Fat Metabolism
Transcription
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_metabol ism/fatty_acid_metabolism.htm • FUN! Activation and Transported to Mitochondria • FA + CoASH --> ATP = FA-SCoA + AMP + Ppi • Driven by breakup of Ppi • Acyl CoA Synthetase • -32.5 kJ • Transported through inner mitochondrial membrane via carnitine – uses specific acyl carnitine transporter Carnitine CH3 H3C O + N CH2 CH CH2 C CH3 OH O Formation of acyl carnitine CH3 H3C N CH2 CH CH2 C CH3 carnitine OH O CH3 O O + + CoAS C R H3C CH3 acyl CoA O + N CH2 CH CH2 C O + O C O R acyl carnitine • Can get transported across inner mitochondrial membrane CoASH 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 --> Krebs 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 O acyl-CoA R CH2 CH2 CH2 C S-CoA R CH2 C CH3 S-CoA C S-CoA FAD Acyl-CoA Dehydrogenase FADH2 HSCoA thiolase O beta-enoyl CoA O O R CH CH CH2 C S-CoA R CH2 C CH2 beta-ketoacyl CoA H2O enoyl-CoA hydratase beta-hydroxyacyl-CoA dehydrogenase O OH R CH2 CH CH2 C NADH NAD+ S-CoA beta hydroxyacyl CoA C S-CoA Reactions of Beta Oxidation Acyl-CoA Dehydrogenase FAD O R CH2 CH2 CH2 C FADH2 O R S-CoA CH CH CH2 Acyl-CoA Dehydrogenase acyl-CoA beta-enoyl CoA – Puts in a ß double bond • Oxidizes C-C bond to double bond – Produces FADH2 C S-CoA Reactions of Beta oxidation Enoyl CoA Hydratase H2O OH O R CH CH CH2 C R S-CoA CH2 CH O CH2 enoyl-CoA hydratase beta-enoyl CoA • adds water – forms ß-hydroxy product beta-hydroxyacyl CoA C S-CoA Reactions of Beta Oxidation ß-hydroxylacyl-CoA dehydrogenase OH R CH2 CH NAD+ O CH2 C NADH R S-CoA O O CH2 C CH2 C beta-hydroxyacyl-CoA beta-hydroxyacyl CoA dehydrogenase • oxidizes secondary alcohol to ketone – Oxygen-containing group – Produces NADH beta-ketoacyl CoA S-CoA Reactions of Beta Oxidation Acyl-CoA acetyltransferase (thiolase) O acetyl CoA O O CH3 C S-CoA HSCoA R CH2 C CH2 C S-CoA O beta-ketoacyl CoA R CH2 C thiolase acyl CoA • Uses another CoA • Produces Acetyl CoA • Acyl CoA can go another round S-CoA 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 2 1 3 4 6 5 8 7 O CH3 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 C 7 6 O 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