Metabolic Control in Tissues

Tissues that Regulate Overall Body Metabolism

• Liver, muscle, brain, and adipose tissues are the vital tissues that regulate overall body metabolism.

Metabolism in Skeletal Muscles

• Skeletal muscles make up about half of the body's solid mass and dominate energy metabolism.
• Muscles can use a wide variety of fuels, including glucose, fatty acids, and ketone bodies.
• Muscle energy demand varies with activity, with resting muscles depending mainly on fatty acid oxidation.
• Glucose derived from muscle glycogenolysis is primarily used by muscles only (no G-6-Phosphatase).
• Characteristics of energy metabolism in skeletal muscles:
  • Store about 250 grams of glycogen in the average adult man.
  • Lactate produced by exercising muscles diffuses to blood and is converted back into glucose in the Cori cycle.
  • Prolonged fasting and starvation cause increased rate of degradation of skeletal muscle proteins to provide carbon skeleton for gluconeogenesis.
  • Increased amino acid degradation results in the glucose-alanine cycle.
  • Creatine phosphate is necessary for maintaining ATP levels during exercise.

Differences between Sprinters and Marathon Runners

• Sprinters have large muscle mass, mainly consisting of white muscle fibers with high anaerobic capacity, and store considerable amounts of glycogen and creatine phosphate.
• Marathon runners have muscles consisting mainly of highly aerobic red muscles, densely packed with mitochondria and myoglobin.
• During the first seconds of a 100-meter sprint, ATP is rapidly reformed at the expense of phosphocreatine, catalyzed by creatine kinase.
• In marathon running, ATP synthesis is mainly powered by aerobic oxidation involving an increased rate of fatty acid mobilization and acetyl-CoA oxidation.

Metabolism in the Heart

• Heart muscles have a regular rhythm of contraction and relaxation.
• Heart has completely aerobic metabolism at all times.
• Mitochondria are more abundant in heart muscles than in skeletal muscles.
• Heart uses blood glucose, ketone bodies, and fatty acids, which are oxidized aerobically.
• There is also phosphocreatine in the heart.
• When blood vessels are blocked, the supplied tissue of the heart dies, leading to myocardial infarction or heart attack.

Metabolism in the Brain

• The brain of adult mammals normally uses only glucose as fuel.
• It has very active aerobic metabolism.
• It uses oxygen up to 20% of total consumption at rest.
• It does not store glycogen but depends on fresh glucose from the blood.
• When blood glucose falls below 2 mm (hypoglycemia), serious irreversible brain damage may occur.
• The brain does not use fatty acids from the blood but can use ketone bodies in prolonged fasting or starvation, which reserves muscle proteins from degradation.

Metabolism in Blood Cells

• Mammalian erythrocytes contain no mitochondria, thus are exclusively dependent on anaerobic glycolysis.
• They produce lactate, which diffuses to plasma, and can be used as a precursor for gluconeogenesis.
• RBCs use ATP for maintaining electrolyte balance via the action of Na+/K+ ATPase.

Metabolism in Adipose Tissues

• Adipocytes are the main fuel-storing tissues in the body, storing triacylglycerols that can support energy generation for several weeks.
• Because adipocytes lack the enzyme glycerol kinase, they use glucose for the provision of dihydroxyacetone phosphate required for the formation of glycerol-3-phosphate.
• Body response to starvation:
  • The total body reserve of fuel is sufficient to support energy demand for several weeks.
  • The average man possesses about 12% of his body weight as triacylglycerols, while females may store up to 25% of their body weight as fat.
  • The amount of carbohydrates stored is only about 2% of the fuel reserve.
  • The liver glycogen will be exhausted just a few hours after a meal.
  • The human body adapts metabolically during starvation by increasing the use of fuels other than carbohydrates.

Liver Metabolism

• The liver is a central organ in metabolism, containing all enzymes of major metabolic pathways.
• Unique pathways in the liver include:
  • Control of blood glucose levels.
  • Regulation of circulating fatty acids, amino acids, and other metabolites.
  • Steroid synthesis, bile acids, and vit-D activation.
  • Synthesis of most plasma proteins.
  • Disposal of toxic metabolites such as ammonia and bilirubin.
  • Inactivation and excretion of hormones and drugs.
  • Synthesis and export of essential nutrients and precursors.

Fate of Different Substances in the Liver

• In a well-fed state, glucose is taken up by hepatocytes and phosphorylated to G-6-P in a reaction catalyzed by glucokinase.
• Fates of glucose-6-P:
  • Glycogenesis.
  • G-6-P may be oxidized via glycolysis.
  • Pyruvate is the end product of aerobic glycolysis.
  • About 15% of G-6-P may be oxidized via the hexose monophosphate shunt.
  • Pyruvate may be converted into acetyl-CoA by PDHC.
  • Very little of acetyl-CoA derived from glycolysis in the liver is oxidized in the citric acid cycle for energy generation.

Fate of Absorbed Amino Acids and Lipids in the Liver

• Amino acids arriving at the liver in the fed state condition will primarily be used for protein synthesis.
• The liver is constantly turning over its protein to adjust its metabolic activities.
• In the fed state condition, the liver may actively use acetyl-CoA for synthesis of TAG and it also synthesizes phospholipids and cholesterol.

Fuel Metabolism in the Liver during Fasting

• 2-3 hours after the last meal, the levels of blood glucose start to decline, and insulin secretion decreases with a concomitant increase in glucagon release.
• This hormonal change will switch on and off the major metabolic pathways in the liver to conserve blood glucose concentration and promote the use of stored fuels.
• The glucagon stimulation of its receptor on hepatocytes will promote glucose release into blood by activating the enzymes of glycogenolysis and gluconeogenesis.
• The fatty acids oxidation becomes the principle source of energy in hepatocytes during fasting to synthesize ketone bodies (the acetoacetate and β-hydroxybutyrate).