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KETONE BODIESKETONE BODIES
Tapeshwar YadavTapeshwar Yadav
))LecturerLecturer((
BMLT, DNHEBMLT, DNHE,,
M.Sc. Medical BiochemistryM.Sc. Medical Biochemistry
Ketone BodiesKetone Bodies
They are;
Acetoacetic acid CH3-CO-CH2-COOH
β)3(-hydroxybutyric acid CH3-CHOH-CH2-COOH
Acetone CH3-CO-CH3
KetogensesisKetogensesis
Definition:
It means Synthesis of ketone bodies.
Site.
Mitochondrial matrix of liver cells.
Steps of KetogensesisSteps of Ketogensesis
Properties of Ketone BodiesProperties of Ketone Bodies
1. They are water soluble substances.
2. They are synthesized at a relatively low rate in
well nourished individuals.
3. Plasma level of ketone bodies < 1mg/dl.
4. Urinary level of ketone bodies <3 mg/24 hour
urine.
5. 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.
6. Acetoacetate and β-hydroxybutyrate are relatively
strong acids.
KetolysisKetolysis
Definition
It is the utilization (oxidation) of ketone bodies.
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.
.
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 .
Steps of KetolysisSteps of Ketolysis
.
CH3 – CH – CH2 - COOH
OH
β - hydroxybutyrate
CH3 – C – CH2 - COOH
O
Acetoacetate
NAD+
NADH+H+
3ATPs
ETC
β - hydroxybutyrate
dehydrogenase
Steps of KetolysisSteps of Ketolysis
Thiophorase
Energetics of KetolysisEnergetics of Ketolysis
 Oxidation of one mole of 3-hydroxbutyrate
27 ATPs.
 Oxidation of one mole of acetoacetateate
24 ATPs
Relation between Ketogenesis and KetolysisRelation between Ketogenesis and Ketolysis
Ketoacidosis (Ketosis)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).
.
Causes of KetosisCauses of Ketosis
1. Prolonged starvation.
2. Severe dieting.
3. Uncontrolled diabetes mellitus.
Mechanism (Pathogenesis) of KetosisMechanism (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.
Prolonged
starvation
Severe
dieting
Uncontrolled
DM
Mechanism of KetosisMechanism of Ketosis
insulin Glucagon
Lipolysis
Plasma FFA
FA oxidation
Acetyl COA that can not enter CAC
due to defect in CHO metabolism
Ketogenesis
Ketosis
Consequences of Ketosis:-
 Metabolic acidosis.
 Smell of acetone.
 Osmotic diuresis.
 Loss of cations.
 Dehydration.
 Coma.
Diagnosis of Ketosis:-
 Rothera’s test.
 Estimation of serum electrolytes.
 Acid-base parameters.
 Glucose & Urea estimation.
Rothera’s test:-
 Saturate 5ml of urine with solid NH3SO4.
 Add a few drops of freshly prepared sodium
nitroprusside followed by 2ml of liquid ammonia
along the side of the test tube.
Result:-
Development of a purple ring indicates the
presence of ketone bodies in urine.
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.
THANK YOU

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Ketone bodies

  • 1. KETONE BODIESKETONE BODIES Tapeshwar YadavTapeshwar Yadav ))LecturerLecturer(( BMLT, DNHEBMLT, DNHE,, M.Sc. Medical BiochemistryM.Sc. Medical Biochemistry
  • 2. Ketone BodiesKetone Bodies They are; Acetoacetic acid CH3-CO-CH2-COOH β)3(-hydroxybutyric acid CH3-CHOH-CH2-COOH Acetone CH3-CO-CH3
  • 3. KetogensesisKetogensesis Definition: It means Synthesis of ketone bodies. Site. Mitochondrial matrix of liver cells.
  • 4. Steps of KetogensesisSteps of Ketogensesis
  • 5. Properties of Ketone BodiesProperties of Ketone Bodies 1. They are water soluble substances. 2. They are synthesized at a relatively low rate in well nourished individuals. 3. Plasma level of ketone bodies < 1mg/dl. 4. Urinary level of ketone bodies <3 mg/24 hour urine.
  • 6. 5. 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. 6. Acetoacetate and β-hydroxybutyrate are relatively strong acids.
  • 7. KetolysisKetolysis Definition It is the utilization (oxidation) of ketone bodies. 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. .
  • 8. 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 .
  • 9. Steps of KetolysisSteps of Ketolysis . CH3 – CH – CH2 - COOH OH β - hydroxybutyrate CH3 – C – CH2 - COOH O Acetoacetate NAD+ NADH+H+ 3ATPs ETC β - hydroxybutyrate dehydrogenase
  • 10. Steps of KetolysisSteps of Ketolysis Thiophorase
  • 11. Energetics of KetolysisEnergetics of Ketolysis  Oxidation of one mole of 3-hydroxbutyrate 27 ATPs.  Oxidation of one mole of acetoacetateate 24 ATPs
  • 12. Relation between Ketogenesis and KetolysisRelation between Ketogenesis and Ketolysis
  • 13. Ketoacidosis (Ketosis)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). .
  • 14. Causes of KetosisCauses of Ketosis 1. Prolonged starvation. 2. Severe dieting. 3. Uncontrolled diabetes mellitus.
  • 15. Mechanism (Pathogenesis) of KetosisMechanism (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.
  • 17. FA oxidation Acetyl COA that can not enter CAC due to defect in CHO metabolism Ketogenesis Ketosis
  • 18. Consequences of Ketosis:-  Metabolic acidosis.  Smell of acetone.  Osmotic diuresis.  Loss of cations.  Dehydration.  Coma.
  • 19. Diagnosis of Ketosis:-  Rothera’s test.  Estimation of serum electrolytes.  Acid-base parameters.  Glucose & Urea estimation.
  • 20. Rothera’s test:-  Saturate 5ml of urine with solid NH3SO4.  Add a few drops of freshly prepared sodium nitroprusside followed by 2ml of liquid ammonia along the side of the test tube. Result:- Development of a purple ring indicates the presence of ketone bodies in urine.
  • 21. 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.