M.

Prasad Naidu
MSc Medical Biochemistry,
Ph.D.Research Scholar
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
 Adipose tissue.
During Starvation
epinephrine, Glucagon Hormone sensitive lipase
Lipolysis

Fatty acid

Beta oxidation in Liver

Acetyl CoA
 TCA cycle
High NADH

Low NADH

Muscle ,
Myocardium Energy production
KETONE BODIES- SYNTHESIS
Ketone 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 CoA HMG CoA synthase

CoA
HMG CoA
 HMG-COA

CoA
HMG CoA Lyase

ACETO ACETIC ACID

NADH
Sponteneous Dehydrogenase
NAD+
ACETONE
CO2 3-HYDROXY BUTYRATE
3-HYDROXY BUTYRATE
 3

Fate and utilization

Succinyl coA Acetoacetate
Fig 10.18
CoA Transferase (Thiophorase)

Utilization of Ketone bodies in

Muscle , Myocadium for ATP
production
Acetoacetate is major energy source in cardiac
muscle and renal cortex; also in brain in starvation
and diabetes
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
 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
Regulation of Ketone body synthesis
Disorders
Fig 10.21

Ketonemia --- ketonuria -------- ketosis

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