1. LECTURE 10 Introduction to lipid metabolism and oxidation of fatty acids I
V. SRIDEVI

2. OBJECTIVES Brief overview of the metabolism of lipids
Transport of fatty acids into mitochondria
ß Oxidation of fatty acids and energetics of ß oxidation of fatty acids.

3. Brief overview of the metabolism of lipids
The major aspects of lipid metabolism are
Fatty Acid Oxidation to produce energy and
Synthesis of lipids (lipogenesis)
Lipid metabolism is closely connected with carbohydrate metabolism which may be converted to fat.

4. Brief overview of the metabolism of lipids…
Enzymic degradation of dietary lipids by pancreatic enzymes in the small intestine to produce glycerol and fatty acids.

5. Triacylglycerol degradation: Triacylglycerol molecules are acted upon by an esterase, pancreatic lipase, which preferentially removes the fatty acids at carbons 1 and 3. The primary products of hydrolysis are a mixture of monoacylglycerol and free fatty acids

6. Dietary lipids (Triacylglycerol)
Monoacylglycerol
Fatty acids

7. Fate of free fatty acids:
Free fatty acids can be taken up by adipocytes.
Adipocytes can re-esterify free fatty acids to produce triacylglycerol molecules, which are stored until the fatty acids are needed by the body.
Alternatively, the free fatty acids are taken up by cells. Most cells can oxidize fatty acids to produce energy.

8. Fate of glycerol:
Glycerol or monoacylglycerol which is released from triacylglycerol is used almost exclusively by the liver
Glycerol is used to produce glycerol 3-phosphate
Glycerol 3-phosphate is converted to dihydroxyacetone phosphate which can enter glycolysis or gluconeogenesis.

9. Fate of Glycerol

10. Oxidation of fatty acid
1. Hydrolysis of triacylglycerol by lipase (lipolysis)
Occurs in the cell cytosol of adipose cells. The hydrolysis of triacylglycerol produces glycerol and free fatty acids.
The FFA travel in the blood bound to albumin and are taken up by muscle or liver cells for oxidation.
2. Activation of fatty acids
Before they can be oxidized, fatty acids are activated by attachment
to CoA to form acyl CoA molecules; this takes place in the cell
cytosol.
3. Transport into mitochondria
β-oxidation occurs in the mitochondrial matrix. The acyl CoA
molecules are transported into the mitochondria by the carnitine shuttle.
4. β-oxidation
Fatty acids are degraded by a cyclical sequence of four reactions oxidation, hydration, oxidation, thiolysis.

11. Fatty Acid Breakdown
The major pathway for the catabolism of fatty acids is a mitochondrial pathway called β-Oxidation.
Occurs in mitochondrial matrix.
Fatty acids are converted to their acyl coenzyme A (CoA) derivatives and then degraded by successive removal of acetyl CoA (two-carbon) units from the end of the fatty acid.
Saturated fatty acids of even numbered carbon chains.
Pathway produces
Reoxidation of FADH2
Reoxidation of NADH.
Oxidation of acetyl coA in the TCA cycle

12. I . Activation of fatty acids. Fatty acid
CoA ATP(2)
Thiokinase
(Acyl coA synthase)
AMP + PPi
Acyl CoA
II. Transport of fatty acids into mitochondria.
Cytosol Inner Mitochondrial
mitochondrial matrix
Acyl CoA Carnitine Carnitine Acyl CoA
carnitine Carrier carnitine
acyl transferase I protein acyl transferase II
CoA Acyl carnitine Acyl carnitine
CoA
Carnitine acyl carnitine translocase

13. Carnitine shuttle

14. Carnitine shuttle
Carnitine acyl transferase I(CAT- I) otherwise called as Carnitine palmitoyl transferase I(CPT-I)
Carnitine acyl transferase II(CAT- II) otherwise called as Carnitine palmitoyl tranferase II(CPT-II).
Carnitine can be obtained from diet -primarily from meat products. Also can be synthesized from amino acid lysine and methionine by an enzymatic pathway found in liver and kidney but not in skeletal and heart muscle.

16. Reaction Sequence in -Oxidation

17. Beta Oxidation
Acyl coA dehydrogenase
Acyl coA dehydrogenase

18. Beta Oxidation
Enoyl coA hydratase

19. Hydroxy acyl coA dehydrogenase
Beta Oxidation
Hydroxy acyl coA dehydrogenase

20. Beta Oxidation
Keto acyl coA thiolase

21. Energetics of palmitic acid oxidation: calculate the ATP production when (16 carbon) is completely oxidized.
Mechanism ATP yield
1. -oxidation 7 cycles I step liberates 2 ATP(2x7)
III step gives 3 ATP(3x7)
2. From 8 acetyl CoA Oxidized by citric acid cycle, each acetyl CoA
provides 12 ATP
Total energy from one molecule of palmitate Energy utilized for activation in the I step
Net yield of oxidation of one molecule of palmitate
Palmitic acid C16H32O2
                                 

22. Beta Oxidation

23. Beta Oxidation

24. Beta Oxidation

25. Lipid Metabolism

26. Use the criteria for understanding and describing all pathways
Names:
Functions:
Substrates:
Product:
Control Enzymes:
Regulation:
Compartment(s):
Tissues of interest:

27. Learning Outcomes By the end of lecture, students should be able to:
Explain the role of carnitine in the transport of fatty acids into the mitochondrion for oxidation.
Describe how fatty acids can be used as fuels via oxidative conversion (especially β-oxidation) to acetyl CoA.