1. Chapter Twenty-One
Lipid Metabolism

2. Lipids are Involved in Generation and Storage of Energy
The oxidation of fatty acids (FA)in triacylglycerols are the principal storage form of energy for most organisms
Their carbon chains are in a highly reduced form
The energy yield per gram of fatty acid oxidized is greater than that per gram of carbohydrate oxidized

3. Catabolism of Lipids
Lipases catalyze hydrolysis of bonds between fatty acid and the rest of triacylglycerols
Phospholipases catalyze hydrolysis of bonds between fatty acid and the rest of phosphoacylglycerols
May have multiple sites of action

4. Fatty Acid Activation Fatty acid oxidation begins with activation
A thioester bond is formed between the carboxyl group of the FA and the thiol of CoA-SH

5. Liberation of Fatty Acids from Triacylglycerols

6. -Oxidation
-Oxidation: a series of reactions that cleaves carbon atoms two at a time from the carboxyl end of a fatty acid
The complete cycle of one -oxidation requires four enzymes
Reaction 1: Oxidation of the , carbon-carbon single bond to a carbon-carbon double bond
Reaction 2: Hydration of the carbon-carbon double bond
Reaction 3: Oxidation of the -hydroxyl group to a carbonyl group
Reaction 4: Cleavage of the carbon chain by a reverse Claisen reaction

7. -Oxidation (Cont’d)

8. b-Oxidation Gives Rise to Nine 2-Carbon Units

9. Summary
Fatty acids are activated and transported to the mitochondrial matrix for further catabolism
The breakdown of fatty acids takes place in the mitochondrial matrix and proceeds by successive removal of two-carbon units as acetyl-CoA
Each Cleavage of a two-carbon moiety requires a four-step reaction sequences called -oxidation

10. Ketone Bodies
Formation of ketone bodies occurs when the amount of acetyl-CoA produced is excessive compared to the amount of oxaloacetate available to react with it
Intake high in lipids and low in carbohydrates
Diabetes not suitably controlled
Starvation
Ketone bodies are: acetone, -hydroxybutyrate, and acetoacetate
Formed principally in liver mitochondria
Can be used as a fuel in most tissues and organs

11. Ketone Bodies (Cont’d)
Summary:
• If an organism has an excess of acetyl-CoA, it produces ketone bodies.
• This situation can arise from an excessive intake of fats compared to carbohydrates, or from diabetes.

12. Fatty Acid Biosynthesis
Biosynthesis is not exact reversal of oxidation
Biosynthetic reactions occur in the cytosol

13. Fatty Acid Biosynthesis (Cont’d)
Carboxylation of acetyl-CoA occurs in the cytosol
Catalyzed by acetyl-CoA carboxylase
Biotin is the carrier of the carboxyl group
Malonyl-CoA is key intermediate that is produced

15. Biosynthesis of Palmitate from Acetyl- and Malonyl-CoA
ACP : acetyl carrier protein

16. Biosynthesis of Palmitate from Acetyl- and Malonyl-CoA

18. Sites of Fatty Acid Metabolism in an Animal Cell

19. Comparison of FA Degradation and Biosynthesis
Summary
• Acetyl-CoA is transported to the cytosol and converted to malonyl-CoA
• The biosynthesis of FA proceeds by the addition of 2-carbon units to the hydrocarbon chain. The process is catalyzed by the fatty-acid synthase complex
Comparison of FA Degradation and Biosynthesis

20. Cholesterol Biosynthesis
All carbon atoms of cholesterol and steroids synthesized from it are derived from the two-carbon acetyl group of acetyl-CoA
Involves many reaction steps
Involvement of isoprene units are key to the biosynthesis of steroids and other biomolecules known as terpenes

21. Overall View of Cholesterol Biosynthesis

22. Squalene to Cholesterol

23. Cholesterol as a Precursor
Cholesterol is the precursor for a number of steroid hormones

24. Role of Cholesterol in Heart Disease
Lipids are transported in the blood stream by lipoproteins
Cholesterol and its fatty acid esters are packaged into several classes of lipoproteins for transport

25. The LDL Particle

26. The Fate of Cholesterol

27. Summary
The biosynthesis of cholesterol proceeds by the condensation of five-carbon isoprenoid units
Isoprenoid units in turn are derived from the reaction of three acetyl-CoA units
Once cholesterol is formed, it serves as a precursor for other steroids
Cholesterol must be packaged for transport in the bloodstream. Some of these forms of cholesterol play a role in heart disease