10.Lipid metabolism,Huangxiao Linyi 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 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.,Fatty acids have four major biological roles: 1)They are components of membranes(glycerophospholipids 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 -oxidation pathway Energy yield Ketone bodies,1.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 acetyl CoA.,In cytosol,Acyl CoA synthetase,2.Fatty acid activation,RCOOH,+,CoASH,RCOSCoA,Acyl CoA synthetase,ATP,AMP+PPi,Mg2+,H2O,2Pi,the reaction is irreversible,fatty acid,acyl CoA,3.Transport into mitochondria,longer chain acyl CoAs do not readily cross the inner mitochondrial membrane,and require a specific transport mechanism.,RCO-SCoA,CoA-SH,transferase,(CH3)3N+,-CH2CH-,CH2COOH,OH,carnitine,(CH3)3N+,CH2CH,CH2COOH,RCO-O,acylcarnitine,R-COSCoA,H-SCoA,carnitine,R-CO- carnitine,R-CO- carnitine,H-SCoA,carnitine,R-COSCoA,transferase,- oxidation,transferase,Inner mitochondrial membrane,4.-Oxidation pathway,Oxidation(by FAD) Hydration Oxidation(by NAD+) Thiolysis, oxidation,acyl CoA dehydrogenase,FAD,FADH2, hydration,OH,RCH2,CH2,COSCoA,3-hydroxyacyl CoA,1.5ATP,respiratory chain, R-CH2 - CH2C-SCoA,|,OH,RCH2,CH,CH2,COSCoA, oxidation, thiolysis,（1）（2）（3）（4）,3-ketoacyl CoA,RCH2C,SCoA,O,CH2CO,CoA-SH,ketothiolase,2.5ATP,respiratory chain,round reaction,Oxidation of odd-chain fatty acid,Racemase B12,CH3-CH2-COCoA,Propionyl CoA,HOOC-CH2-CH2-CO CoA,Succinyl CoA,5.Energy yield(C16:0),Palmitoyl CoA + 7FAD+7NAD+ + 7CoA-SH + 7H2O 8 acetyl CoA + 7FADH2 + 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 phosphorylation8 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 starvation 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 be lots of ketone bodies in his urine,10.3 Fatty acid synthesis,Overview Transport into the cytosol The pathway,1. Overview,Fatty acid synthesis involves the condensation 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,pyruvate,H2O ATP CO2,Acetyl CoA,mitochondrion,cytosol,citrate,oxaloacetate,Acetyl CoA,ATP,CoASH,ADP+Pi,malate,pyruvate,NADH+H+,NAD+,NADP+,NADPH+H+,CO2,malate,Pyr carboxylase,Fatty acid synthesis,Palmitic acid is the first synthesized fatty acid from acetyl CoA. All other fatty acids are made by the modification of palmitic acid.,Acetyl CoA,Malonyl CoA,palmitate,Other fatty acids,3.The pathway,1）Formation of malonyl CoA,malonyl CoA,Protomer (inactive),citrate isocitrate,palmitoyl CoA long chain acyl CoA,Polymer (active) (10-70 protomer),CH3-CACP,=,O,COA-SH,ACP-SH,Acetyl transacylase,HOOC-CH2-CSCOA,Condensation,CH3-C ACP+,=,O,condensing enzyme,+CO2,Reduction,+NADPH+ + H +,reductase,+NADP+,Dehydration,CH3-CH-CH2-CACP,O,OH,=,=,-,C,-,dehydratase,+H2O,Reduction,-,-,=,-,3 2,+NADPH+H+,reductase,CH3-CH2-CH-CACP,O,=,+NADP+,Comparison between CoA and ACP,The comparison between synthesis of palmitate and -oxidation of fatty acid,synthesis of palmitate -oxidation of fatty acid,1. Location cytosol mitochondrial matrix 2. Linked to acyl carrier protein CoAwith 4-phosphopantetheine with 4-phosphopantetheine 3. Enzymes acetyl CoA carboxylase 4 enzymesfatty acid synthetase (multifunctional enzyme) 4. 2 Cs two carbons from release two carbons as malonyl CoA acetyl CoA 5. Coenzymes NADPH NAD+, FAD 6. Product palmitate acetyl CoA,