β-Oxidation of saturated fatty acid

β-oxidation:

β-oxidation is the removal of successive two-Carbon atoms from the Carboxyl(-COOH) end of the Fatty Acyl Chain to form two carbons containing acetyl coA.

For example, the 16-carbon containing Palmitic acid undergoes seven β-oxidation process and in each oxidative process they lose two carbons containing Acetyl CoA. Thus, the overall conversion of 16-carbon containing Palmitic acid in seven cycle produces total 8-Acetyl coA. See figure-1 (b).   

β-oxidation takes place in mitochondria in eukaryotes and in cytosol in prokaryotes.

β-oxidation mechanism was explained by Franz Knoop in 1904. Knoop experimented on the dog he fed the long chain of linear fatty acid in which a phenyl chain attached at ω-Carbon of fatty acid.
They found that the urine of dog contains derivative of phenyl acetate when they were fed by phenylbutyrate (even noₛ of carbons).

Again, when dogs are fed by phenyl propionate (odd noₛ of carbons), the derivative of benzoate were formed. In both case two carbon molecule is cleaved from the fatty acids. Thus, Knoop hypothesized from these experiments that fatty acids are degraded by oxidation at β-carbon i.e fatty acid degrades into two-carbon units this is known as Knoop's hypothesis(β-oxidation).

The β-oxidation of Saturated fatty acid has basically four steps mechanism which is illustrated in figure.1(a).

First step: α,β-Dehydrogenation of acyl CoA

In this step, palmitoyl-CoA (Acyl CoA) is oxidized by an enzyme called acyl CoA dehydrogenase and produces trans-Δ²-enoyl CoA (Δ² symbolises the position of double bond) which having trans double bonds between α and β carbon atoms (C₂ and C₃).

N.B:  Note that the double bond in enoyl coA has trans configuration whereas the double bond in natural occurring unsaturated fatty acid are normally in cis configuration.

The first step is catalysed by three isozymes (same enzymes, same catalytic activity but differ in amino acid sequences) of Acyl-CoA dehydrogenase which is present in matrix of Mitochondria. Each Acyl-CoA dehydrogenase work specifically on specific range of fatty acyl chain. Acyl-CoA dehydrogenase is analogous to succinate dehydrogenase in the citric acid cycle.

(a) SCAD (short chain Acyl-CoA dehydrogenase)-acts on fatty acid of C₄ to C₆ carbons.

(b)MCAD (Medium chain Acyl-CoA dehydrogenase)- acts on fatty acid of C₆ to C₁₄ carbons.

(c)VLCAD (very long chain Acyl-CoA dehydrogenase)-acts on fatty acid of C₁₄ to C₁₈ carbons.

All three isoenzymes are flavoprotein which contain FAD as prosthetic group.

FAD acts as electron acceptor which accept electrons when electrons are removed from fatty acyl-CoA.

(a)

(b)

Figure-1: β-oxidation cycle (a) In each pass through this four-step sequence, one acetyl residue (shaded in Green) is removed in the form of acetyl-CoA from the carboxyl end of the fatty acyl chain —in this example palmitate(C₁₆), which enters as palmitoyl-CoA. (b) 6 more molecule of acyl CoA passes through to the β- oxidation pathway yield 7 more molecules of acetyl-CoA. The seventh arising from the last two carbon atoms of the 16-carbon chain, total eight molecules of of acetyl-CoA formed.

Second step: Hydration of α-,β-acyl CoA

 In the second step, water is added to the double bond of enoyl-Δ²-CoA to form the L-stereoisomer of β-hydroxacyl-CoA(3-hydroxyacyl-CoA) by the help of enoyl-CoA hydratase. It is analogous to fumarase enzyme of citric acid cycle.

Third step: Oxidation of β-hydroxyacyl CoA

In the third step,β-hydroxyacyl CoA is dehydrogenated by the help of β-hydroxyacyl CoA dehydrogenase to form β-ketoacyl CoA. NAD+ is the electron carrier molecule. This enzyme is closely analogous to malate dehydrogenase of citric acid cycle.

Fourth step: Thiolysis of β-ketoacyl CoA

The last step is catalysed by thiol(-SH) group of enzyme Acyl-CoA acetyltransferase, also known as thiolase, it promotes thiolysis of β-ketoacyl-CoA. The thiolase enzyme cleave β-ketoacyl-CoA at C₂ and C₃ carbons. Hence their end products are acetyl CoA that is first two carbon (C₁ and C²) containing original molecule and the another is acyl CoA chains which is less than two carbon undergo again in the β-oxidation cycle.


Posted by Bharrat Bhassker.