1. Introduction to Metabolism Joe vs. Josie Jack Blazyk Professor of Biochemistry Associate Dean for Research & Grants

2. Major Dietary Fuel Molecules Carbohydrates Starch, Sucrose, Lactose mostly Glucose Lipids Triglycerides Contains 3 Fatty Acids Proteins Polymer of Amino Acids Contain N in addition to C, H, O

3. Design of Metabolism

4. What is essential in our diet? Lipids Proteins Amino acids Unsaturated fatty acids Carbohydrates Glucose ??

5. How do we store our energy reserves? Carbohydrates e.g., Glucose Lipids e.g., Fatty Acids Proteins Amino acids 85% 15% <1% Glycogen Liver Muscle Triglycerides Adipose Where?

6. Design of Metabolism

7. Located in mitochondrial matrix 3 H 2 O CH 3 - C - O S - CoA HS - CoA

8. Why are lipids our primary energy reserves? 1 gram of carbohydrate = 4 Cal/g 1 gram of protein = 4 Cal/g 1 gram of fat = 9 Cal/g

9. Why are lipids our primary energy reserves? Carbohydrates e.g., Glucose C 6 H 12 O 6 Lipids e.g., Palmitic Acid C 16 H 32 O 2 Proteins e.g., Glycine More Reduced 4 Cal/g 9 Cal/g C2H5O2NC2H5O2N

10. Joe 16 yo, 5’10” tall, 160 pounds Joe eats 4000+ calories per day After 6 months, Joe weighs 210 pounds

11. Joe drinks 6 to 8 20-ounce Cokes per day 1440 - 1920 Cal/day Previous Nutrition Label

12. Body Mass Index

13. Joe Initial BMI 23.0 Final BMI 30.1 5’10” 160 lbs. 210 lbs.

14. What is happening in Joe’s liver? What is its metabolic response to feasting?

15. Glycolysis Glycogenesis Pentose Shunt Fatty Acid Synthesis Triglyceride Synthesis Well-Fed Liver

16. What is happening in Joe’s adipose tissue? What is its metabolic response to feasting?

17. Glycolysis Pentose Shunt Fatty Acid Synthesis Cholesterol Synthesis Triglyceride Synthesis Well-Fed Adipose

18. What is happening in Joe’s skeletal muscle? What is its metabolic response to feasting?

19. Well-Fed Muscle Glycogenesis

20. Josie 16 yo, 5’6” tall, 130 pounds Josie eats < 600 calories per day After 6 months, Josie weighs 105 pounds

21. Pria Power BarsChocolate Peanut Crunch Serving Size: 1 Bar = 28g Calories110 Calories From Fat 30 Amount/Serving % DV* Total Fat3.5g 5% Saturated Fat 2g10% Trans Fat 0g Sodium85mg 4% Total Carb16g 5% Dietary Fiber 1g 4% Sugars10g Protein 5g10%

22. Josie Initial BMI 21.0 Final BMI 16.9 5’6” 130 lbs. 105 lbs.

23. What is happening in Josie’s liver? What is its metabolic response to fasting?

24. Fasting Liver Gluconeogenesis Fatty Acid Oxidation Ketone Body Synthesis Glycogenolysis

25. What is happening in Josie’s adipose tissue? What is its metabolic response to fasting?

26. Fasting Adipose Fatty Acid Oxidation Triglyceride Breakdown No Uptake

27. What is happening in Josie’s skeletal muscle? What is its metabolic response to fasting?

28. Fasting Muscle Fatty Acid Oxidation Ketone Body Utilization No Uptake

29. Fasting Liver Gluconeogenesis Fatty Acid Oxidation Ketone Body Synthesis Glycogenolysis

30. Why does Josie’s liver make ketone bodies? Aren’t ketone bodies bad?

31. CH 3 -(CH 2 ) 14 -COOH Palmitic Acid CH 3 – C – CH 2 – COOH O = _ OH CH 3 – CH – CH 2 – COOH Acetoacetate  -Hydroxybutyrate vs.

32. CH 3 – C – CH 2 – COOH O = Acetoacetate CH 3 – C – CH 3 O = Acetone + CO 2

33. Insulin RBC Liver Muscle Adipose Brain Gut Portal Vein Lymphatics Glucose Glycogen Glucose CO 2 + H 2 O  Protein TG Urea Pancreas Glucose  TG Pyruvate Lactate Chylomicrons VLDL Glycogen CO 2 + H 2 O Well-Fed State

34. Glucagon RBC Liver Muscle Adipose Brain Gut Portal Vein Lymphatics Glycogen Glucose CO 2 + H 2 O Pancreas Pyruvate CO 2 + H 2 O Early Fasting State CO 2 + H 2 O FA Lactate

35. Glucagon RBC Liver Muscle Adipose Brain Gut Portal Vein Lymphatics CO 2 + H 2 O Pancreas Pyruvate CO 2 + H 2 O Extended Fasting State KB Lactate FA Glycerol FA CO 2 + H 2 O Protein  Cortisol Glucose Urea

36. CH 3 – C – CH 2 – COOH O = _ OH CH 3 – CH – CH 2 – COOH Acetoacetate  -Hydroxybutyrate _ OH CH 3 – CH – CH 2 – COO CH 3 – C – CH 2 – COO O = - - H + H + pH Acidosis

37. HCO 3 - H + pH + H 2 CO 3 H 2 O + CO 2 Respiration Compensation

38. Fig. 16-10