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1. 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 .
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. Adipose tissue.
During Starvation
epinephrine, Glucagon Hormone sensitive lipase
Lipolysis
Fatty acid
Beta oxidation in Liver
Acetyl CoA

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

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

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

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

10. 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

11. Regulation
1.Lipolysis of TAG
2. CAT-I
3. Acetyl co-A

12.  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.

13.  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

15. Regulation of Ketone body synthesis

16. Disorders
 Fig 10.21
Ketonemia --- ketonuria -------- ketosis

17. THANK YOU