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BIOC/DENT/PHCY 230 LECTURE 3 Fatty acids as a fuel Fatty acids are the preferred fuel for most tissues Fatty acids can only be metabolised aerobically Red blood cells can’t use fatty acids as they don’t have mitochondria Neurons can’t use fatty acids as they are unable to cross the blood brain barrier Delivery of fatty acids for fuel Albumin-ffa passive tissues Transport across cell membrane FABP-ffa FABP = fatty acid binding protein Fatty acid activation Fatty acids are activated for oxidation by attachment to CoA O R-COO-+ATP+CoA-SH fatty acyl-CoA R-C-S-CoA +AMP + PPi DG0’= -0.8kJ/mol Transport into mitochondria b-Oxidation Regulation of b-oxidation In general, the catabolism of fatty acids is regulated by supply In muscle, the availability of substrates for b-oxidation can be controlled at several points: 1) Transport across the sarcolemma 2) Transport into the mitochondria 3) Hydrolysis of local fat stores 1) Transport across the sarcolemma FABPpm after fasting with exercise FAT (fatty acid translocase) can translocate to membrane from vesicles translocation stimulated by muscle contraction 2) Transport into the mitochondria CPT1 CPT1 3) Hydrolysis of local fat stores Intra-Muscular TriacylGlycerols (IMTGs) Degraded by hormone sensitive lipase (HSL) Energy yield from the oxidation of palmitate (16:0) Aerobic oxidation of glucose: ~36 ATP 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 ATP can be generated by several metabolic pathways during exercise Glycolysis (aerobic and anaerobic) b-oxidation Creatine phosphate creatine phosphate + ADP CK = creatine kinase CK creatine + ATP DG ~ 0 Fuel use is related to exercise intensity The take home message: Fatty acids are a widely used fuel Fatty acids are catabolised by boxidation to yield acetyl-CoA b-oxidation is mainly regulated by the delivery of substrate Exercise increases the requirement for ATP Different types of exercise utilise different energy producing pathways