Lesson Learning Outcome

Upon completion of this lecture, students

should be able to:
 understand lipid catabolism
 Lipid catabolism
• Fatty acids are the major source of energy in catabolism of
lipids
• Sterols (eg steroids) are not catabolized but are excreted out
• Thus 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
Liberation of fatty acids from TAG in
adipose tissue is hormone-
dependant.
 Fatty Acids and Energy
• Fatty acids in triacylglycerols are the principal storage
form of energy for most organisms
– their carbon chains are in a highly reduced form
– the energy yield per gram of fatty acid oxidized is
greater than that per gram of carbohydrate oxidized

Energy
(kJ•mol -1)
C6 H1 2 O6 + 6 O 2 6 CO 2 + 6 H 2 O -15.9
Glucose
CH3 ( CH2 ) 1 4 COOH + 2 3 O 2 1 6 CO 2 + 1 6 H 2 O -38.9
Palmitic acid
Fig. 21-1, p. 592
 Activation of fatty acid
• A thioester bond is formed between the
carboxyl group of the fatty acid and the thiol
group of the CoA  acyl-CoA
– Enzyme responsible is acyl-CoA synthetase,
reaction require ATP
– Acyl-CoA can cross the outer mitochondrial
membrane but not the inner membrane
Activation of fatty acid
 Transport of Acyl-CoA
• In 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 translocase
+
O CH2 N( CH3 ) 3
RC - S C o A + H O C H C H 2 C O O-
Carnitine
+
O CH2 N( CH3 ) 3
-
RC O C H C H 2 C O O + HS -CoA
An acyl-carnitine
 Β-oxidation
 In the matrix, repeated sequence of reactions cleaves two-
carbon units from the fatty acids starting from the carboxyl
end  process called β-oxidation
 The whole cycle requires four reactions.
 Each cycle produces single molecules of FADH2,
NADH, and acetyl-CoA
 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

O acyl-CoA
  dehydrogenase
R- CH 2 -CH 2 - C-SCo A + FAD
An acyl-CoA O
H C-S Co A
C C + FAD H 2
R H
A trans enoyl-CoA
 Reaction 2: hydration of the carbon-carbon
double bond

O OH
enoyl-CoA
H C- S Co A O
+ H2 O hydratase C
C C R CH 2 - C- SCo A
R H H
A trans enoyl-CoA An L- -hydroxyacyl-CoA
 Reaction 3: oxidation of the -hydroxyl group
to a carbonyl group

OH
O -hydroxyacyl-CoA
C + dehydrogenase
H CH2 -C- SCoA + N AD
R
-Hydroxyacyl-CoA
O O
R- C-CH2 - C- SCoA + N AD H
-Keto acyl-CoA
 Reaction 4: cleavage of the carbon chain by a
reverse Claisen reaction

O O
thiolase
R- C-CH2 - C- SCoA + CoA -SH
-Keto acyl-CoA Coenzyme A

O O
R- C-SCo A + CH3 C-SCo A
An acyl-CoA Acetyl-CoA
• the overall equation for oxidation of stearic acid
can be obtained by adding the equations for b-
oxidation, the citric acid cycle, and oxidative
phosphorylation

O
CH3 ( CH2 ) 16 CSCoA + 2 6 O2 + 1 2 2 ADP + 1 2 2 Pi

1 8 CO2 + 1 7 H2 O + 1 2 2 ATP + CoA-SH

 Odd-Numbered Fatty Acids
• The last -oxidation cycle of a fatty acid with an
odd number of carbons gives propionyl-CoA
Thr Ile Met propionyl-CoA V al
carboxylase

O A TP O O
-
C H2 -C - SCo A + C O 2 O - C C H - C- S C o A
CH3 A D P + Pi CH3
Propionyl-CoA Methylmalonyl-CoA

rearrangement
O
O C H 2 -C- SC o A
TCA -
cycle O- C CH2
Succinyl-CoA
 Ketone Bodies
 Ketone bodies: substances related to acetone
 acetone, -hydroxybutyrate, and acetoacetate
 formed principally in liver mitochondria
 can 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 it
 intake high in lipids and low in carbohydrates
 diabetes not suitably controlled
 starvation
 Ketone Bodies
HS-CoA
O O O
2 CH3 C-SCoA CH3 CCH2 C- SCoA
Acetyl-CoA Acetoacetyl-CoA

O NADH OH
CH3 -C- CH2 -COO- CH3 -CH-CH2 - COO-
Acetoacetate NAD + + H + -Hydroxybutyrate

CO2 O
CH3 -C- CH3
Acetone
End of lecture