This class Organization of cellular energy metabolism: entry of carbon fuels

1. This class Organization of cellular energy metabolism: entry of carbon fuels transport within cell metabolic interconversions in cytosol transport and oxidation in mitochondria oxidative phosphorylation

2. Energy Metabolism Which type(s) of cells produce energy?

3. Energy Metabolism Why do we need constant input of energy?

4. Energy Metabolism 3 major metabolic fuel types: Carbohydrate (glucose) Protein (amino acids) Lipids (fatty acids)

5. 1. Entry of carbon fuels: plasma membrane transport amino acids fatty acids glucose

6. 1. Entry of carbon fuels: plasma membrane transport amino acids fatty acids glucose GLUT

7. 1. Entry of carbon fuels: plasma membrane transport GLUT4 in isolated adipocytes

8. 1. Entry of carbon fuels: plasma membrane transport • GLUT protein isoforms • Same basic structure • 13 members (isoforms) now recognized • Differ in tissue specificity, kinetic properties (including sensitivity to insulin)

9. 1. Entry of carbon fuels: plasma membrane transport amino acids fatty acids glucose GLUT

10. 1. Entry of carbon fuels: plasma membrane transport amino acids fatty acids glucose GLUT

11. 1. Entry of carbon fuels: plasma membrane transport amino acids fatty acids glucose GLUT ?

12. Fatty acid transport – plasma membrane

13. Fatty acid transport via an ATP-driven pump?

14. 1. Entry of carbon fuels: plasma membrane transport • Glucose – specific transporters (GLUT) • Amino acids – diffusion and/or transporters (many!) • Fatty acids – still unknown!

15. Transport within the cell amino acids fatty acids glucose GLUT

16. Transport within the cell amino acids fatty acids glucose GLUT glucose Glucose-6P

17. Transport within the cell amino acids fatty acids glucose GLUT glucose amino acids Glucose-6P

18. Transport within the cell amino acids fatty acids glucose GLUT glucose amino acids Glucose-6P Fatty acid binding protein (FABP)

20. 2. Transport within the cell • Glucose – soluble; trapped by conversion to G-6P • Amino acids – diffusion/transport • Fatty acids - FABP

21. 3. Metabolic interconversions in the cytosol GLUT glucose Fatty acids amino acids Glucose-6P

22. 1 glucose ↓ 2 pyruvates

23. 3. Metabolic interconversions in the cytosol GLUT glucose Fatty acids amino acids Glucose-6P 2x pyruvate

24. 3. Metabolic interconversions in the cytosol GLUT glucose Fatty acids amino acids Glucose-6P lactate (2x) pyruvate mitochondria

25. 3. Metabolic interconversions in the cytosol GLUT glucose Fatty acids amino acids Glucose-6P

26. 3. Metabolic interconversions in the cytosol GLUT glucose Fatty acids amino acids Glucose-6P Transamination deamination Oxidation of carbon skeleton

27. 3. Metabolic interconversions in the cytosol GLUT glucose Fatty acids amino acids Glucose-6P Acyl-CoA synthetase Fatty acyl-CoA

28. Metabolic interconversions in the cytosol • Glucose: → pyruvate → lactate • Amino acids → trans/deamination → oxidation • Fatty acids: → fatty acyl-CoA

29. 4. Import into mitochondria & catabolism

31. Pyruvate transport & catabolism

32. Import of fatty acids into mitochondria

33. Catabolism in the mitochondrial matrix

34. Catabolism in the mitochondrial matrix

35. Import into mitochondria & catabolism • pyruvate → PyrC → PDH → TCA • amino acids: many • fatty acids → CPT →β-ox → TCA

36. Organization and compartmentalization of fuel catabolism - summary

37. The mitochondrion – energy transduction central How does it work?

40. http://www.sci.sdsu.edu/TFrey/MitoMovie.htm

43. The (in)efficiency of oxidative phosphorylation

44. Proton leak: Non-ohmic (v. high leak at high membrane potential)

45. Purpose of proton leak? Why isn’t ox-phos more efficient?

49. Purpose of proton leak? Heat production?

50. Purpose of proton leak? Heat production? (only in some cases)