lipid metabolism - curriculum and instruction - blogfydhz.weebly.com/uploads/5/6/3/3/563349… ·...
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Lesson Learning OutcomeUpon completion of this lecture, students
should be able to:understand lipid catabolism
Lipid catabolismFatty acids are the major source of energy in
catabolism of lipidsSterols (eg steroids) are not catabolized but are
excreted outThus lipid molecules that contain fatty acids are
the ones that can be catabolized for energy production
The release of fatty acids from the glycerol backbone is done by enzyme lipases.
The release of fatty acids from triacyglycerides (TAG) in adipose tissue is hormone-controlled
Fatty Acids and EnergyFatty Acids and EnergyFatty acids in triacylglycerols are the principal
storage form of energy for most organismstheir carbon chains are in a highly reduced formthe energy yield per gram of fatty acid oxidized is
greater than that per gram of carbohydrate oxidized
C6H12O6 + 6O2
CH3(CH2)14COOH + 23O2
6CO2 + 6H2O
16CO2 +16H2O
-15.9
-38.9Palmitic acid
Glucose
Energy(kJ•mol-1)
1. Activation of fatty acidA thioester bond is formed between the
carboxyl group of the fatty acid and the thiol group of the CoA acyl-CoAEnzyme responsible is acyl-CoA synthase,
reaction require ATPAcyl-CoA can cross the outer mitochondrial
membrane but not the inner membrane
Transport of Acyl-CoATransport of Acyl-CoAIn the inter membrane space, acyl group is
transferred to carnithine by transesterification by carnitine acyltransferase (located in the inner membrane)Acyl carnitine can then cross the inner membrane
via specific transporter called carnitine translocaseCH2N(CH3)3CHCH2COO-RC-SCoA HO
O+
CH2N(CH3)3CHCH2COO-RC O
OHS-CoA
Carnitine
An acyl-carnitine+
+
+
Β-oxidationIn the matrix, repeated sequence of reactions In the matrix, repeated sequence of reactions
cleaves two-carbon units from the fatty acids starting cleaves two-carbon units from the fatty acids starting from the carboxyl end from the carboxyl end process called process called ββ-oxidation-oxidation
The whole cycle requires four reactions.The whole cycle requires four reactions.Each cycle produces single molecules of FADH2, Each cycle produces single molecules of FADH2,
NADH, and acetyl-CoA NADH, and acetyl-CoA and yields a fatty acid shortened by two carbons.and yields a fatty acid shortened by two carbons.
This series of reactions is then repeated on the shortened fatty acyl chain and continues until the entire fatty acid chain is degraded to acetyl-CoA
Reaction 1: oxidation of the , carbon-carbon single bond to a carbon-carbon double bond
R-CH2-CH2-C-SCoAO
An acyl-CoA+FAD
OHC C
C-SCoA
R H+ FADH2
A trans enoyl-CoA
acyl-CoA dehydrogenase
Reaction 2: hydration of the carbon-carbon double bond
+ H2O
An L--hydroxyacyl-CoA
COH
CH2-C-SCoARH
Oenoyl-CoAhydrataseH
C CC-SCoA
R HA trans enoyl-CoA
O
Reaction 3: oxidation of the -hydroxyl group to a carbonyl group
-Hydroxyacyl-CoA
COH
CH2-C-SCoAHR
ONAD+
R-C-CH2-C-SCoA-Ketoacyl-CoA
+NADH
-hydroxyacyl-CoAdehydrogenase+
O O
Reaction 4Reaction 4: cleavage of the carbon chain by a : cleavage of the carbon chain by a reverse Claisen reactionreverse Claisen reaction
R-C-CH2-C-SCoAO
-Ketoacyl-CoA
O+ CoA-SH
Coenzyme A
R-C-SCoAOO
+ CH3C-SCoAAn acyl-CoA Acetyl-CoA
thiolase
the overall equation for oxidation of stearic acid can be obtained by adding the equations for -oxidation, the citric acid cycle, and oxidative phosphorylation
CH3(CH2)16CSCoAO
+ 26O2 +122ADP +122Pi
18CO2 + 122ATP +17H2O + CoA-SH
Odd-Numbered Fatty AcidsOdd-Numbered Fatty AcidsThe last -oxidation cycle of a fatty acid with an
odd number of carbons gives propionyl-CoA
CH2-C-SCoA
Propionyl-CoA
ATPCO2
ADP + Pi
+CH3
OCH-C-SCoACH3
O-O-C
O
Methylmalonyl-CoA
CH2-C-SCoACH2
-O-CO
Succinyl-CoA
TCAcycle
rearrangementO
Thr Ile Met Val
Ketone BodiesKetone BodiesKetone bodies: acetone, -hydroxybutyrate, and
acetoacetateformed principally in liver mitochondriacan be used as a fuel in most tissues and organs
Formation occurs when the amount of acetyl-CoA produced is excessive compared to the amount of oxaloacetate available to react with itintake high in lipids and low in carbohydratesdiabetes not suitably controlledstarvation
Ketone BodiesKetone Bodies
CH3-C-CH3
O
CH3-C-CH2-COO-O
CH3-CH-CH2-COO-OH
2CH3C-SCoAO
CH3CCH2C-SCoAOHS-CoA O
Acetyl-CoA Acetoacetyl-CoA
Acetoacetate -Hydroxybutyrate
NADH
NAD+ + H+
CO2
Acetone
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