Biochemie (Subject) / VL Doermann (Lesson)

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Lipide

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  • Major fatty acids in plants (rape seed) 16:0 Palmitic acid - all plants 16:1Δ3trans Palmitoleic acid - all plants 16:3 Hexadecatrienoic acid - only in some species 18:0 Stearic acid - all plants 18:1Δ9cis (ω9) Oleic acid - all plants 18:2Δ9,12cis (ω6) Linoleic acid - all plants 18:3Δ9,12,15cis (ω3) α-Linolenic acid - all plants 22:1Δ11cis (ω11) Erucic acid - rape seed oil (original varieties)
  • Major fatty acids in animals (mouse, human, Drosophila) 14:0 Myristic acid - Mammals Drosophila 16:0 Palmitic acid - Mammals Drosophila 16:1 Palmitoleic acid - Mammals Drosophila 18:0 Stearic acid - Mammals Drosophila 18:1Δ9cis (ω9) Oleic acid - Mammals Drosophila 18:2Δ9,12cis (ω6) Linoleic acid - Mammals Drosophila 18:3Δ9,12,15cis (ω3) α-Linolenic acid - Mammals Drosophila 20:4Δ5,8,11,14cis (ω6) Arachidonic acid - Mammals 22:6Δ4,7,10,13,16,19cis (ω3) Docosahexenoic acid - Mammals
  • Fatty acid synthesis Fatty acid de novo synthesis: Assembly of new fatty acids from C2 units (acetyl-CoA) Acetyl-CoA Carboxylase (ACCase)acetyl-CoA -> malonyl-CoA for chain elongation Fatty acid synthesase (FAS) differently organized in bacteria, plants, animalsthe growing acyl chain is bound to ACP or to the FAS complex Fatty acid desaturation Introduction of double bonds Fatty acid elongation Chain elongation reactions (in contrast to de novo synthesis)
  • Fatty acid de novo synthesis Bacteria and plants Type FAS IIAll enzymes on different polypeptidesAcyl Carrier Protein ACPLocalization: cytosol (bacteria),plastids (plants)
  • Fatty acid de novo synthesis Animal and yeast Type FAS I:animals: α2 , Dimer of two 300 kDa polypeptidesYeast: α6β6 complex of 210 kDa polypeptidesContaining all enzymes and ACP domaineLocalization: cytosol
  • Coenzyme A (CoA-SH) 5, Cysteamin 4, β-Alanine 3, Pantoinic acid 2, Diphosphate1, 3‘-Phospho-Adenosine 4 + 3 - Pantothenic acid (vitamin B5) 5 + 4 + 3 - Panthetheine 5 + 4 + 3 + 2 - 4-Phospho-Panthetheine CoA binds acyl groups via the sulfhydrol group (SH):Thioesters represent „activated acyl groups“
  • Acyl Carrier Protein (ACP-SH) ACP is the acyl carrier during fatty acid synthesis in:BacteriaChloroplasts of plantsMitochondria of plant, yeast and animalsBut not: in the cytosol of animals ACP binds acyl groups via the sulfhydrol group (SH):Thioesters represent „activated acyl groups"
  • Fatty acid desaturation: Introduction of double bonds The desaturation reaction represents an oxidation of the acyl chain.2 electrons are released that are used for reduction of oxygene.2 further electrons required for oxygene reduction are derived from reducedferredoxin or cytochrome b5 ( redox active proteins)
  • Fatty acid elongation Acyl-CoA esters are elongated with acetyl-CoA in a cycle of reactionssimilar to fatty acid de novo synthesis C16-CoA → C18-CoA → C20-CoA → C22-CoA ... Up to C30-CoA in some organisms Fatty acid elongation is localized to the Endoplasmic Reticulum in:Plants, animals and yeast
  • Lipid breakdown: β-Oxidation of fatty acids Acyl groups are hydrolyzed from the lipids: Lipases Synthesis of Acyl-CoA esters Transport to peroxisomes (plants) or mitochondira (animals) Degradation of acyl-CoAs via β-oxidationα, β, ω positions of the acyl chain: ω: last carbon of the acyl chain β: carbon next to α carbon α: carbon next to the carboxyl carbon
  • Oxylipins (oxigenated fatty acids) (derived from monooxygenase or dioxygenase reactions on fatty acids)Monoogxgenases (Cytochrome P450 enzymes, heme containing) R-H + O2 + 2 H+ + 2 e– → R-OH + H2OAlkanes --> AlcoholsDouble bonds --> Epoxides DioxygenasesLipoxygenases: fatty acid with double bond --> hydroperoxide (C-OOH) Oxylipins have important physiological functions:Animals: Eicosanoids (derived from 20:4 or 20:5): e.g. ProstaglandinPlants: Jasmonic acid (derived from 18:3), a plant hormone
  • Jasmonic Acid, JA (Jasmonsäure) a plant hormone (phytohormone) In 1971, isolated from Jasmin Methyl Jasmonate is the mostcommon form in plants Function:inhibits growthreproduktive developmentInvolved in pathogen resistence derived from 18:3 via alipoxygenase reaction