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Ketone Bodies.pptx
Ketone bodies are water-soluble metabolic products resulting from the excessive breakdown of fatty acids, primarily produced under conditions of energy deprivation such as starvation and diabetes. They serve as an alternative energy source, particularly for the brain, when glucose availability is limited. Ketosis, characterized by elevated levels of ketone bodies in blood and urine, can lead to metabolic acidosis and requires careful management, particularly in diabetic patients.
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Ketone Bodies.pptx
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- 2. INTRODUCTION • Ketone bodiesare 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 KETONEBODIEs • 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 ofketone 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 KETONEBODIES 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 Itmeans synthesis of ketone bodies. Site- Mitochondrial matrix of liver cells.
- 10. Ketolysis Definition- It isthe utilization (oxidation) of ketone bodies.
- 11. Cont…. Site – • Mitochondrialmatrix 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 NOTOCCUR 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 prolongedstarvation, 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 ketonebodies • 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 ketonebodies • 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 ketonebodies • 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 therate 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 overallpicture 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 WEIGHTLOSS • 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 • Diabetesmellitus 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 Theketone 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 antiketogenicsubstances • 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- Itis 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. Severedieting. Uncontrolled diabetes mellitus.
- 29. Mechanism (Pathogenesis) ofKetosis • 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. Smellof acetone. Osmotic diuresis. Dehydration. Coma.
- 33. DIAGNOSIS OF KETOSIS Rothera’stest. 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 • Explainthe ketone bodies.
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