Beta Oxidation Part I The break down of a fatty acid to acetyl-CoA units…the ‘glycolysis’ of fatty acids Occurs in the mitochondria Exemplifies Aerobic Metabolism at its most powerful phase STRICTLY AEROBIC Acetyl-CoA is fed directly into the Krebs cycle Overproduction causes KETOSIS

Schedule of Topics Digestion, absorption and transport General mechanism of fatty acid oxidation Oxidation of unsaturated fatty acids Odd chain fatty acids…role of vitamin B12 Ketone bodies and ketosis Fatty Acid Oxidation

CH 3 CH 2 CH 2 COOH [CH 3 CH 2 CH 2 CO-AMP] CH 3 CH 2 CH 2 CO~SCoA HS-CoA Fatty acyl CoA ATP PP i AMP Fatty acyl CoA Ligase Prepares a Fatty Acid for transport and metabolism

Transport into Mitochondria depends on Carnitine FA~CoA FA~Carnitine Acyl transferase I FA~CarnitineCarnitine Acyl transferase II Translocase HS-CoA FA~CoA HS-CoA Carnitine N(CH 3 ) 3 CH 2 H-C-OH COO - CH 2 + Carnitine

CH 3 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 C~SCoA O CH 3 C~SCoA O O O O Beta Oxidation 8 carbon Fatty Acid Acyl-CoA 4 two carbon Acetyl-CoAs

Knoop’s Experiment PhenylacetateBenzoate

 Round Dehydrogenase Hydratase Dehydrogenase Acyl Transferase FAD H2OH2O NAD + CH 3 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 C~S-CoA O -C=C-C~S-CoA H H O -C- CH 2 -C~S-CoA OO O H H O -C…...CH 3 -C~S-CoA O O R S-CoA MECHANISM TRANS L- Cofactor or Substrate HS-CoA

Trans L Vania When you think of beta oxidation

C 6 H 12 O 6 + 6O 2  6CO 2 + 6H 2 O  H o = -2,813 kJ/mol = Cal/mol = 3.74 Cal/gram C 18 H 36 O O 2  18CO H 2 O  H o = -11,441 kJ/mol = - 2,737 Cal/mol = 9.64 Cal/gram THE ENERGY STORY PART I Glucose Stearic Acid On a per mole basis a typical fatty acid is 4 times more energy rich that a typical hexose

Energy Story Part II 1.0 g glucose = 3.7 kcal (15.5 kJ) 1.0 g stearic acid = 9.7 kcal (40.5 kJ) Stearic Acid (C18 satd) 9 Acetyl CoA= 108 ATP(90) 8 FADH 2 = 16 ATP(24) ENERGY CONSERVATION 8 NADH= 24 ATP(20) = 148 ATP(134) - 1 ATP ATP(133) Textbook

Palmitoyl-CoA (Textbook) Palmitoyl-CoA + 7CoA + 7FAD + 7NAD + + 7H 2 O 8 Acetyl-CoA80 ATP 7 FADH ATP 7 NADH + 7H ATP 108 ATP

Octoyl-CoA + 3HSCoA + 3FAD + 3NAD + + 7H 2 O CH 3 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CO~SCoA HS-CoA FAD NAD + 4 Acetyl-CoA 40 ATP R-1R-2R-3 C-8 3 FADH24.5 ATP 3 NADH + 3 H ATP 52 ATP HS-CoA FAD NAD + HS-CoA FAD NAD +

CH 3 CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 CO~SCoA CH 3 CH 2 CH 2 CH 2 CH 2 CO~SCoA CH 3 CH 2 CH 2 CO~SCoA CH 3 CO~SCoA FAD NAD HSCoA FAD NAD HSCoA FAD NAD HSCoA 11 22 33

Hexanoic acid (C 6 H 12 O 2 ) Glucose (C 6 H 12 O 6 ) Hexanoic acid Hexanoyl-CoA-1 ATP Glucose 2 pyruvates2 ATP Hexanoyl-CoA 3 Acetyl-CoA30 ATP 2 pyruvates 2 Acetyl-CoA20 ATP 2 FADH 2 3 ATP 2 NADH + H + 5 ATP 37 ATP 32 ATP 2 NADH + H + 5 ATP Mwt = 116Mwt = 180 ATP per Gram = 0.32 ATP per Gram = 0.17