1、10.Lipid metabolismHuangxiaoLinyi university Key notes Structures and roles of fatty acids Fatty acid breakdown Fatty acid synthesis Triacylglycerols 10.1 Structures and roles of fatty acids Fatty acids have a long hydrocarbon chain with a terminal carboxylic acid group.Most fatty acids have an even
2、 number of carbon atoms in an unbranched chain.Saturated fatty acids have no double bonds between the carbon atoms,whereas mono-and polyunsaturated fatty acids have one or more double bonds.Stearic acid(b)Fatty acids have four major biological roles:1)They are components of membranes(glycerophosphol
3、ipids and sphingolipids)2)Several proteins are covalently modified by fatty acids.3)They act as energy stores(triacylglycerols)and fuel molecules.4)Fatty acid derivatives serve as hormones and intracellular second messengers.10.2 Fatty acid breakdown Overview Activation Transport into mitochondria-o
4、xidation pathway Energy yield Ketone bodies1.overview Fatty acid breakdown brings about the oxidation of long-chain fatty acids.The fatty acids are first converted to their acyl coenzyme A derivatives and then degraded by the successive removal of two-carbon units from the end of the fatty acid as a
5、cetyl CoA.In cytosolCH3-(CH2)11-CH2-CH2-CH2-COOH Fatty acidCoASHATPAMP+PPiH2O2PiCH3-(CH2)11-CH2-CH2-CH2-COSCoA Acyl CoAAcyl CoA synthetase 2.Fatty acid activation RCOOH+CoASHRCOSCoAAcyl CoA synthetase ATPAMP+PPiMg2+H2O2Pi the reaction is irreversible fatty acid acyl CoA acyl CoA 3.3.Transport into m
6、itochondriaTransport into mitochondria longer chain acyl CoAs do not readily longer chain acyl CoAs do not readily cross the inner mitochondrial membrane,and cross the inner mitochondrial membrane,and require a specific transport mechanism.require a specific transport mechanism.RCO-SCoACoA-SH transf
7、erase(CH3)3N+-CH2CH-CH2COOHOH carnitine(CH3)3N+CH2CHCH2COOHRCO-O acylcarnitine R-COSCoA R-COSCoA H-H-SCoASCoA carnitine R-CO-carnitine R-CO-carnitineR-CO-carnitine H-H-SCoASCoA carnitine carnitine R-COSCoAR-COSCoA transferase transferase -oxidation -oxidation transferase transferaseInner mitochondri
8、al membrane4.-Oxidation pathway Oxidation(by FAD)Hydration Oxidation(by NAD+)Thiolysis oxidation acyl CoA dehydrogenaseFADFADH2 hydration RCH2C C COCoAHH trans trans 2-enoyl CoA enoyl CoA hydratase enoyl CoA hydratase H2O OHRCH2CHCH2COSCoA 3-hydroxyacyl CoA1.5ATPrespiratory chain R-CH2-CH2C-SCoA|OHR
9、CH2CHCH2COSCoA oxidation NAD+NADH+H+dehydrogenase thiolysis CH3COSCoA RCH2COSCoA （1）（）（2）（）（3）（）（4）3-ketoacyl CoARCH2CSCoA OCH2COCoA-SH ketothiolase 2.5ATPrespiratory chain round reaction Oxidation of odd-chain fatty acidRacemaseB12CH3-CH2-COCoAPropionyl CoAHOOC-CH2-CH2-CO CoASuccinyl CoA5.Energy yi
10、eld(C16:0)Palmitoyl CoA+7FAD+7NAD+7CoA-SH+7H2O 8 acetyl CoA+7FADH2+7(NADH+H+)Palmitoyl CoA+7 FAD+7 CoA+7H2O7 Reaction cycles of -Oxidation8 acetyl CoA+7 FADH2+7(NADH+H+)Summary 2.-oxidation:7FADH2:10.5(14)ATPs produced,7(NADH+H+):17.5(21)ATPs produced,3.Tricarboxylic acid cycle and oxidative phospho
11、rylation 8 acetyl CoA:80(96)ATPs produced.Total 106(129)ATPs produced 1.From palmitate to palmitoyl CoA consumed 2 ATPs 6.Ketone bodies Acetoacetate,D-3-hydroxybutytate and acetone are called ketone bodies.They are produced in the liver and provide an alternative supply of fuel for the brain under s
