Download The process of beta oxidation is named after the carbon atom in the

The process of beta oxidation is named after the carbon atom in the beta position of
the fatty acyl-CoA which becomes the most oxidized during the cyclic redox reactions
that remove C2 units in form of acetyl-CoA from the fatty acyl chain. The beta carbon
becomes the new carboxyl end of the shortened (n-2) fatty acyl-CoA. The oxidation
steps are strictly analogous to the reaction steps in the citric acid cycle converting
succinyl-CoA to oxaloacetate involving an initial oxidation by acyl-CoA
dehydrogenase (EC 1.3.99.3; driven by FAD reduction), an hydration by enoyl-CoA
hydratase (EC 4.2.1.17), and a second oxidation by hydroxyacyl-CoA dehydrogenase
(EC 1.1.1.35 driven by NAD+ reduction). A C2 unit is released by beta-ketothiolase
(EC 2.3.1.16) to produce acetyl-CoA and a shortened acyl(n-2)-CoA. The latter is
recycled until the acyl chain is shortened to its acetyl-CoA end product and oxidized
by the citric acid cycle enzymes.
The acyl-CoA dehydrogenase is specific for the length of the acyl chain being
oxidized. Three types of the dehydrogenase exist in mitochondria; type I (EC
1.3.99.12; long chain) which oxidizes C12-C18 fatty acids, type II (EC 1.3.99.3)
which oxidizes C4-C14 fatty acids, and type III (EC 1.3.99.2; butyryl dehydrogenase)
which oxidizes C4 and C6 acyl-CoA substrates. The energy yield per cycle is 5 mols
of ATP for each round, 2 mols per FADH2 (goes into complex II) and 3 mols per
NADH/H+ (goes into complex I). The energy balance for palmitic acid (sixteen
carbon atoms) is:
CH3(CH2)14CO-S-CoA + 7H2O +7CoA + 7FAD + 7NAD+

 8CH3-CO-S-CoA + 7FADH2 + 7NADH + 7H+
The completion of the degradation process (coenzyme oxidation) requires the citric
acid cycle which yields an additional 96 mols of ATP for all 8 acetyl-CoA units
oxidized in the process. The total energy yield of palmitic acid oxidation results in
some 130 mols of ATP, 34 units from the beta-oxidation cycle and 96 form the citric
acid cycle.
Beta oxidation of odd numbered fatty acids yields a (C2) acetyl-CoA and (C3)
propionyl-CoA end product during the very last cycle. Propionyl-CoA cannot be
further oxidized as such and is converted to methyl-malonyl-CoA by propionyl
carboxylase (EC 4.1.1.41). This is an energy consuming step using 1 mol of ATP per
mol of propionyl-CoA. The net reaction is:
propionyl-CoA + CO2 + ATP = (D/L)-methylmalonyl-CoA + ADP + Pi
The methylmalonyl is formed as racemic mixture containing equal amounts of the Dand L-enantiomer. The (D)methylmalonyl-CoA is isomerized to succinyl-CoA by
methylmalonyl CoA mutase:
(D)-methylmalonyl-CoA = succinyl-CoA
Note that this reaction is also used for the degradation of hydrocarbon side chains of
the amino acids valine, leucine, and isoleucine; (S)-methylmalonyl is the same as Lmethylmalonyl; from KEGG pathway MAP00280)
Similarly, unsaturated fatty acids need special enzymes to provide the beta
oxidation intermediate trans-D2-enoyl-CoA, the substrate of enoyl-CoA hydratase.
Desaturation can result in two unusual degradation intermediates: the cis-3- and the
cis-4-enoyl-CoA. The beta oxidation intermediate, however is a trans-2 isomer.
The cis-3-enoyl-CoA intermediate is isomerized to the trans-2 form by isomerase
(EC 5.1.2.3). The cis-4-enoyl-CoA form is converted in two steps to cis-3-enoylCoA intermediate. The first step is catalyzed by acyl-CoA dehydrogenase (the first
enzyme in the beta oxidation cycle) to form 2,4-dienoyl-CoA which in turn is
isomerized by 2,4-dienoyl-CoA reductase to cis-3-enoyl-CoA.