Lipid Catbolism
Lipid Catbolism
Lipid Catbolism
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
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
O NADH OH
CH3 -C- CH2 -COO- CH3 -CH-CH2 - COO-
Acetoacetate NAD + + H + -Hydroxybutyrate
CO2 O
CH3 -C- CH3
Acetone
End of lecture