Question

Distinguish in biochemical detail between ?-oxidation of saturated and unsaturated fatty acids

Answer 1

Unsaturated fatty acids are more 'reactive' than their saturated analogues, and thus more susceptible to oxidation.

Fatty acids are distinguished by their long carbon skeletons. Now, keeping in mind that the end-product of beta oxidation is acetyl CoA (for fatty acids containing an even number of carbon atoms) and a mixture of acetyl CoA and propionyl CoA (for fatty acids containing an odd number of carbon atoms).

it is essential to understand that the process of oxidation involves breakage of carbon-carbon linkages. Now, the bond energy of a C-C single bond is 83 kcal per mole. The bond energy of a C=C double bond is 145 kcal per mole. This ensures that enthalpically, the energy of the pi bond is about 62 kcal per mole. This renders the multiple bond systems of unsaturated fatty acids more easily susceptible to functional group modification (oxidation via introduction of an OH group on one side of the double bond being an instance) than the C-C single bond systems in a saturated fatty acid.

In short, unsaturated fatty acids are more 'reactive' than their saturated analogues, and thus more susceptible to oxidation.

Enoyl-CoA hydratase is an enzyme that performs hydration (addition of water) across the double bond that is conjugated to the terminal carboxyl motif of an unsaturated fatty acid. To keep in mind a simple analogue, let us take Crotonic acid: CH3-CH=CH-COOH. When conjugated with Coenzyme A, a molecule of water is eliminated, forming crotonyl-CoA (a thioester: the generic name for such thioesters is Acyl-CoA). Now, Enoyl-CoA hydratase is extremely stereospecific, and will only function on the trans-isomer of the thioester, where the methyl (alkyl) group and the carboxylic acid derivative motif (the O=C--S~CoA motif) are anti to each other (keeping in mind the Neumann projection of the C=C double bond). This isomer is specifically called the trans-delta-2-enoyl CoA.

Enoyl-CoA hydratase will process trans-crotonyl-CoA and yield CH3-CH(OH)-CH(H)-CO--S~CoA.

[NOTE: 'Anti-Markovnikoff' addition of water has taken place, and conveniently so; thehydroxyl group is at a convenient location. Oxidation of the -OH group to a >C=O group is performed by another stereoselective enzyme:Hydroxy-Acyl-CoADehydrogenase (generically abbreviated to HAD). This is then processed by the enzyme ketothiolase to yield acetyl-CoA, and the Cn-2 fatty acid.]

The addition of a functionally interconvertible -OH group, whose modification to other groups is extremely facile, is a very useful strategy, and seeing its spontaneous natural use hints at the astounding chemical logic that pervades cellular chemistry.

The natural beta oxidation of saturated fatty acids also involves a process that introduces a pi bond (one degree of unsaturation; an increment of IHD by 1) and then processes the now unsaturated fatty acids in the above way.