Ketone Bodies.pptx

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 BODIE s 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 Acetoacetic acid CH3-CO-CH2-COOH β)3 (- hydroxybutyric acid CH3-CHOH-CH2-COOH 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 .

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

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

9. 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. .

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

11. 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.

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

13. 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 ).

14. 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.

15. 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).

16. 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.

17. 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 s tarvation and severe uncontrolled diabetes mellitus

18. 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

19. 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.

20. 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

21. Regulation of ketogenesis

22. 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.)

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

24. CAUSES OF KETOS IS

25. 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

26. CONSEQUENCES OF KETOSI s

27. DIAGNOSIS OF KETOSIS

28. 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.

29. Expected Questions Short Explain the ketone bodies.

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