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 glucose amino acids fatty acids

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

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

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

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

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

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

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

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

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

18. 2.Transport within the cell glucose amino acids fatty acids GLUT Glucose-6P glucose amino acids 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. GLUT Glucose-6P glucose amino acids Fatty acids 3. Metabolic interconversions in the cytosol

22. 1 glucose ↓ 2 pyruvates

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

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

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

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

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

28. 3.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

35. 4.Import into mitochondria & catabolism pyruvate → P yrC → 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)

51. Functions of UCPs UCP1 - Only in mammals - Only in brown adipose tissue – heat production

52. Functions of UCPs Other UCPs - Ubiquitous (nearly; including ectotherms) – prevent membrane potential getting to high?

53. Purpose of proton leak? Heat production? (only in some cases) Reduce production of reactive oxygen? Rapid rest to work transitions (idling speed)?

54. Inefficiency of oxidative phosphorylation  Proton leak  Present in mitochondria from all organisms (including ectotherms)  Substantial (~20% of cellular MR)  Basal rate of leak increased by protein catalysts (UCPs) in some cell types

55. Metabolic organization of animal cells Regulated membrane transport of energy substrates Protein-mediated intracellular transport of some energy substrates Mitochondrial membrane transporters TCA cycle as a central node in catabolic pathways Proton motive force and ATP synthesis Inefficiency of ox-phos

56. Next week: Finish reading chapter 3 Read posted review