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)

Fig. 21-1, p. 592

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