Oxidation of Unsaturated Fatty Acids

Introduction

Fatty acids occur as saturated and unsaturated (with one or more double bonds) fatty acids. Fatty acids majorly in triacylglycerols and phospholipids are present as unsaturated fatty acids in plants and animals.Saturated fatty acids undergo β-oxidation as described in detail here Oxidation of Fatty Acids but unsaturated fatty acids have a slight variation in the pathway. β-oxidation pathway for unsaturated fatty acids includes two additional enzymes isomerase and reductase. The complete β-oxidation pathway for unsaturated fatty acids is described below in detail.

β-Oxidation of Unsaturated Fatty Acids

Let us consider an example of monounsaturated fatty acid such as oleic acid and a polyunsaturated fatty acid such as linolenic acid. Oleic acid is an 18 carbon chain length fatty acid with a cis double bond present between the ninth and the tenth carbons. Linolenic acid is an 18 carbon chain length fatty acid with 2 cis double bonds between 9th and 10th carbons & 12th and 13th carbons.

Just like the saturated fatty acids cross the mitochondrial membrane with the help of carnitine shuttle (For more details read Activation and Transportation of Fatty acids via Carnitine Shuttle), unsaturated fatty acids also reach the mitochondrial matrix as fatty acyl-CoA. The process of β-oxidation of oleic acid and linolenic acid by the enzymes present in the mitochondrial matrix is as shown below in the diagrams.

β-Oxidation of Monounsaturated Fatty Acid

Oxidation of monounsaturated fatty acids

Oxidation of monounsaturated fatty acids (For example oleic acid)

Discussion

  • Oleoyl CoA undergoes three cycles of β-oxidation like normal saturated fatty acids to yield 3 molecules of acetyl CoA and results in the formation of 12-carbon fatty acyl-CoA with a cis double bond now between carbon 3 and 4. This product is known as cis-Δ3-Dodecenoyl-CoA.
  • The above product formed has a cis double bond and cannot further participate in β-oxidation. Thus by the action of Δ32-enoyl-CoA isomerase, cis-Δ3-Dodecenoyl-CoA is converted to trans-Δ2-Dodecenoyl-CoA. This is the significance of the isomerase enzyme in the β-oxidation of unsaturated fatty acids.
  • trans-Δ2-Dodecenoyl-CoA now is acted upon by the enzymes of β-oxidation pathway in five continuous cycles to yield another 6 molecules of acetyl CoA.
  • The acetyl-CoA molecules now enter the Kreb’s cycle.

β-Oxidation of Polyunsaturated Fatty Acid

Oxidation of polyunsaturated fatty acids

Oxidation of polyunsaturated fatty acids

Discussion

  • Linolenic acid is an unsaturated fatty acid with two cis double bonds. Like saturated fatty acids the polysaturated fatty acid undergoes three cycles of β-oxidation to yield three molecules of acetyl CoA along with a 12 carbon chain fatty acyl-CoA with cis double bonds at position 3 and 6 (cis-Δ3,cis-Δ6).
  • Since the mitochondrial enzymes cannot break down cis double bonds, Δ32-enoyl-CoA isomerase converts it to (trans-Δ2,cis-Δ6) fatty acyl-CoA. The latter product now undergoes one more cycle of β-oxidation to yield the fourth molecule of acetyl CoA and the remaining product left behind is cis-Δ4 fatty acyl-CoA.
  • By the action of acyl-CoA dehydrogenase, the first step of β-oxidation is achieved, resulting in formation of a double bond at position 2 forming the product (trans-Δ2,cis-Δ4) fatty acyl-CoA. The newly formed product is now acted upon by the enzyme 2,4-dienoyl CoA-reductase to form trans-Δ3 fatty acyl-CoA which on further action by enoyl-CoA isomerase gives trans-Δ2 fatty acyl-CoA.
  • trans-Δ2 fatty acyl CoA now undergoes four cycles of β-oxidation to yield another five molecules of acetyl CoA.
  • The acetyl-CoA molecules now enter the Kreb’s cycle.

Recommended Texts

  1. David L. Nelson and Michael M. Cox, Lehninger Principles of Biochemistry 6th Edition
  2. Jeremy M. Berg, John L. Tymockzo and Luber Stryer, Biochemistry 7th Edition
  3. Reginald H. Garrett, Charles M. Grisham, Biochemistry by Reginald H Garrett 5th Edition.
  4. U. Satyanarayana, U. Chakrapani, Biochemistry by U. Satyanarayana. 3rd Edition.

About Sweety Mehta

Studied B. Pharm. at Mumbai Educational Trust Institute of Pharmacy (Mumbai). Worked at Cipla, Mumbai as Marketing executive for 2 years and 9 months. Earned a diploma in marketing from Welingkar's Institute of Management Development and Research.