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KETONE BODIES

BIOCHEMISTRY

mprasadnaidu
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KETONE BODIES

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  1. Ketone bodies M.Prasad Naidu MSc Medical Biochemistry, Ph.D.Research Scholar

  2. Ketone bodies • Normally, total body needs of energy (ATP) is met by various fuels . • Carbohydrates (glucose) 70%. • Fat (fatty acids) 25%. • Proteins (Amino acids) 5%. • 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. Adipose tissue. During Starvation epinephrine, Glucagon Hormone sensitive lipase Lipolysis Fatty acid Beta oxidation in Liver Acetyl CoA

  4. TCA cycle High NADH Low NADH Muscle , Myocardium Energy production

  5. KETONE BODIES- SYNTHESISKetone body synthesis is active in 1. starvation and 2.uncontrolled diabetes mellitus Site of synthesis liver mitochondria ACETYL-COA + ACETYL-COA Thiolase ACETO-ACETYL-COA Acetyl CoAHMG CoA synthase CoA HMG CoA

  6. HMG CoA Lyase HMG-COA CoA ACETO ACETIC ACID Dehydrogenase ACETONE 3-HYDROXY BUTYRATE NADH Sponteneous NAD+ CO2 3-HYDROXY BUTYRATE

  7. Fate and utilization 3 Succinyl coA – Acetoacetate CoA Transferase (Thiophorase) • Fig 10.18 Utilization of Ketone bodies in Muscle , Myocadium for ATP production

  8. Acetoacetate is major energy source in cardiac muscle and renal cortex; also in brain in starvation and diabetes

  9. Ketones in Diabetes Mellitus • 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. Regulation 1.Lipolysis of TAG 2. CAT-I 3. Acetyl co-A

  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. 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. Regulation of Ketone body synthesis

  14. Disorders • Fig 10.21 Ketonemia --- ketonuria -------- ketosis

  15. THANK YOU

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