Ketone bodies are produced by the liver and used peripherally as an energy source when glucose is not readily available.

1. Ketone
Bodies
1

2. INTRODUCTION
• Ketone bodies are metabolic products that are produced in excess
during excessive breakdown of fatty acids.
• Acetoacetate, acetone and β- hydroxybutyrate are collectively
known as ketone bodies (acetone bodies).
• Only the first two are true ketones while β-hydroxybutyrate does
not possess a keto (C=O) group.
• Ketone bodies are water-soluble and energy yielding.
• In a normal man, concentration of ketone bodies in the blood is
usually less than 3 mg/100ml.

3. SIGNIFICANCE OF KETONE BODIEs
• Alternate source to glucose for energy needs
• Ketone bodies represent an alternative to glucose for the provision
of energy to the cells.
• Production of ketone bodies under conditions of cellular energy
deprivation.
• Ketone bodies are produced when excessive fatty acids are being
oxidized (because of increased adipose tissue lipolysis) and
glucose availability to the cells is limited.
• Such situations are seen in conditions such as diabetes mellitus and
starvation.

4. Cont…..
• Utilization of ketone bodies by the brain
• Brain normally utilizes glucose for energy needs.
• Although ketone bodies cannot completely replace glucose for
energy needs in the brain, brain gets adapted to oxidize ketone
bodies during prolonged fasting and starvation.

5. TYPES OF KETONE BODIES
1. Acetoacetic acid CH3-CO-CH2-COOH
2. β)3(-hydroxybutyric acid CH3-CHOH-CH2-COOH
3. Acetone CH3-CO-CH3
• Only the first two are true ketones while β hydroxybutyrate does
not possess a keto (C O) group.
• Ketone bodies are water-soluble and energy yielding. Acetone,
however, is an exception, since it cannot be metabolized.

6. PROPERTIES OF KETONE
• They are water soluble substances.
• They are synthesized at a relatively
low rate in well nourished individuals.
• Plasma level of ketone bodies <
1mg/dl.
• Urinary level of ketone bodies <3
mg/24 hour urine.
• Acetone is synthesized in smaller
amounts than other ketone bodies.
• It is a non-metabolized end
product.
• It is a volatile substance that is
excreted by the lungs in the
expired air.
• Acetoacetate and β-hydroxybutyrate
are relatively strong acids.

8. DEFINITION OF KETOGENSESIS
It means synthesis of ketone bodies.
Site- Mitochondrial matrix of liver cells.

10. Ketolysis
Definition- It is the utilization (oxidation) of ketone
bodies.

11. Cont….
Site –
• Mitochondrial matrix of extra hepatic tissues especially kidney
cortex, cardiac and skeletal muscles which normally use ketone
bodies as a source of energy in preference to glucose.
• The brain can utilize ketone bodies as a source of energy only
during prolonged starvation and they provide about 75 % of its
energy needs. .

12. KETOLYSIS DOES NOT OCCUR IN
a. RBCs : due to absence of mitochondria
b. Liver : due to absence of thiophorase enzyme that is
required for the activation of ketone bodies .

13. Cont….
• During prolonged starvation, ketone bodies are the major fuel source
for the brain and other parts of central nervous system.
• It should be noted that the ability of the brain to utilize fatty acids
for energy is very limited.
• The ketone bodies can meet 50-70% of the brain’s energy needs.
• This is an adaptation for the survival of the organism during the
periods of food deprivation.

16. Energetics of Ketolysis
• Oxidation of one mole of Beta -hydroxbutyrate- 27
ATPs.
• Oxidation of one mole of acetoacetateate - 24 ATPs

17. Reactions of ketone bodies
• Beta -Hydroxybutyrate is first converted to
acetoacetate (reversal of synthesis) and metabolized.
• Acetoacetate is activated to acetoacetyl CoA by a
mitochondrial enzyme thiophorase (succinyl CoA
acetoacetate CoA transferase).

18. Reactions of ketone bodies
• The coenzyme A is donated by succinyl CoA, an
intermediate in citric acid cycle.
• Thiophorase is absent in liver, hence ketone bodies are
not utilized by the liver.
• Thiolase cleaves acetoacetyl CoA to two moles of acetyl
CoA.

19. Overproduction of ketone bodies
• In normal individuals, there is a constant production of
ketone bodies by liver and their utilization by
extrahepatic tissues.
• The concentration of ketone bodies in blood is
maintained around 1 mg/dl.
• Their excretion in urine is very low and undetectable by
routine tests (Rothera’s test).

