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Lactic Acid Dehydrogenase Pyruvic Acid Dehydrogenase Complex Pyruvate to ACETYL coA CC‐CoA + CO2 • Mitochondria 3 carbon Pyruvate to 2 carbon ACETYL Coenzyme A Pyruvate Acetyl CoA + CO2 + NADH + H+ CO2 to blood for excretion Acetyl CoA multiple fates #1 oxidized in mitochondria via Krebs Cycle #2 converted to fatty acid #3 may be waisted but will not be wasted 3 FFA + glycerol triglyceride adipiose tissue • Mitochondrial reactions Citric Acid Cycle • Requires oxygen • 3 carbon Pyruvate or Lactate(from glycolysis) converted to 2 carbon acetyl‐ CoA (which enters Citric Acid Cycle) and 1 molecule of CO2 (which is a waste product that has to be excreted). NADH also produced • Citric Acid Cycle consists of eight separate biochemical reactions that are directed by enzymes of mitochondrial matrix – uses: Acetyl coA (from glycolysis or FFA) and oxaloacetate to produce: • hydrogen carrier molecules for entry into electron transport system (3 NADH and FADH2) • 1 ATP from substrate • Oxaloacetate for use in same cycle again • 2 molecules of CO 2 (which is a waste product that has to be excreted) Pyruvate In mitochondrial matrix 3C Key Acetyl-CoA Oxaloacetate Carbon atom Citrate C Malate Isocitrate 6C Fumarate Ketoglutarate 1C Succinate 4C Succinyl + 4C 1C Fig. 2-11, p. 29 Oxidative Phosphorylation • ATP is synthesized using energy from electrons associated with NADH and FADH2 as they are transferred to O2 4H+ O2 2 H2O • Two protein group process: electron transport system and ATP synthase The ATP produced captures energy available in nutrients in a form that can be used by other cellular components to do “cell work” Fig. 2-12, p. 31 1 Glucose Cytosol Glycolysis 2 NADH 2 2 Pyruvate Mitochondrial matrix Pyruvate to acetate 2 NADH 2 Acetyl-CoA 6 NADH 2 turns of citric acid cycle 2 2 x 1.5 ATP/FADH2 3 10 x 2.5 ATP/NADH Oxidative phosphorylation 25 ATP Total 32 ATP 2 FADH2 2 FADH2 Electron transfer 10 NADH Mitochondrial inner membrane Electron transfer Fig. 2-13, p. 32 Fatty Acid to Acetyl coA • • What is a fatty acid? Beta oxidation is the process by which fatty acids, in the form of Acyl-CoA molecules, are broken down in mitochondria to generate Acetyl-CoA, a. Activation of fatty acids in the cytosol b. Transport of fatty acids into mitochondria a. Fatty acids are transported across the outer mitochondrial membrane by carnitine-palmitoyl transferase I b. They are then couriered across the inner mitochondrial membrane by carnitine c. Beta oxidation occurs in the mitochondrial matrix: Two-carbon molecules acetyl-CoA are repeatedly cleaved from the fatty acid. a) Acetyl-CoA can then enter the TCA cycle, which produces NADH and FADH2. b) NADH and FADH2 are subsequently used in the electron transport chain to produce ATP What is a fatty acid? A fatty acid is a with a long unbranched carbon chain tail Most naturally occurring fatty acids have a chain of four to 28 carbons. The number of carbon atoms is usually even. Pictured is a rough representation of a C16 fatty acid. Activation: in cytolsol ATPADP + activated *C on fatty acid The acid and activated carbon are cleaved in a series of reactions. End products of step of 1 cycle of beta oxidation are Acetyl CoA, NADH+H+ and FADH2 and an activated fatty acid that is 2 carbons shorter ATP after 1 cycle NADH+H+ 2.5 ATP + 1 H2O FADH2 1.5 ATP + 1 H2O Acetyl CoA(KREBS CYCLE) 3 NADH+H+ , 1 FADH2 + 1ATP • 3 NADH+H+ 9ATP + 3 H2O • 1 FADH2 2ATP + 1 H2O • TOTAL = 10 ATP per Acetyl CoA entering Krebs Cycle 14 ATP produced, 1 spent , NET = 13 16C FATTY ACID • • • 8 ACETYL CoA 7 NADH+H+ 7 FADH2 (x 10 = 80 ATP) (x 2.5 = 17.5 ATP) (x 1.5 = 10.5 ATP) _____________________________________ TOTAL 108 ATP – 1 for activation = NET 107 ATP Amino Acid oxidation • transamination (or aminotransfer): reaction between an amino acid and a keto acid transminase amino acid1 + ketoacid2 ketoacid1 + amino acid2 The former keto acid is now a nonessential amino acid that has the amino group The former amino acid is now a keto acid that can be used in the Krebs cycle Deamination • Deamination is the process by which amino acids are broken down there is an excess of protein intake. The amino group is removed from the amino acid and converted to ammonia. • The rest of the amino acid is made up of mostly carbon and hydrogen, and is recycled or oxidized for energy. Ammonia is toxic to the human system, and enzymes convert it to urea or uric acid by addition of carbon dioxide molecules urea cycle, which also takes place in the liver. Urea and uric acid can safely diffuse into the blood and then be excreted in urine. Urea cycle deaminase +