12、tarvation conditions or in diabetes.Do you think that the young man takes 250g of butter per day for 3 days?Really!Oh,so Stupid!there must belots of ketonebodies in his urine 10.3 Fatty acid synthesis Overview Transport into the cytosol The pathway1.Overview Fatty acid synthesis involves the condens
13、ation of two-carbon units,in the form of acetyl CoA,to form long hydrocarbon chains in a series of reactions.2.Transport into the cytosol Since fatty acid synthsis takes place in the cytosol,the acetyl CoA produced from pyruvate has to be transported out of the mitochondria.citrate oxaloacetate pyru
14、vateH H2 2O OATPATPCOCO2 2 Acetyl CoA Acetyl CoA mitochondrion cytosol citrate oxaloacetate Acetyl CoAATP,CATP,Co oASHASHADP+Pi malate pyruvateNADH+HNADH+H+NADNAD+NADP+NADPH+H+CO2malate Pyr carboxylaseFatty acid synthesis Palmitic acid is the first synthesized fatty acid from acetyl CoA.All other fa
15、tty acids are made by the modification of palmitic acid.Acetyl CoAMalonyl CoApalmitateOther fatty acids 3.The pathway1）Formation of malonyl CoAATPCO2ADP+PiBiotinacetyl CoA carboxylasemalonyl CoAKey enzyme for palmitate synthesis(allosteric enzyme)Protomer(inactive)citrate isocitratepalmitoyl CoAlong
16、 chain acyl CoAPolymer(active)(10-70 protomer)CH3COSCoAHOOC CH2COSCoA v CH3-CSCOA=OCH3-CACP=O v COA-SHACP-SH Acetyl transacylaseHOOC-CH2-CSCOA+ACP-SH HOOC-CH2-CACPO=Malonyl-ACP O=+COA-SHv CondensationCH3-C ACP+=O HOOC-CH2-CACPO=condensing enzyme CH3-C-CH2-CACPO=O=+CO2v Reduction CH3-C-CH2-CSACPO=O=+
17、NADPH+H+reductase CH3-CH-CH2-CACPO-OH=+NADP+v Dehydration CH3-CH-CH2-CACPO OH=-C-C=CO-CH3-H HACP dehydratase+H2O v Reduction-C=CO-CH3 H HACPC-=-3 2+NADPH+H+reductase CH3-CH2-CH-CACPO=+NADP+C=CO-CH3-H H Comparison between CoA and ACPCoASHNNNNNH2OCH2P-OO-OO-CH2-C-POO-OCH3H3CCH-OHCO-NH-CH2-CH2-CO-NH-CH
18、2-CH2-SHACPNHCH-CH2-C=OO-CH2-C-POO-OCH3H3CCH-OHCO-NH-CH2-CH2-CO-NH-CH2-CH2-SH4-phosphopantetheine4-磷酸泛酰巯基乙胺The comparison between synthesis of palmitateand -oxidation of fatty acid synthesis of palmitate -oxidation of fatty acid 1.Location cytosol mitochondrial matrix2.Linked to acyl carrier protein
19、 CoA with 4-phosphopantetheine with 4-phosphopantetheine3.Enzymes acetyl CoA carboxylase 4 enzymes fatty acid synthetase (multifunctional enzyme)4.2 Cs two carbons from release two carbons as malonyl CoA acetyl CoA5.Coenzymes NADPH NAD+,FAD6.Product palmitate acetyl CoA10.4 Triacylglycerols 1.breakd
20、own of triacylglycerol 1.breakdown of triacylglycerollipaseslipaseslipases 2.Oxidation of Glycerol (Glycerol can be metabolized in the liver,kidney,and intestine,but not in adipose tissue and skeletal muscle)CH2OHCHOHCH2OHglycerolgl yceroki naseATPADPCH2OHCHOHCH2O Pgl ycerol 3-phosphate -gl ycerol 3
21、-phosphate dehydrogenaseNAD+NADH+H+CH2OHC=OCH2O Pdihydroxyacetone phosphateG l ycol ysi sgluconeogenesisend GCH2OHC=OCH2O-PNADH+H+NAD+Glycerol-3-P dehydrogenaseCH2OHCCH2O-HOPCH2OCOR1CCH2O-R2CO-OPCH2OCOR1CCH2OH R2CO-O-H2OPi CH2OCOR1CCH2OCOR3R2CO-OCoA-SHR3COSCoA R1COSCoAR2COSCoA acyltransferase2 CoA-SH phosphatidic acidProblem What are the differences between -oxidation and biosynthesis of fatty acid?Describe the processes of -oxidation.