20. Cont…..
• When the rate of synthesis of ketone bodies exceeds the rate of
utilization, their concentration in blood increases, this is known as
ketonemia.
• Ketonemia is predominantly due to incresed production of ketone
bodies rather than the deficiency in their utilization.
• The term ketonuria represents the excretion of ketone bodies in
urine.

21. Cont….
• The overall picture of ketonemia and ketonuria is commonly
referred to as ketosis.
• Smell of acetone in breath is a common feature in ketosis.
• Ketosis is most commonly associated with starvation and
severe uncontrolled diabetes mellitus

22. STARVATION
• Starvation : Starvation is accompanied by increased degradation of
fatty acids (from the fuel reserve triacylglycerol) to meet the energy
needs of the body.
• This causes an over production of acetyl CoA which cannot be fully
handled by citric acid cycle.
• Furthermore, TCA cycle is impaired due to deficiency of oxaloacetate,
since most of it is diverted for glucose synthesis to meet the essential
requirements (often unsuccessful) for tissues like brain.
• The result is an accumulation of acetyl CoA and its diversion for
overproduction of ketone bodies

23. KETONURIA AND WEIGHT LOSS
• Ketonuria and weight loss : The appearance of ketone bodies in
urine is an indication of active fat metabolism.
• Some programs designed for body weight loss encourage reduction
in carbohydrate and total calorie intake until ketone bodies appear in
urine.

24. Diabetes mellitus
• Diabetes mellitus is associated with insulin deficiency.
• This results in impaired carbohydrate metabolism and increased
lipolysis, both of them ultimately leading to the accumulation of
acetyl CoA and its conversion to ketone bodies.
• In severe diabetes, the ketone body concentration in blood
plasma may reach 100 mg/dl and the urinary excretion
may be as high as 500 mg/day

25. Regulation of ketogenesis
The ketone body formation
(particularly overproduction)
occurs primarily due to
nonavailability of
carbohydrates to the tissues.
This is an outcome of
excessive utilization of
fatty acids to meet the
energy requirements of
the cells.
The hormone glucagon
stimulates ketogenesis
whereas insulin inhibits.
The increased ratio of
glucagon/insulin in
diabetes mellitus
promotes ketone body
formation.
This is due to disturbances
caused in carbohydrate
and lipid metabolisms in
diabetes.

26. Ketogenic and antiketogenic substances
• The ketogenic substances (promote ketogenesis) include fatty
acids and certain amino acids (leucine, lysine, tyrosine etc.).
• The antiketogenic substances (inhibit ketogenesis) are
glucose, glycerol and glucogenic amino acids (e.g. glycine,
alanine, serine, glutamate etc.)

27. Ketoacidosis (Ketosis)
Definition- It is a metabolic disorder characterized by a triad of :
1. Ketonemia (increase ketone bodies in blood).
2. ketonuria (increase ketone bodies in urine).
3. acetone (fruity) odor of breath.
There are also dehydration, acidosis, coma, and death (if
untreated). .

28. CAUSES OF KETOSIS
Prolonged
starvation.
Severe dieting.
Uncontrolled
diabetes mellitus.

29. Mechanism (Pathogenesis) of Ketosis
• In all types of ketosis, there is a decrease in insulin/glucagon ratio, so
there is a defect in carbo- hydrate metabolism, so the body depends
on oxidation of fat as the main source of energy.
• so, there is excessive lipolysis in adipose tissue that yields large
amounts of glycerol and fatty acids.
• The latter are oxidized to produce large amounts of acetyl COA that
can not enter the citric acid cycle due to deficiency of oxalo-
acetate.
• Consequently, acetyl COA is diverted to the pathway of keto-genesis
leading to excessive formation of ketone bodies i.e. ketosis

32. CONSEQUENCES OF KETOSIs
Metabolic
acidosis.
Smell of
acetone.
Osmotic
diuresis.
Dehydration.
Coma.

33. DIAGNOSIS OF KETOSIS
Rothera’s test.
Estimation
of serum
electrolytes.
Acid-base parameters.
Glucose &
Urea
estimation.

34. Management of keto-acidosis
• Treatment is to give insulin & glucose. When glucose & insulin
are given intravenously, potassium is trapped within the cells.
• Administration of bicarbonate, and maintenance of electrolyte
and fluid balance are very important aspects.

35. Expected Questions
Short
• Explain the ketone bodies.

36. THANK YOU