Lipid Metabolism

Metabolism of Lipids following the syllabus of Medical Biochemistry of MBBS course

1. Dr. Farhana Atia Associate Professor Department of Biochemistry Nilphamari Medical College, Nilphamari Metabolism of lipids

2. Lipid metabolism

3. Triacylglycerol Fatty acids Acetyl CoA TCA Lipolysis -oxidation Esterification Lipogenesis CO2 Diet Cholesterol Ketone bodies Steroids Carbohydrate Amino acid Overview of lipid metabolism

4. Metabolism of Lipids

5. Fatty acid Metabolism Fatty acids are stored as Triacylglycerol Constitute 84% of stored energy Fatty acids mobilized from Triacylglycerol are oxidized to meet the energy needs of a cell

6. Utilization of fatty acids as a fuel 3 stages

7. Mobilization of FA from TG into tissues

8. β - Oxidation - definition

9. β - Oxidation - steps

10. Fatty Acid Oxidation Fatty acids are oxidized by most of the tissues in the body Brain, erythrocytes & adrenal medulla cannot utilize fatty acids for energy requirement.

11. Activation of fatty acids In cytoplasm. Activated to acyl CoA by thiokinase (acyl CoA synthetase). Two steps reaction & requires ATP , coenzyme A and Mg 2+ Two high energy phosphates are utilized, since ATP is converted to pyrophosphate ( PPi ). The immediate elimination of PPi makes this reaction totally irreversible.

12. Activation of fatty acids Fatty Acid Acyl-CoA Occurs in outer mitochondrial membrane for long chain fatty acids

13. Transport of Acyl CoA into Mitochondria The inner mitochondrial membrane is impermeable to FA A specialized carnitine carrier system ( carnitine shuttle ) operates to transport activated FA from cytosol to the mitochondria. Carnitine is β -hydroxy γ -trimethyl aminobutyrate, widely distributed (abundant in muscle).

14. Transport of Acyl CoA into Mitochondria Four stages. 1- Acyl group of acyl CoA is transferred to carnitine catalyzed by carnitine acyltransferase-I (CAT-I) (present on the outer surface of inner mitochondrial membrane)

15. Transport of Acyl CoA into Mitochondria Four stages. 2- The acyl-carnitine is transported across the membrane to mitochondrial matrix by a specific carrier protein (Translocase).

16. Transport of Acyl CoA into Mitochondria 3- Carnitine acyltransferase ll (CAT-II) (found on the inner surface of inner mitochondrial membrane) converts acyl-carnitine to acyl CoA.

17. Transport of Acyl-CoA into Mitochondria 4- The carnitine released returns to cytosol for reuse by translocase.

18. Sequence of Reactions of β -oxidation

19. β -Oxidation proper 1. Oxidation: Acyl CoA undergoes dehydrogenation by an FAD-dependent flavoenzyme, acyl-CoA dehydrogenase. A double bond is formed between α & β carbons (i.e., 2 & 3 carbons) oxidation

20. β -Oxidation proper 2. Hydration: Enoyl-CoA hydratase brings about the hydration of the double bond to form β - hydroxyacyl CoA. hydration

21. β -Oxidation proper 3. Oxidation β - Hydroxyacyl - CoA dehydrogenase catalyzes the second oxidation & generates NADH. The product is β -ketoacyl CoA oxidation

22. β -Oxidation proper 4. Cleavage: Final reaction Liberation of a 2 carbon fragment, acetyl CoA from acyl CoA. This occurs by a thiolytic cleavage catalyzed by β -ketoacyl CoA transferase ( thiolase ) Thiolysis

23. β -Oxidation proper The new acyl-CoA, containing two carbons less than the original, reenters the β -oxidation cycle. The process continues till the fatty acid is completely oxidized Harper’s Illustrated Biochemistry 31 st edition P-209

24. oxidation oxidation hydration thiolysis C 16 7 rounds Oxidation of palmitate In respiratory chain, transport of electron from FADH 2 & NADH leads to synthesis of 4 ATP Palmitate, C16 fatty acid undergoes 7 cycles of β -oxidation to yield 8 acetyl CoA. Acetyl CoA can enter citric acid cycle & get completely oxidized to CO 2 & H 2 O

25. Energy yield from β -Oxidation of palmitate (16C) Mechanism ATP yield I. β - 0xidation 7 cycles 7 FADH2 7 NADH (Oxidized by ETC Liberate 4 ATP) 7 X 4=28 II. From 8 Acetyl CoA Oxidized by citric acid cycle, each acetyl CoA provides 10 ATP 8 X 10=80 Total energy from one molecule of palmitate Energy utilized for activation (Formation of palmitoyl Co A) 108 -2 Net yield of ATP =106

26. Oxidation of odd chain fatty acids Oxidation of odd chain fatty acids is similar to that of even chain fatty acids At the end 3 carbon unit, propionyl CoA is produced. Propionyl CoA is converted into succinyl CoA Propionyl CoA  Methyl malonyl CoA succinyl CoA Succinyl CoA enters the TCA cycle , & converted into oxaloacetate, it is used for gluconeogenesis

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