Dr. Prabhakar Singh SEM-III_Fatty Acid Oxidation

1. Metabolism of Lipids
Lipids: Introduction, hydrolysis of triacylglycerols; oxidation of fatty acids.
Oxidation of odd numbered fatty acids, fate of propionate, role of carnitine, degradation of
complex lipids.

2. Lipids: Introduction

3. Hydrolysis of Triacylglycerols

5. FATTY ACID OXIDATION
A. Fatty Acid Activation
B. Transport Across the Mitochondrial Membrane
C. ẞ-Oxidation

8. Source ATP Total
7 FADH2 x 1.5 ATP = 10.5 ATP
7 NADH x 2.5 ATP = 17.5 ATP
8 acetyl CoA x 10 ATP = 80 ATP
Activation = -2 ATP
NET = 106 ATP

9. Oxidation of odd numbered fatty acids/ fate of propionate,

10. α-Oxidation of fatty acids
Alpha-oxidation of phytanic acid is
believed to take place entirely
within peroxisomes.
1. Phytanic acid is first attached
to CoA to form phytanoyl-CoA.
2. Phytanoyl-CoA is oxidized
by phytanoyl-CoA dioxygenase, in
a process using Fe2+ and O2, to
yield 2-hydroxyphytanoyl-CoA.
3. 2-hydroxyphytanoyl-CoA is
cleaved by 2-hydroxyphytanoyl-
CoA lyase in a TPP-dependent
reaction to form pristanal
andformyl-CoA (in turn later broken
down into formate and eventually
CO2).
4. Pristanal is oxidized by aldehyde
dehydrogenase to form pristanic
acid (which can then
undergo beta-oxidation).

11. Peroxisomes and Fatty Acids Oxidation
Peroxisomes are small, membrane-enclosed organelles (Figure 10.24) that contain enzymes involved in a
variety of metabolic reactions, including several aspects of energy metabolism.

12. Omega oxidation
Omega oxidation (ω-oxidation) is a process of fatty acid metabolism in some species of animals. It is an alternative pathway to beta
oxidation that, instead of involving the β carbon, involves the oxidation of the ω carbon (the carbon most distant from the carboxyl
group of the fatty acid). The process is normally a minor catabolic pathway for medium-chain fatty acids (10-12 carbon atoms), but
becomes more important when β oxidation is defective.
In vertebrates, the enzymes for ω oxidation are located in the smooth ER of liver and kidney cells, instead of in the mitochondria as
with β oxidation. The steps of the process are as follows:
Reaction type Enzyme Description
Hydroxylation
mixed function
oxidase
The first step introduces a hydroxyl group onto the ω carbon. The oxygen for the group
comes from molecular oxygen in a complex reaction conduced by certain members of the
CYP4A and CYP4F subfamilies viz., CYP4A11,CYP4F2,and CYP4F3 or by two other CYP450
enzymes, CYP2U1 andCYP4Z1, that involves cytochrome P450 and the electron
donor NADPH.
Oxidation
alcohol
dehydrogenase
The next step is the oxidation of the hydroxyl group to an aldehyde by NAD+.
Oxidation
aldehyde
dehydrogenase
The third step is the oxidation of the aldehyde group to a carboxylic acid by NAD+. The
product of this step is a fatty acid with a carboxyl group at each end.

14. BIOSYNTHESIS OF FATTY ACIDS
l.' Productionof acetyl CoA and NADPH
ll. Conversionof acetylCoA to malonyl CoA
lll. Reactionsof fatty acid synthasecomplex

18. Fatty acid synthase complex

19. FAS

20. Oxidation of Unsaturated fatty acids
β-Oxidation of unsaturated fatty acids poses a problem since the
location of a cis bond can prevent the formation of a trans-Δ2 bond.
These situations are handled by an additional two enzymes, Enoyl
CoA isomerase or 2,4 Dienoyl CoA reductase.
Whatever the conformation of the hydrocarbon chain, β-oxidation
occurs normally until the acyl CoA (because of the presence of a
double bond) is not an appropriate substrate for acyl CoA
dehydrogenase, or enoyl CoA hydratase:
•If the acyl CoA contains a cis-Δ3 bond, then cis-Δ3-Enoyl CoA isomerase will convert
the bond to a trans-Δ2 bond, which is a regular substrate.
•If the acyl CoA contains a cis-Δ4 double bond, then its dehydrogenation yields a
2,4-dienoyl intermediate, which is not a substrate for enoyl CoA hydratase. However,
the enzyme 2,4 Dienoyl CoA reductase reduces the intermediate, using NADPH,
into trans-Δ3-enoyl CoA. As in the above case, this compound is converted into a
suitable intermediate by 3,2-Enoyl CoA isomerase.
To summarize:
•Odd-numbered double bonds are handled by the isomerase.
•Even-numbered double bonds by the reductase (which creates an odd-numbered
double bond)