BMB 462 Lecture 9 Outline of Last Lecture I Neuronal Signaling II Regulation of Transcription by Steroid Hormone Receptors III Energy Catabolism in the 4 basic biochemical building blocks IV Energy storage in lipids V Lipid digestion absorption and transport in mammals VI Mobilization of Triacylglycerol from adipose tissue VII Glycerol Metabolism VIII Fatty Acid Catabolism Outline of Current Lecture I Continuation of Fatty Acid Catabolism a Beta oxidation of fully saturated fatty acids b ATP yield c Beta oxidation of mono and polyunsaturated fatty acids d Odd chain fatty acids e Peroxisomal beta oxidation f Other types and uses of beta oxidation II Ketone Bodies a Synthesis b Catabolism Current Lecture Concepts to remembers from previous courses lectures NAD NADH H and FAD FADH2 structures Lipoprotein Lipases lipases hydrolyze lipids and remove the fatty acids So Lipoprotein lipases specifically break down triacylglycerol in lipoproteins i e the chylomicron Shuttle systems i e the malate aspartate shuttle or the glycerol I3 dehydrogenase shuttle system I Continuation of Fatty Acid Catabolism a Beta oxidation of fully saturated fatty acids i Oxidizing the beta carbon of a fatty acid is a series of repeated oxidations These notes represent a detailed interpretation of the professor s lecture GradeBuddy is best used as a supplement to your own notes not as a substitute ii Beta oxidation removes 2 carbons as acetyl CoA 1 Acetyl CoA then moves into the Citric Acid Cycle 2 The Citric Acid Cycle reduces the coenzymes NAD and FAD to get NADH H and FADH2 These move into the Electron Chain Transport ETC and oxidative phosphorylation 3 Both NADH and FADH2 come from Beta oxidation and the Citric acid cycle a e go through the ETC to oxygen as an electron acceptor where they form H2O b At the same time a proton gradient is generated which turns ATPase in order to make ATP iii The 4 steps 1 Dehydrogenation oxidation Done by acyl CoA dehydrogenase Remove H and therefor e and oxidize the Beta Carbon creating a double bond between the alpha and beta carbons a When you oxidize something you have to have a complementary reduction reaction Here 2 H and 2 e are removed from the fatty acid and transported to FAD creating FADH2 b The CoA acts as an e sink making the fatty acid easy to oxidize This is why the fatty acid must be activated before beta oxidation occurs 2 Hydration enoyl CoA hydratase the ene in enoyl indicates a double bond in the substrate adds H2O and moves all of the oxidation from the first step to the beta carbon a This creates a hydroxyl group on the beta carbon 3 Dehydrogenation oxidation Now that all the oxidation is on the beta Carbon the cell can do a second oxidation Beta hydroxyacyl CoA dehydrogenase removes 2 e 2 H and moves them to NAD to get NADH H 4 Thiolysis thiolase aka the acyl CoA acetyltransferase cause a group transfer reaction It moves the Beta Carbon double bonded to oxygen to CoA and removes 2 carbons in the form of acetyl CoA It also adds a CoA to the new end of the fatty acid 5 Beta oxidation generates 1 FADH2 1 NADH 1 acetyl CoA and 1 acyl CoA that is now 2 carbons shorter than the initial fatty acid during the round a FADH2 and NADH move to the ETC to be oxidized so they can return to accept more e and to power the ATP synthase b Acetyl CoA goes to the Citric Acid Cycle to be oxidized further c The Acyl CoA enters the next round of Beta oxidation iv Compared with TCA Cycle The Citric Acid Cycle 1 TCA starts with succinate it has 2 fully reduced Carbons in the middle a The carbons are oxidized with succinate dehydrogenase which creates FADH2 and fumarate a molecule with a double bond 2 Fumarase adds water to move the oxidation to the beta carbon then there s a 2nd oxidation which moves e to NAD reducing it to NADH H 3 Moral When nature finds a functional process it will reuse it b ATP yield i At the end of oxidation after repeating the process the cell is left with 4 carbons This is broken into 2 acetyl CoA molecules and the catabolism via beta oxidation is complete ii Acetyl CoA yielded N 2 where N is the number of Carbons in the starting fatty acid 1 Acetyl CoA is equivalent to 1 FADH2 3 NADH and 1 GTP an ATP equivalent iii The amount of FADH2 and NADH generated N 2 1 iv FADH2 1 5 moles of ATP NADH 2 5 moles ATP c Beta oxidation of mono and polyunsaturated fatty acids i Monounsaturated fatty acids 1 The double bond is typically at the 9th Carbon so the fatty acid cannot be dehydrogenated to put a double bond between Carbon 2 and Carbon 3 since there is already a double bond between Carbon 3 and Carbon 4 2 It is impossible to have back to back double bonds 3 The cell needs to use a new enzyme to continue beta oxidation enoyl CoA isomerase a Enoyl CoA isomerase flips the double bond from position 3 to position 2 and makes it a trans bond if it was cis i Called cis trans isomerization b You now have the substrate needed for enoyl hydratase and beta oxidation can continue as normal 4 Because the dehydrogenase couldn t function 1 less FADH2 is produced in the round of beta oxidation that encountered the double bond ii Polyunsaturated fatty acids 1 A double bond on an odd carbon is addressed in the same way as a monounsaturated fatty acid 2 When beta oxidation reaches the round with a double bond on an even carbon carbon 4 at this point the round starts normally with acyl CoA dehydrogenase adding a double bond to Carbon 2 a But now there is a 2nd double bond the fatty acid is now a 2 4 diene so the hydratase can t add water b Instead 2 4 dienoyl CoA reductase reduces the carbons in the fatty acid i NADPH is used to provide e which removes 1 of the double bonds the 2nd double bond is left at position 3 c The enoyl CoA isomerase is again used to flip the double bond to position 2 and beta oxidation can now proceed normally with the hydratase 3 In eliminating the even double bond the cell uses NADPH and generates NADH and FADH2 a NADPH and NADH are energetically equivalent so the 2 cancel out iii Short cut to calculating ATP generation for unsaturated fatty acids 1 Any time there s a double bond at an odd position you generate 1 5 ATP less because one less FADH2 is produced 2 Any time there s a double bond at an even carbon you generate 2 5 ATP less because one less net NADH is produced d Odd chain fatty acids i These fatty acids i e 11 carbons long usually only occur in ruminants because bacteria in their gut make proponyl CoA ii Beta oxidation begins …
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