Ketone bodies

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Ketone bodies

  1. 1. M.Prasad Naidu MSc Medical Biochemistry, Ph.D.Research Scholar
  2. 2. Ketone bodies  Normally, total body needs of energy (ATP) is met by various fuels . 1. Carbohydrates (glucose) 70%. 2. Fat (fatty acids) 25%. 3. Proteins (Amino acids) 5%. 4. Ketone bodies normally negligible %. In a normal well fed person ketone body concentration is only < 1mg/dl. In prolonged starvation its concentration may increase up to 500mg/dl
  3. 3. Adipose tissue. During Starvation epinephrine, Glucagon Hormone sensitive lipase Lipolysis Fatty acid Beta oxidation in Liver Acetyl CoA
  4. 4. Low NADH High NADH TCA cycle Energy production Muscle , Myocardium
  5. 5. KETONE BODIES- SYNTHESIS Ketone body synthesis is active in 1. starvation and 2.uncontrolled diabetes mellitus ACETYL-COA + ACETYL-COA Thiolase ACETO-ACETYL-COA Acetyl CoA HMG CoA synthase CoA HMG CoA Site of synthesis liver mitochondria
  6. 6. HMG-COA CoA ACETO ACETIC ACID Dehydrogenase ACETONE 3-HYDROXY BUTYRATE HMG CoA Lyase CO2 NADH NAD+ 3-HYDROXY BUTYRATE Sponteneous
  7. 7. Fate and utilization  Fig 10.18 3 Utilization of Ketone bodies in Muscle , Myocadium for ATP production Succinyl coA – Acetoacetate CoA Transferase (Thiophorase)
  8. 8. Acetoacetate is major energy source in cardiac muscle and renal cortex; also in brain in starvation and diabetes
  9. 9. Ketones in Diabetes Mellitus 10 In presence of insulin: • Enhanced glucose uptake by tissues • Decreased mobilization of lipids by adipocytes In absence of insulin: • Decreased glucose uptake by tissues • Increased mobilization of lipids by adipocytes
  10. 10. Regulation 1.Lipolysis of TAG 2. CAT-I 3. Acetyl co-A
  11. 11.  Ketosis does not occur in vivo unless there is an increase in the level of circulating free fatty acids that arise from lipolysis of triacylglycerol in adipose tissue.  Free fatty acids are the precursors of ketone bodies in the liver.
  12. 12.  The liver, both in fed and in fasting conditions, extracts about 30% of the free fatty acids passing through it, so that at high concentrations the flux passing into the liver is substantial.  Therefore, the factors regulating mobilization of free fatty acids from adipose tissue are important in controlling ketogenesis
  13. 13. Regulation of Ketone body synthesis
  14. 14. Disorders  Fig 10.21 Ketonemia --- ketonuria -------- ketosis
  15. 15. THANK YOU

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