MSc Medical Biochemistry,
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
epinephrine, Glucagon Hormone sensitive lipase
Beta oxidation in Liver
High NADH TCA cycle
KETONE BODIES- SYNTHESIS
Ketone body synthesis is active in 1. starvation and
2.uncontrolled diabetes mellitus
ACETYL-COA + ACETYL-COA
Acetyl CoA HMG CoA synthase
Site of synthesis liver mitochondria
ACETO ACETIC ACID
ACETONE 3-HYDROXY BUTYRATE
HMG CoA Lyase
Fate and utilization
Utilization of Ketone bodies in
Muscle , Myocadium for ATP
Succinyl coA – Acetoacetate
CoA Transferase (Thiophorase)
Acetoacetate is major energy source in cardiac
muscle and renal cortex; also in brain in starvation
Ketones in Diabetes Mellitus
In presence of insulin:
• Enhanced glucose uptake by tissues
• Decreased mobilization of lipids by
In absence of insulin:
• Decreased glucose uptake by tissues
• Increased mobilization of lipids by
1.Lipolysis of TAG
3. Acetyl co-A
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.
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