1. 23-1 Principles and Applications of Inorganic, Organic, and Biological Chemistry Denniston,Topping, and Caret 4 th ed Chapter 23 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Power Point to Accompany

2. 23-2 Introduction Acetyl-CoA is a molecule preeminent in lipid metabolism. It is used in fatty acid synthesis, produced during fatty acid degradation, and used to build isoprenoid molecules. acetyl here

3. 23-3 23.1 Lipid Metabolism in Animals Triglycerides (TAGs) are emulsified into fat droplets in the intestine by bile salts from the gallbladder. Bile: micelles of lecithin, cholesterol, protein, bile salts, inorganic ions, and bile pigments. Pancreatic lipase catalyzes hydrolysis of TAGs to monoglycerides and fatty acids which are absorbed by intestinal epithelial cells, reassembled into TAGs and combined with protein to form chylomicrons which transmit TAGs to adipocytes.

4. 23-4 Stages of Digestion Insert fig 23.3 and caption

5. 23-5 Lipid Storage Fatty acids are stored in adipocytes as triglycerides in the cells cytoplasm. When energy is needed, hydrolysis converts TAGs to fatty acids which are transported to the matrix of abundant mitochondria where they are oxidized.

6. 23-6 23.2 Fatty Acid Degradation Step 1 of  -oxidation : Activation A fatty acyl CoA (thioester) is formed in two steps. The process consumes the equivalent of two ATP because two high energy phosphoric anhydride bonds are cleaved. High energy bonds cleaved

7. 23-7 Crossing to the Matrix The activated acyl group reacts with carnosine. The reaction is catalyzed by carnitine acyl transferase. The product crosses into the matrix. Acyl-CoA is regenerated in the matrix in another transesterification reaction.

8. 23-8  -oxidation-2 Acyl-CoA dehydrogenase

9. 23-9  -oxidation-3 Enoyl-CoA hydrase

10. 23-10  -oxidation-4  -hydroxyacyl-CoA dehydrogenase

11. 23-11  -oxidation-5 thiolase Bond cleaves

12. 23-12 ATP from stearic acid ATP acid to stearyl-CoA- 2 Steps 2-5 8 FADH 2 + 2ATP/FADH 2 16 ATP 8 NADH x 3 ATP/NADH24 ATP 9 Ac-CoA (to TCA cycle) 9 x 1 GTP x 1 ATP/GTP 9 ATP 9 x 3 NADH x 3 ATP/NADH81 ATP 9 x 1 FADH 2 x 2 ATP/FADH 2 18 ATP NET-----------------------------> 146 ATP

13. 23-13 23.3 Ketone Bodies A result of excess acetyl-CoA from  -oxidation. –High lipid intake and low carbohydrate intake –(not enough oxaloacetate) Starvation (body consumes fats) Diabetes (problems with carbohydrate catabolism)

14. 23-14 Ketone Bodies-2 The enzyme catalyzes the substitution of the  -carbon at the carbonyl carbon.  -C

15. 23-15 Ketone Bodies-3

16. 23-16 Ketone Bodies-4 An excess of ketone bodies is called ketosis. This condition overwhelms the buffering capacity of the blood. The body will excrete H + (and K + and Na + ) in the urine. Dehydration and a mineral imbalance result. The condition can be fatal.

17. 23-17 23.4 Fatty Acid Synthesis In the cytoplasm Acyl group carrier is acyl carrier protein (ACP). Synthesis by multienzyme complex known as fatty acid synthase. NADPH is reducing agent

18. 23-18 Condensation Acetoacetyl-ACP

19. 23-19 Step 4: First Reduction D-  -hydroxybutyryl-ACP

20. 23-20 Step 5: Dehydration Crotonyl-ACP

21. 23-21 Step 6: Second Reduction Crotonyl--ACP is end of first cycle and beginning of second cycle

22. 23-22 32.5 Regulation of Carb/Lip Metab. Liver (Carb) Insulin causes glucogenesis to occur. Glucagon stimulates breakdown of glycogen and release of glucose to bloodstream. Lactate from muscles is converted to glucose (gluconeogenesis). Liver (Lipid) Excess fuel results in fatty acids and TAGS which are transported to adipose tissue by VLDL complexes. During starvation or fasting, liver converts FAs to ketone bodies and exports them.

23. 23-23 Regulation of Carb/Lip Metab., cont. Adipose Tissue Major storage depot for fatty acids via hydrolyzed TAGs. Limited glucose means limited glycerol-3- phosphate which is essential for resynthesis of TAGs. Fatty acids and glycerol are consequently exported to the liver for further processing.

24. 23-24 Regulation of Carb/Lip Metab., cont. Muscle Tissue Resting muscle uses fatty acids for energy. Working muscle uses glycolysis. If there is a lack of oxygen, lactate is produced. It is exported to the liver for gluconeogenesis. The Brain Under normal conditions the brain uses glucose as it sole source of fuel. Under starvation conditions the brain will use acetoacetate and  -hydroxybutyrate (ketone bodies).

25. 23-25 32.6 Glucagon and Insulin Insulin is secreted in response to high blood glucose levels. Carbohydrate Metabolism Stimulates glycogen synthesis while inhibiting glycogenolysis and gluconeogenesis. Protein Metabolism Stimulates incorporation of AA into proteins Lipid Metabolism Stimulates uptake of glucose by adipose cells and synthesis of triglycerides.

26. 23-26 Glucagon and Insulin, cont. Glucagon is secreted in response to low blood glucose levels. Carbohydrate Metabolism Inhibits glycogen synthesis while stimulating glycogenolysis and gluconeogenesis. Lipid Metabolism Stimulates the breakdown of fats and ketogenesis. Protein Metabolism No direct effect.

27. 23-27 The End Fatty Acid Metabolism