BBMB 405 1nd Edition Lecture 12 Outline of Last Lecture XIV Chapter 22 Fatty Acid Metabolism C Unsaturated and odd chain fatty acids require additional steps for degradation Outline of Current Lecture XIV Chapter 22 Fatty Acid Metabolism D Fatty acids are synthesized by fatty acid synthase FAS E Elongation and unsaturation of fatty acids are accomplished by accessory enzyme systems Current Lecture XIV Chapter 22 Fatty Acid Metabolism D Fatty acids are synthesized by fatty acid synthase FAS 1 Handout 2 6 De Novo Fatty Acid Synthesis takes place in adipose or liver or both depending on the type of animal liver is principal anatomical site for de novo 2 Fatty acids are synthesized and degraded by different pathways a Synthesis in cytosol degradation in mitochondria b Intermediates during synthesis linked to acyl carrier protein ACP intermediates during oxidation attached to CoA c Synthesis catalyzed by FAS serval enzymes for oxidation multifunctional enzyme d Synthesis from malonyl ACP from acetyl CoA and driven by release of CO 2 oxidation releases acetyl CoA e Synthesis uses NADPH as reductant oxidations uses NAD and FAD as oxidants f Synthesis concludes with palmitate oxidation with acetyl CoA 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 3 Formation of malonyl CoA is committed step in fatty acid synthesis rate limiting step uses acetyl CoA carboxylase to drive reaction 4 Intermediates in FAS are attached to acyl carrier protein ACP 5 Fatty acid synthesis consists of a series of condensation reduction dehydration and reduction reactions reverse reaction of beta oxidation a Where is acetyl CoA made Mitochondria But fatty acid synthesis occurs in the cytosol so need to get acetyl CoA out of mitochondria b 6 Fatty acids are synthesized by multifunctional enzyme complex in animals don t memorize catalytic cycle of mammalian fatty acid synthase 7 The synthesis of palmitate requires 8 molecules of acetyl CoA 14 molecules of NADPH and 7 molecules of ATP a Overall reaction b 8 Citrate carries acetyl groups from mitochondria to the cytoplasm for fatty acid synthesis a ATP citrate lyase Ciitrate ATP CoA H2O acetyl CoA ADP Pi OAA b c Notes on diagram i Cytoplasm everything in cell except nucleus includes mitochondria should be cytosol ii Glucose is converted to pyruvate which can come in in the bottom lef iii Malic Enzyme ME decarboxylation of malate to pyruvate iv Ruminant metabolically set up to not use glucose as precursor to fatty acid Make own glucose at premium Malic enzyme is not present so malate reenters mitochondria Free acetate can be activated by converting to acetyl CoA and come into cycle 9 Several sources supply NADPH for fatty acid synthesis a Malic enzyme Malate NADP pyruvate CO2 NADPH b Pentose phosphate pathway c NADPH isocitrate dehydrogenase isocitrate NADP alpha ketoglutarate NADPH d 10 Fatty acid synthase inhibitors may be useful drugs 11 Handout 2 9 a Fatty Acid desaturation i Desatuartion delta4 delta5 delta6 fatty acid desaturases no double bonds above 9 in desaturases in animals so no delta12 or detla15desaturases ii Essential fatty acids we cannot make we eat then make C18 2delta9 12 C18 3delta9 12 15 b Why are C18 2delta9 12 and C18 3delta9 12 15 essential i Eicosanoid synthesis as precursor ex proteglandens ii Normal membrane structure and function iii Eicosapentaenoic acid EPA C20 5delta5 11 14 17 iv Docosahexaenoic acid DHA C22 6delta4 7 10 13 16 19 v DHA and EPA prevalent in brain tissue and eyes DHA in breast milk and can slow down cancer growth c FA elongation use elongase several reactions attached to the endoplasmic reticulum d FA desaturation can only place double bond at 4 5 6 9 e Example of elongation and desaturation f i Start C18 2delta9 12 ii Delta6 desaturase iii C18 3delta6 9 12 iv Elongase v C20 3delta8 11 14 vi Delta5 desaturase vii C20 4delta5 8 11 14 arachiolonic acid Plant desaturases use phospholipid E Elongation and unsaturation of fatty acids are accomplished by accessory enzyme systems 1 Membrane bound enzymes generate unsaturated fatty acids a b How to get cytosol NADPH ME gives one provides 50 of need to make fatty acid from glucose ruminates use pentose phosphate pathway and isocitratdehydrogenase replaces need for ME c d e Oleoic acid 18 1 in adipose and not palmitic acid 16 0 but palmitic acid is synthesized the most by FAS f Desaturase places at delta9 to form oleoyl two electrons added to oxygen 2 Eicosanoid hormones are derived from polyunsaturated fatty acids a Arachidonate is major precursor of eicosanoid hormones b Control de novo inhibits FA synthase FAS in cancer patients is high so begin tested as chemotherapeutic drug
View Full Document
Unlocking...