Ketone bodies and metabolism-biochemistry

This slide consists of all the topics of ketone . This can be used for exam purpose for writing about Diabetic keto acidosis etc . Thank you

1. KETONe body metabolism BY:D hayanithi,dharani nivega,fazil,ezhil & dinesh

2. contents Introduction to ketone bodies K etogenesis and steps R egulation of ketogenesis K etolysis K etosis C auses of ketosis S alient features of ketosis D iagnosis and differential diagnosis

3. K etone bodies?? types Ketone bodies are water soluble organic compounds generated in human body under metabolic conditions. T hey are specially synthesised in the liver. T hey are secondary fuel for the body F ormed during excessive breakdown of fatty acids. W ater soluble and energy yeilding. TYPES: 1)Acetoacetate 2)beta-hydroxybutyric acid 3) acetone

4. U tilization K etone bodies are utilized by the body as an alternative energy source. B lood glucose prolonged starvation uncontrolled diabetes mellitus 1 L ow-carb diets & intense exercise ketone supplies energy for the brain,heart,muscles in conditions of decreased glucose levels. T hey serve as fuel for the brain,heart and muscles when the glucose levels are decreased.

5. Amount of Macronutrients in the body Usually,the body needs energy(ATP) which are classified into various fuels. Carbohydrates(glucose) – 70% F ats|(fatty acids) – 25% P rotiens (amino acids) – 5% normal well fed person ketone conc. – only<1mg/dl prolonged starvation ketone conc.- 500mg/dl

6. S ub-cellular site T his process begins in the mitochondria of liver after transport of fatty acyl CoA molecule into inner mitochondrial by carnitine shuttle.

7. ketogenesis Acetoacetate is the primary ketone body while Beta-hydroxybutyrate & acetone are secondary ketone bodies. E xclusively synthesised in liver mitochondria.

8. S teps of ketogenesis Condensation HMG-CoA production L ysis R eduction S pontaneous decarboxylation

9. R egulation of ketogenesis D uring starvation and DM, the blood level glucagon . I t inhibits glycolysis ,activates gluconeogenesis,lipolysis, malonyl CoA & stimulates ketogenesis. I nsulin is opp. LEVELS: - L1 : Lipolysis. - L2: entry of fatty acids to mitochondria. - L3: oxidation of Acetyl CoA.

10. KETOLYSIS Ketone bodies are utilized by the extrahepatic tissues. Heart muscle & renal cortex prefer ketone bodies to glucose. Skeletal muscle and brain utilize ketone as alternate form (as aldready said in the previous slides) REACTION:

11. ketosis I t is the process that happens when the body doesn’t have enough carbs to burn. When the rate of synthesis exceeds the ability of extrahepatic tissues to utilize them. T here will accumulation ketone in blood, which leads to ketonemia.

12. C auses for ketosis Diabetes mellitus: - uncontrolled diabetes is the most common cause for ketosis - even though glucose is plenty the deficiency of insulin causes accelerated lipolysis& more fatty acids are released into circulation. S tarvation : - in starvation the glucose supply is decreased .available oxaloacetate is sent to gluconeogenesis. - the high glucagon level favours ketogenesis. - on prolonged starvation brain derives 60 – 70% of energy from ketone bodies.

13. Salient features of ketosis M etabolic acidosis R educed buffers K ussamaul’s respiration S mell of acetone O smotic diuressis S odium loss D ehydration C oma

14. D iagnosis of ketosis T he presence of ketosis can be established by detection of ketone bodies in urine by Rothera’s test . ROTHERA’S TEST : saturate 5ml urine with solid ammonium sulfate. Add 3 drops of freshly prepared sodium nitroprusside by 2 ml of liqour ammoniaalong the sides of the test tube. This test indicates the presence of acetone in urine. T his test cannot detect Beta-hydroxy butyrate.

15. D iagnosis contd… G erhardt’s test: to 5 ml of urine add dil.ferric chloride soln. drop by drop, till it attains maximum precipitation of ferric phosphate which is obtained. I t eliminates phosphates which obscure the color in test. F ilter: filtrate,add excess ferric chloride . A red color indicates the presence of acetoacetic acid. T his is not a sensiotive test. S alicylates will give a false positive test.

16. D ifferential diagnosis T he urine of aas patient with diabetic ketoacidosis will give positive benedict’s test as well as rothera’s test. I n starvation ketosis,benedicts test is negative but rothera’s test will be positive. MANAGEMENT OPF KETOACIDOSIS: Treatment is to give insulin and glucose. W hen glucose and insulin are given through IV,the pottasium is trapped within the cells and fatal hypokalemia can occur. H ence, the electrolytes should be monitored everytime for the maintainence |& fluid balance are very important.