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Fatty acid synthesis ط      Transport of acetyl CoA from mitochondria into cytoplasm

Fatty acid synthesis ط      Transport of acetyl CoA from mitochondria into cytoplasm ط      Fatty acid Synthase Complex ط      Elongation of fatty acids ط      Energetic and regulation of fatty acid synthesis                                            D4 365-71 . Introduction

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Fatty acid synthesis ط      Transport of acetyl CoA from mitochondria into cytoplasm

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  1. Fatty acid synthesis ط     Transport of acetyl CoA from mitochondria into cytoplasm ط     Fatty acid Synthase Complex ط     Elongation of fatty acids ط     Energetic and regulation of fatty acid synthesis                                            D4 365-71 

  2. Introduction 1.        The body can synthesize all FAs from sugar and AA intermediates, but not the polyunsat-FA (== double bond near CH3). 2.        Digested polyunsat-FA from diet (animal & vegetable) is distributed through the body by blood. 3.        Palmitate (straight-chain FA, 16C) is synth by ACoAC-lase and FAS-ase (multicomplex) then others are synth from it.

  3. SC-FA Synthesis fig9.6, A-CoA ACoAC (– ATP, CO2)  M-CoA Table9.2,  (+) by citrate, high carbohydrate diet, INS (dephosphorylation)    (–) by PCoA, fasting & high fat diet, GLG & AMP (phosphorylation via cAMP) fig9.7, 9.8, FAS-ase (multicomplex): A-CoA (or butyryl CoA) + ACP AT A-ACP + CoA β-KAS  A-KAS + ACP M-CoA + ACP MT M-ACP + CoA A-KAS + MACP β-KAS (+ CO2) AM-ACP + KAS β-KAR (– NADPH)  AM-ACP (red) β-HADH (+ H2O)  AM-ACP β-KAR (– NADPH)  H-ACP è repeat (elongation) P-ACP TE P + ACP fig9.9, Summary: 8 ACoA (2C) FAS-ase (– 7ATP, 14 NADPH / + 8CoA, 6H2O)  Palmitate (16C)

  4. SC-FA Synthesis ACoA, mitosol-cytosol Cyle fig9.10, Pyr (cytosol) ==> Pyr (mitosol) PC OA / Pyr PDH ACoA OA + ACoA CS Citrate (mitosol) ==> Citrate (cytosol) ATP-CL (–ATP)  OA (Pyr) + ACoA (FA) …… Summary: cycle use 8 ATP, by cytosolic ATP-CL, for 8 ACoA to synth P. cycle produce 8 NADPH, from NADH (glycolysis), for 8 ACoA to synth P. Further 6 NADPH from PPP to synth P.

  5. Modification of  Fatty acids ط      Elongation reaction of palmitic acid ط     Desaturation of fatty acids ط     Formation and modification of polyunsaturated fatty acids                                            D4 3 71 -5 

  6. Other Fatty Acids Human Synth all FAs for Palmitic Acid (PA) except polyunsaturated-FA FAs can undergo elongation, desaturation and hydroxylation: A. Elongation Reaction 1.        In End. Retic (ER): ·         carbon source: MCoA  / reducing equivalent: NADPH ·         elongation of Palmitoyl CoA  Stearate ·         in brain, more elongation up to 24 carbon 2.        fig9.11, In Mitoch: ·         carbon source: ACoA / reducing equivalent: NADPH and NADH ·         elongation of short-chain FAs, up to 16 carbon ·         reversal of β-FA oxidation (except, NADPH-linked enoyl CoA replace FAD-linked acyl CoA DH)

  7. Other Fatty Acids B. Desaturation Reaction ·         In ER: introduction of cis = (by mixed function oxidases) ·         Palmitate / Steatrate Stearoyl CoA Desaturase (=C9-10)  Palmitoleic Acid / Oleic Acid ·         fig9.12, Further = can be placed depending on tissue: Linolenic Acid in brain / Arachidonic Acid as prostaglandin precursor C. Hydroxylation Reaction ·         In mitoch: production of α-hydroxy FA (by mixed function oxidases) require O2, NADH and NADPH ·         In most tissues, act on short-chain FA (FAO) ·         In nervous system tissues, produce long-chain FA (myelin lipid) with a OH on C2 ·         Lignoceric Acid hydroxylation Cerebronic Acid

  8. Other Fatty Acids D. Modification of Palmitate during FAS-ase ·         Short-chain FAs in milk: thioesterase split acyl linkage during production of P. ·         Branced-chain FAs in waxes: MCoA MCoAC-lase (methylation)  MMCoA E. Reduction of FAs ·         Reduction of Fatty acids to fatty alcohols by 2 step NADPH-linked reactions ·         Fatty alcohols are precursors for fatty acid (ether linkage) bond in phospholipids

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