HBG 17 ( Body Integration)

• Communication between tissues is mediated by:

  • Nervous system
  • Availability of circulating substrates
  • Variation in the levels of plasma hormones
• Integration of energy metabolism is controlled primarily by the hormones action such as:

  • Insulin
  • Glucagon
  • Catecholamines
• 4 major organs important in fuel metabolism are:

  • Liver
  • Adipose tissue
  • Muscle
  • Brain
• Important metabolic pathways include:

  • Glycolysis: glucose oxidation for ATP production
  • Citric acid cycle: acetyl CoA oxidation
  • Pentose phosphate pathway: synthesis of pentoses
  • Fatty acid beta-oxidation: breakdown of fatty acids into acetyl CoA for Kreb's cycle
  • Gluconeogenesis: glucose synthesis from smaller precursors for brain utilization
• Common intermediates in metabolic pathways are:

  • Acetyl-CoA
  • NADH and FADH2
  • NADPH
• Metabolic profile of organs:

  A. Metabolic Profile of Brain:

  • Neurons use glucose as the main energy source
  • Brain requires a steady supply of glucose
  • In starvation, ketone bodies replace glucose

  B. Metabolic Profile of Muscles:

  • Major fuels are glucose, fatty acids, and ketone bodies
  • Large storage of glycogen in muscles
  • Glucose is preferred fuel for activity, with lactate production
  • Fatty acids are major fuel in resting muscles and heart

  C. Metabolic Profile of Adipose Tissue:

  • Synthesizes and stores fatty acids as triacylglycerols
• • Glucagon activates hormone-sensitive lipase for triacylglycerol breakdown

  D. Metabolic Profile of the Liver:

  • Maintains steady glucose concentration in blood
  • Functions include gluconeogenesis, glycogen synthesis and degradation
  • Synthesizes ketone bodies from excess acetyl-CoA
• Hormonal control is mainly effected by:

  • Insulin and glucagon
  • Insulin facilitates glucose uptake, glycogen storage, reduces fat use as energy, promotes fatty acid synthesis, and fat accumulation in adipose tissue
• Biosynthesis of Insulin:

  • Synthesized as preproinsulin, converted to insulin
  • Stored in cytosol granules and released by insulinase enzyme
  • Plasma half-life of about 6 minutes
• Mechanism of Insulin Action:

  • Binds to specific receptors in cell membranes
  • Leads to various biological actions
  • Involves insulin receptor, signal transduction, and membrane effects
• Insulin secretion is stimulated by glucose uptake
• Fed-fast cycle states:

  • Fed or absorptive state (lasts 3 hours after a meal)
  • Post absorptive or early fasting state (from 3 hours to 12-18 hours after a meal)
  • Fasting state (from 18 hours to 2 days)
  • Starvation state or long-term fast (several weeks)
• Communication between tissues is mediated by:

  • Nervous system
  • Availability of circulating substrates
  • Variation in the levels of plasma hormones
• Integration of energy metabolism is controlled primarily by the hormones action such as:

  • Insulin
  • Glucagon
  • Catecholamines
• 4 major organs important in fuel metabolism are:

  • Liver
  • Adipose tissue
  • Muscle
  • Brain
• Important metabolic pathways include:

  • Glycolysis: glucose oxidation for ATP
  • Citric acid cycle: acetyl CoA oxidation
  • Pentose phosphate pathway: synthesis of pentoses
  • Fatty acid beta-oxidation: breakdown into acetyl CoA for Kreb's cycle
  • Gluconeogenesis: glucose synthesis from smaller precursors for brain
• Common intermediates in metabolic pathways are:

  • Acetyl-CoA
  • NADH and FADH2
  • NADPH
• • Maintains steady glucose concentration in blood
  • Functions include gluconeogenesis, glycogen synthesis/degradation
  • Synthesizes ketone bodies with excess acetyl-CoA
• Metabolic profile of organs:

  A. Metabolic Profile of Brain:

  • Neurons use only glucose as energy source
  • Brain needs steady glucose supply
  • In starvation, ketone bodies replace glucose

  B. Metabolic Profile of Muscles:

  • Major fuels: glucose, fatty acids, ketone bodies
  • Large glycogen storage
  • Glucose preferred for activity, lactate production
  • Fatty acids major fuel in resting muscles and heart

  C. Metabolic Profile of Adipose tissue:

  • Synthesizes and stores fatty acids as triacylglycerols
  • Glucagon activates hormone-sensitive lipase for breakdown

  D. Metabolic Profile of the Liver:
• Hormonal control is mainly effected by insulin and glucagon:

  • Insulin released when blood glucose levels are high
  • Insulin facilitates glucose uptake, glycogen storage, reduces fat use, promotes fatty acid synthesis
  • GLUTs are glucose transporters
  • Insulin secretion is stimulated by glucose uptake
• Biosynthesis of Insulin:

  • Preproinsulin converted to insulin
  • Insulin stored in cytosol granules
  • Released by insulinase enzyme
  • Insulin has a plasma half-life of about 6 mins
• Mechanism of Insulin Action:

  • Binds to specific receptors in cell membranes
  • Leads to various biological actions
  • Signal transduction involves IRSs
  • Insulin stimulates glucose transport and GLUT-4 recruitment
• Fed-fast cycle states:

  • Fed or absorptive state lasts 3 hours after a meal
  • Post absorptive or early fasting state from 3 to 12-18 hours after a meal
  • Fasting state from 18 hours to 2 days
  • Starvation state or long term fast can last several weeks