Fat Metabolism

Fat Metabolism I’m not fat, I’ve just got a lot of potential energy! Digestion, Mobilization, and Transport • http://courses.cm.utexas.edu/emarcotte/ch339k/fall2005/Lecture-Ch17-1/Slide2.JPG Emulsification • Fats are not water soluble • Made into bile salts that are • Absorbed as micelles in small intestines Chylomicron Carriers • proteins that carry fats • stored in adipose tissue Role of Hormones • Can mobilize from adipose • Release as Fatty acids • Epinephrene and glucagon release cAMP – make fatty acids and glycerol – mobilizes fat Animation of Process • http://www.wiley.com/legacy/college/boyer /0470003790/animations/fatty_acid_metabo lism/fatty_acid_metabolism.htm • FUN! Activation and Transported to Mitochondria • • • • • FA + CA --> ATP = FA-CoA + AMP + Ppi Driven by breakup of Ppi Acyl CoA Synthetase -32.5 kJ Transported through inner mito membrane via carnitine – uses specific acyl carnitine transporter Carnitine CH 3 H 3C N + O CH 2 CH CH 2 C OH O CH 3 Formation of acyl carnitine CH3 H3C N CH2 CH CH2 C CH3 carnitine OH O + O O CH3 R H3C N CH2 CH CH2 C CH3 O O C R O + + O CoAS C + CoASH acyl CoA acyl carnitine • Can get transported across inner mitochondrial membrane Animation of Process • http://www.brookscole.com/chemistry_d/te mplates/student_resources/shared_resources /animations/carnitine/carnitine1.html Beta Oxidation • Breakdown of fats into – Acetyl coenzyme A --> Kreb Cycle – FADH2 --> Oxidative Phosphorylation – NADH--> Oxidative Phosphorylation • Breaks off two carbons at a time to acetyl CoA – Remaining goes another round Reactions Diagram acetyl CoA O O acyl-CoA R CH2 CH2 CH2 C S-CoA R CH2 C S-CoA CH3 C S-CoA O FAD Acyl-CoA Dehydrogenase FADH2 thiolase HSCoA O beta-enoyl CoA O R CH CH CH 2 C S-CoA R CH2 C CH2 O C S-CoA beta-ketoacyl CoA H2 O enoyl-CoA hydratase beta-hydroxyacyl-CoA dehydrogenase NADH NAD+ beta-hydroxyacyl CoA Reactions of Beta Oxidation Acyl-CoA Dehydrogenase O FAD FADH2 O R CH CH CH 2 C S-CoA R CH2 CH2 CH2 C S-CoA Acyl-CoA Dehydrogenase acyl-CoA beta-enoyl CoA – Puts in a ß double bond • Oxidizes C-C bond to double bond – Produces FADH2 Reactions of Beta oxidation Enoyl CoA Hydratase H2O O R CH CH CH 2 C S-CoA enoyl-CoA hydratase OH R CH2 CH CH2 O C S-CoA beta-enoyl CoA beta-hydroxyacyl CoA • adds water – forms ß-hydroxy product Reactions of Beta Oxidation ß-hydroxylacyl-CoA dehydrogenase OH R CH2 CH CH2 O C S-CoA NAD+ NADH O R CH2 C CH2 O C S-CoA beta-hydroxyacyl-CoA beta-hydroxyacyl CoA dehydrogenase beta-ketoacyl CoA • oxidizes secondary alcohol to ketone – Oxygen-containing group – Produces NADH Reactions of Beta Oxidation Acyl-CoA acetyltransferase (thiolase) O acetyl CoA O R CH2 C CH2 O CH3 C S-CoA HSCoA C S-CoA O beta-ketoacyl CoA thiolase R CH2 C S-CoA acyl CoA • Uses another CoA • Produces Acetyl CoA • Acyl CoA can go another round Overall Per Beta Oxidation cycle • 1 FADH2…………………………1.5 ATP • 1 NADH………………………….2.5 ATP • 1 Acetyl CoA to Krebs – 3 NADH X 2.5 ATP / NADH………7.5 ATP – 1 FADH2…………………………….1.5 ATP – 1 GTP………………………………..1.0 ATP Total = 14.0 ATP Beta Oxidation on 16 C fatty Acid O CH3 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 C O Beta Oxidation on 16 C fatty Acid 1 2 3 4 5 6 7 8 O O CH3 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 C 7 6 3 5 4 2 1 • 7 rounds of Beta oxidation (bottom numbers) • Form 8 acetyl Co A (top numbers) Beta Oxidation on 16 C fatty Acid totals • 7 rounds of beta oxidation 7 rounds X FADH2 X 1.5 ATP round FADH2 7 rounds X NADH X 2.5 ATP round NADH 8 acetyl CoA 8 Krebs 8 Krebs X 3 NADH X 2.5 ATP Krebs NADH 8 Krebs X FADH2 X 1.5 ATP Krebs FADH2 8 Krebs X GTP X 1 ATP Krebs GTP 1 ATP used to activate Total = 10.5 ATP = 17.5 ATP = 60 ATP = 12 ATP = 8 ATP = - 1 ATP 107 ATP Unsaturated Fat Metabolism • special enzymes needed to convert cis bonds in fatty acids to trans bonds Regulation of Fat Metabolism • Transport is rate-limiting • Regulation of carnitine acyl transferase – off by fat synth products – high NADH Ketone Bodies • Starvation causes accumulation of acetyl CoA – not enough carbohydrates to keep Kreb’s Cycle going – acetyl CoA forms acetoacetate, bhydroxybutyrate, and acetone. • http://www.biocarta.com/pathfiles/ketonebo diesPathway.asp Diabetes and Ketone Bodies • When there is not enough insulin in the blood and it must break down fat for its energy. • Ketones build up in the blood and then spill over into the urine so that the body can get rid of them. Acetone can be exhaled through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. (Diabetic ketoacidosis) Comparison of Fat Metabolism per gram and CHO per gram • Fats provide about 9 kilocalories per gram and carbohydrates provide about 4 kilocalories per gram. • Using nutritional units, that is 9 Calories/gram for fats and 4 Calories/gram for carbohydrates. • CHO provide energy more quickly • Fats are good fuel for endurance events, but not sprints