1. BIOC/DENT/PHCY 230 LECTURE 3

2. Fatty acids as a fuel o Fatty acids are the preferred fuel for most tissues o Fatty acids can only be metabolised aerobically o Red blood cells can’t use fatty acids as they don’t have mitochondria o Neurons can’t use fatty acids as they are unable to cross the blood brain barrier

3. Albumin-ffa tissues passive Delivery of fatty acids for fuel FABP-ffa FABP = fatty acid binding protein Transport across cell membrane

4. Fatty acid activation Fatty acids are activated for oxidation by attachment to CoA R-COO - +ATP+CoA-SH R-C-S-CoA +AMP + PP i O  G 0 ’ = -0.8kJ/mol fatty acyl-CoA

5. Transport into mitochondria

6.  -Oxidation

7. Regulation of  -oxidation In general, the catabolism of fatty acids is regulated by supply In muscle, the availability of substrates for  -oxidation can be controlled at several points: 1) Transport across the sarcolemma 2) Transport into the mitochondria 3) Hydrolysis of local fat stores

8. 1) Transport across the sarcolemma FABP pm FAT (fatty acid translocase) after fasting with exercise can translocate to membrane from vesicles translocation stimulated by muscle contraction

9. 2) Transport into the mitochondria CPT1

10. 3) Hydrolysis of local fat stores Intra-Muscular TriacylGlycerols (IMTGs) Degraded by hormone sensitive lipase (HSL)

11. Energy yield from the oxidation of palmitate (16:0) Aerobic oxidation of glucose: ~36 ATP

12. Exercise Metabolism Exercise puts significant energy demands on the body Different types of exercise require the mobilisation and differential processing of different fuels Tissue needs during exercise can be met by: 1) intracellular high energy molecules 2) local stores of fuel macromolecules 3) remote stores of fuel macromolecules 4) synthesis of fuel molecules in certain tissues

13. ATP can be generated by several metabolic pathways during exercise Glycolysis (aerobic and anaerobic)  -oxidation Creatine phosphate creatine phosphate + ADP creatine + ATP  G ~ 0 CK CK = creatine kinase

14. Fuel use is related to exercise intensity

15. The take home message: o Fatty acids are a widely used fuel  Fatty acids are catabolised by  - oxidation to yield acetyl-CoA   -oxidation is mainly regulated by the delivery of substrate o Exercise increases the requirement for ATP o Different types of exercise utilise different energy producing pathways