Major Dietary Fuel Molecules

1. Introduction to MetabolismJoe vs. JosieJack BlazykProfessor of BiochemistryAssociate Dean for Research & Grants

2. 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 Major Dietary Fuel Molecules

3. Design of Metabolism

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

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

6. Design of Metabolism

7. Located in mitochondrial matrix HS - CoA S - CoA O = CH3 - C - 3 H2O

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. Carbohydrates e.g., Glucose C6H12O6 Lipids e.g., Palmitic Acid C16H32O2 Proteins e.g., Glycine Why are lipids our primary energy reserves? 4 Cal/g 9 Cal/g More Reduced 4 Cal/g C2H5O2N

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 Previous Nutrition Label 1440 - 1920 Cal/day

12. Body Mass Index

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

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

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

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

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

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

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

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

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

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

26. No Uptake Fasting Adipose Triglyceride Breakdown Fatty Acid Oxidation

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

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

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

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

31. O = CH3 –C– CH2– COOH OH _ CH3 –CH– CH2– COOH Palmitic Acid CH3-(CH2)14-COOH vs. Acetoacetate b-Hydroxybutyrate

32. O O = = CH3 –C– CH2– COOH CH3 –C– CH3 Acetoacetate Acetone + CO2

33. Glucose Insulin Glycogen CO2 + H2O Glucose Glucose aa aa CO2 + H2O Urea Protein Chylomicrons Pyruvate TG TG VLDL CO2 + H2O Lactate Glycogen Lactate Well-Fed State Brain Pancreas Gut Portal Vein Liver Adipose Lymphatics Muscle RBC

34. Glucose Glucagon Glycogen CO2 + H2O Glucose FA Pyruvate FA CO2 + H2O CO2 + H2O Lactate Lactate Early Fasting State Brain Pancreas Gut Portal Vein Adipose Liver Lymphatics Muscle RBC

35. Glucagon CO2 + H2O Glucose KB Glycerol Urea FA FA CO2 + H2O Pyruvate CO2 + H2O aa Protein Cortisol Lactate Extended Fasting State Brain Pancreas Gut Portal Vein Adipose Liver Lymphatics RBC Muscle

36. O O = = CH3 –C– CH2– COOH CH3 –C– CH2– COO OH OH _ _ CH3 –CH– CH2– COOH CH3 –CH– CH2– COO Acidosis Acetoacetate + + H H - pH b-Hydroxybutyrate -

37. + Compensation H - HCO3 + H2O + CO2 H2CO3 Respiration pH

38. Fig. 16-10