The document discusses ketone bodies, which are formed in the liver from fatty acid breakdown and include acetoacetate, beta-hydroxybutyrate, and acetone. These water-soluble molecules provide an energy source for other tissues and are produced more during starvation or uncontrolled diabetes. Ketosis refers to high levels of ketone bodies in the blood and urine, while ketoacidosis is a dangerous condition where ketone levels become severely high, causing a metabolic acidosis. Treatment involves insulin administration and fluid/electrolyte management to prevent complications like dehydration.

1. METABOLISM OF KETONE
BODIES
Dr. Manmeet Kochar

2. Ketone bodies
• Acetone
• Acetoacetate
• Beta- hydroxybutyrate

3. Properties of ketone bodies
• Water soluble
• Produced during excessive breakdown of fatty acids
• Acetone is volatile – Expelled out through Lungs
• Acetoacetate and 3 Hydroxybutyrate are excreted through urine
• Plasma level < 1mg/dl
• Urinary level < 3mg/24hr

4. Interconversion of ketone bodies.

5.  Acetoacetate and β-hydroxybutyrate are interconverted by the
mitochondrial enzyme β-hydroxybutyrate dehydrogenase.
 Acetoacetate continually undergoes spontaneous nonenzymatic
decarboxylation to yield acetone
• Ketone bodies are water soluble and energy yielding substances.
• Acetone is an exception, since it cannot be metabolized and is readily
exhaled through lungs.

8. 1. Formation of Acetoacetyl CoA
2. Formation of HMG-CoA ( HMG CoA
synthase present only in liver)
3. Formation of Acetoacetate
4. Formation of Acetone
5. Formation of Beta-hydroxybutyrate

17. Ketone body oxidation
Ketone bodies, synthesized in
liver, are rich in metabolic
energy.
Brain also switches to using
predominantly acetoacetate in
starvation and diabetes.
 Erythrocytes ( lack of
mitochondria ) and liver
(thiophorase)cannot oxidize
ketone bodies.

22.  Ketone bodies are water soluble transportable form of derivatives of acetyl-CoA.
They do not need to be incorporated into lipoproteins or carried by albumins as do
the other lipids.

23. Ketosis & Ketoacidosis

24. Ketonemia & Ketonuria
• Blood level of ketone bodies increased – Ketonemia
• Excretion of ketone bodies in urine increased - Ketonuria

27. Ketosis ; Ketoacidosis
Ketonemia + Ketonuria = Ketosis
Ketone bodies (acetoacetic acid & 3-OH Butyric acid ) are
acidic in nature
Bicarbonate (HCO3-) level of the blood decreases –
metabolic acidosis
Metabolic acidosis is due to accumulation of ketone bodies
so it is called ketoacidosis
Hydrogen ions are neutralized by bicarbonate (HCO3 -) of the
blood

28. Ketoacidosis
seen when there is excess fatty acid oxidation by the liver
Excess fatty acid oxidation by the liver – when there is excess
mobilization of the fatty acids from adipose tissue
Excess mobilization of fat from adipose tissue when
(Insulin : Glucagon) ↓
1. Uncontrolled Diabetes Mellitus:
Diabetic ketoacidosis
2. Prolonged Starvation:
Starvation Ketoacidosis

29. Diabetic Ketoacidosis Starvation Ketoacidosis
Relative or absolute deficiency of insulin
combined with counter regulatory hormone
excess
(Insulin : Glucagon) ↓
Hyperglucagonemia alters hepatic metabolism to favour ketone body formation,
through activation of the enzyme carnitine palmitoyl transferase I.
Excess b-oxidation of fatty acids in the hepatocytes
Excess mobilization of fatty acids
Blood glucose level is decreased
Excess ketone body formation

30. Salient Features of Ketosis …..
• Acidosis
• Kussmaul's respiration
• Smell of acetone in patient's breath.
• Osmotic diuresis induced by ketonuria may lead to dehydration
• Sodium loss (The ketone bodies are excreted in urine as their sodium
salt)
• Dehydration
• Coma

32. Management of Ketoacidosis
 Treatment is to give insulin and glucose
 When glucose and insulin are given intravenously, potassium is trapped
within the cells.
 Fatal hypokalaemia can occur Clinician should always monitor the
electrolytes
Administration of bicarbonate, and maintenance of electrolyte and fluid
balance

33. SUMMARY
• The ketone bodies (acetoacetate, 3-hydroxybutyrate, and acetone) are
formed in hepatic mitochondria when there is a high rate of fatty acid
oxidation.
• The pathway of ketogenesis involves synthesis and breakdown of
HMG-CoA by two key enzymes, HMG CoA synthase, and HMG-CoA
lyase.
• Ketone bodies are important fuels in extrahepatic tissues.
• Ketosis is mild in starvation but severe in diabetes mellitus.

34. THANK YOU….