Degradation of Fatty Acids

Occurs in Mitochondria.
Free fatty acids—also called unesterified (UFA) or
nonesterified fatty acids (NEFA) —are fatty acids
that are in the unesterified state.

In plasma, longer-chain FFA are combined with

albumin, and in the cell they are attached to a
fatty acid-binding protein, so that in fact they
are never really “free.” Shorter-chain fatty acids
are more water-soluble and exist as the un-
ionized acid or as a fatty acid anion.
Fatty acids must first be converted to an active
intermediate before they can be catabolized.
This is the only step in the complete degradation
of a fatty acid that requires energy from ATP.
In the presence of ATP and coenzyme A, the
enzyme acyl-CoA synthetase (thiokinase)
catalyzes the conversion of a fatty acid (or free
fatty acid) to an “active fatty acid” or acyl-CoA,
which uses one high-energy phosphate with the
formation of AMP and PPi.
Mitochondrial oxidation of fatty acids takes place in three
stages (In the first stage—beta oxidation—fatty acids
undergo oxidative removal of successive two-carbon units
in the form of acetyl-CoA, starting from the carboxyl end
of the fatty acyl chain.
The overall result is the conversion of the
16-carbon chain of palmitate to eight two-carbon acetyl
groups of acetyl-CoA molecules. Formation of each
acetyl-CoA requires removal of four hydrogen atoms
( two pairs of electrons and four H) from the fatty acyl
moiety by dehydrogenases.
 In the second stage of fatty acid oxidation, the
acetyl groups of acetyl-CoA are oxidized to CO2 in the
citric acid cycle, which also takes place in the
mitochondrial matrix. Acetyl-CoA derived from fatty
acids thus enters a final common pathway of
oxidation with the acetyl-CoA derived from glucose
via glycolysis and pyruvate oxidation.
The first two stages of fatty acid oxidation produce the
reduced electron carriers NADH and FADH2, which
in the third stage donate electrons to the
mitochondrial respiratory chain, through which the
electrons pass to oxygen with the concomitant
phosphorylation of ADP to ATP .The energy released
by fatty acid oxidation is
thus conserved as ATP.
The PPi is hydrolyzed by inorganic
pyrophosphatase with the loss of a further high-
energy phosphate, ensuring that the overall reaction
goes to completion.
Acyl-CoA synthetases are found in the endoplasmic
reticulum, peroxisomes, and inside and on the outer
membrane of mitochondria.
β-OXIDATION OF FATTY ACIDS INVOLVES
SUCCESSIVE CLEAVAGE WITH RELEASE OF
ACETYL-CoA.
In β-oxidation , two carbons at a time are cleaved
from acyl-CoA molecules, starting at the carboxyl
end.
The chain is broken between the α(2)- and β(3)-
carbon atoms—hence the name β-oxidation.
The two-carbon units formed are acetyl-CoA;
thus, palmitoyl- CoA forms eight acetyl-CoA
molecules.
Role of carnitine in the transport of
long-chain fatty acids through the inner
mitochondrial membrane. Long-chain
acyl-CoA cannot pass through the inner
mitochondrial membrane, but its
metabolic product, acylcarnitine, can.