hepatocyte


  • Stores glucose as glycogen
  • Releases glucose into blood
• Food intake


  Requires energy