《中南大学-生物化学-考研课件-ch25--脂类生物合成-lipid-biosynthesis》由会员分享，可在线阅读，更多相关《中南大学-生物化学-考研课件-ch25--脂类生物合成-lipid-biosynthesis（39页珍藏版）》请在金锄头文库上搜索。
1、BiochemistryFor Speciality of Biotechnology or Bioengineering at CSUMr. XIA JinlanChapter 25 Lipid biosynthesisFatty acid synthesisSynthesis of saturated fatty acidsSynthesis and degradation of fatty acids take place in different placesDifferences between fatty acid breakdown and synthesisBreakdownS
2、ynthesisSite of actionsCytosol for prokaryotesMitochondria for eukaryotesCytosol for both prokaryotes and eukaryotesRole of NADPH or NADHNADH produced in b b-oxidationUse NADPH as the reductantLinkage of Fatty acid Fatty acid-CoAFatty acid-acyl carrier proteinUse of enzyme(s)Several individual separ
3、ate enzymesSeparate enzymes for plants and bacteriaSingle multifunctional enzyme complex-fatty acid synthase for animalsSaturated fatty acid-CoAThe general reaction (for palmitic acid synthesis)Alternatively expressed as:Fatty acid is synthesizedfrom acetyl-CoA in cytosolIn one word:Where does the a
4、cetyl-CoA come from and how does it transfer ?CytosolAcetyl-CoAAmino aciddegradationMitochondrionAcetyl-CoAFatty acidoxidationGlycolysisPyruvatecytosolRequiredcytosolMTMTMT: mitochondrionCitrate-malate-pyruvate shuttleWhy is malonyl-CoA needed ?How does it commonly form ?The first step is to form ac
5、etyl- and ,malonyl-acyl carrier proteinAcetyl transacylase is not highly specific, but not at much lower rates; malonyl transacylase is just contrary.Structures of ACP and CoA (CoASH)Acetyl-CoA carboxylase is Biotin-dependent and displays ping-pong kineticsThe carboxylation of biotinThe transcarboxy
6、lation of biotinThe carboxylation of acetyl-CoAIn animals, acetyl-CoA carboxylase is a multifunctional proteinThe ACCaseIs modulated byphosphorylation and dephosphorylationP808Also seep819More activeformThen, how does the fatty acid chain elongate and Is there also a common cycle ?The elongation cyc
7、le of fatty acid synthesisThe final product of fatty acid synthesisTotal cycles: 7The initial andcontinuation reaction of fatty acidsynthesisFor the further synthesis of C16 fatty acids, how does it process ?nCatalyzed by enzymes on smooth ER (SER)nMalonyl-CoA, rather than malonyl-ACP as the two-car
8、bon donornElongated chain as CoA derivative rather than ACP derivativeAdditional elongationIn ERHow is the fatty acid synthesis regulated ?The key enzyme: acetyl-CoA carboxylase (ACC)Regulation of ACCnShort-term effectsnCitrate activites ACC polymerizationnLong-chain fatty acids inhibit ACCnInsulin
9、stimulates de-phosphorylation and activationnGlucagon stimulates phosphorylation and inhibitionnPhosphorylation by AMP-regulated kinase which itself is phosphorylated and activated by a kinase kinase, PKA phosphorylates PPI-1 leading to reduced phosphate removal from ACCnLong-term effectsnHigh carbo
10、 and fat-free diets lead to increased synthesisnhigh-fat diets, fasting and glucagon lead to decreased synthesisSummary of the control of acetyl CoA carboxylase by Phosphorylation and allosteric regulationKey enzyme:Acetyl CoAcarboxylaseHomeworkn1, 2, 11 p850Fatty acid synthesisSynthesis of unsatura
11、ted fatty acidsAppendix: nBiosynthesis of monounsaturated fatty acids follows distinct routes in E. coli and animal cellsnAnaerobic pathway厌氧途径 for E. colinAerobic pathway好氧途径 in EukaryotesnBiosynthesis of polyunsaturated fatty acids occurs mainly in EukaryotesAnaerobic pathway for E. coliCCCOAC PH3
12、C (C H2)5C H2HH4CCCOAC PH3C (C H2)5C H2HOHH2O3-Hydroxydecanoyl-ACP dehydrase (3-羟癸酰-ACP脱水酶)COAC PC H2HH3C (C H2)5CCabbg3-hydroxy-decanoyl-ACPdehydraseHC H2C H2COAC PH3CCO-OC H2COAC PC H3(C H2)14CAC POPalmitoyl-ACP软脂酰-ACPNomal pathway forsaturated fatty acidsynthesisSaturatedfatty acidsynthesisSatura
13、tedfatty acidsynthesisCOAC P(C H2)7HH3C (C H2)5CCHCOAC P(C H2)9HH3C (C H2)5CCH3-ketoacyl-ACPsynthesis II and saturated fattyacid synthesis16 : 19-ACP16 : 0-ACP18 : 111-ACPAerobic pathway for EukaryotesBiosynthesis of polyunsaturated fatty acids occurs mainly in EukaryotesnMammals can desaturate only
14、 between the 9 position and the carboxyl end of an acyl chainnUnable to synthesize linoleic acid (亚油酸18 : 2 9, 12 ) and linolenic acid (亚麻酸18 : 3 9, 12, 15 )nTake only from diet-essential fatty acidsnStarting points for synthesis of other unsaturated fatty acids, such as arachidonate 花生四烯酸 (C20:4)，a precursor of several biologically important molecules, e.g., prostaglandins前列腺素 etc.,nPlants have the enzymes to desaturate at positions 9 , 12 and 15 arachidonate 花生四烯酸 (C20:4)，a precursor of several biologically important moleculesLinoleic acid (18 : 2 9, 12) FromLinoleic acidToArachidonic acid
