biochemistry

• Triacylglycerol (TG)


  Lipid stored in adipose tissue
• Fat mobilisation from adipose tissue

  1. Esterification (Synthesis)

  2. Lipolysis (Degradation)

  
• Esterification


  The process of synthesizing triacylglycerol from glycerol and fatty acids
• More insulin


  Higher rate of esterification, higher accumulation of TG
• Factors affecting esterification


  • Supply of fatty acyl-CoA
  • Supply of glycerol 3-phosphate (indirectly, supply of glucose)

  
• Lipolysis


  The process of breaking down triacylglycerol into fatty acids and glycerol
• More glucagon


  Higher rate of lipolysis, lower/decrease in TG accumulation in adipocytes

  
• Factors affecting lipolysis


  • Activity of hormone sensitive lipase (HSL)

  
• Esterification in well-fed state

  1. Carbohydrate -> glucose -> taken to adipose tissue via GLUT4 -> glucose 6-phosphate -> glycerol 3-phosphate

  2. Chylomicron transport dietary TG (from intestine) -> adipose tissue

  3. VLDL transports TG (synthesized by liver) -> adipose tissue

  4. Lipoprotein lipase will breakdown TG inside chylomicron and VLDL

  5. Free fatty acids -> fatty acyl-CoA

  6. 3 fatty acyl-CoA & 1 glycerol 3-phosphate undergo esterification forming TG

  7. TG is stored in adipose tissue

  
• Lipolysis in starvation


  1. Hormone sensitive lipase (in adipose tissue) is activated and catalyzes the breakdown of stored TG -> fatty acid and glycerol

  2. Fatty acid will be utilized to produce energy by other tissues

  
• Insulin


  Stimulates translocation of GLUT-4 from cytosol to plasma membrane, activates lipoprotein lipase, reduces the release of fatty acid from adipose tissues, increases activity of key enzymes

  
• Lipolytic hormones (glucagon, adrenaline & adrenocorticotropic hormone)


  Activate hormone sensitive lipase by phosphorylation

  
• Ketone bodies


  Acetoacetate, acetone & β-hydroxybutyrate
• Ketogenesis by liver


  1. Liver is flooded with FA from adipose tissues

  2. Increased hepatic acetyl CoA

  3. Inhibition of pyruvate dehydrogenase

  4. Activation of pyruvate carboxylase

  5. OAA is used by liver for gluconeogenesis rather than TCA cycle

  6. Acetyl CoA is channeled into ketone bodies production

  
• Ketogenesis & utilization by peripheral tissues

  1. Early stage of fasting: heart & skeletal muscle use ketone bodies to conserve glucose for CNS & erythrocytes

  2. Prolonged starvation: high ketone bodies in blood ensures their efficient uptake by brain -> spare glucose consumption

  
• Ketone bodies are synthesized by liver during high rates of lipolysis (long-term starvation or uncontrolled diabetes)

  
• Properties of ketone bodies

  • Water soluble -> not needed to be incorporated in lipoproteins or carried by albumins
  • Used by brain, muscle, kidney & intestine
  • Not used by liver and RBC
  • Alternative fuel for cells
  • Decreased breakdown of protein -> reduced muscle wasting
  • Acetoacetate & β-hydroxybutyrate are metabolically useful, acetone is metabolically useless
• Ketosis


  Elevated levels of ketone bodies in blood
• Ketoacidosis


  Elevation of ketone bodies in blood resulting in acidaemia

  
• In diabetes mellitus type I, insulin levels are low/deficient, no glucose uptake from blood to cell, ketosis occurs, cell mobilizes free FAs from adipocytes, stimulation of lipolysis by liver/more FAs in liver, excess acetyl CoA, NAD+:NADH pool decrease, TCA cycle slows down, increased ketogenesis in liver

  
• In ketoacidosis, each ketone body loses a proton (H+) which becomes acidic and lowers the body pH, excretion of glucose and ketone bodies in urine can lead to dehydration, more H+ in a decreased volume of plasma can cause severe acidosis
• In diabetic ketoacidosis, glucose remains constant due to gluconeogenesis, free FAs remain constant due to continuation of lipolysis, ketone bodies increase markedly due to increased FA oxidation and ketogenesis