Oxidation of Lipids IV

Suaib Luqman

epgp books

 

  1. Objectives
  • v To understand the unsaturated fatty acid oxidation
  • v α and ώ-oxidation
  • v How fatty acid oxidation takes place in peroxisomes
  1. Concept Map
  1. Description

 

Unsaturated Fatty Acid Oxidation

 

 

For unsturated fatty acid degradation, two additional steps are required along with the other reactions of β-oxidation catalyzed by enzymes: an isomerase and a reductase. Monounsaturated fatty acid require only isomerase while polyunsaturated fatty acid requires both isomerase and reductase.

 

Problem with Monounsaturated Fatty Acid

 

For example: Degradation of Palmitoleate (C16 unsaturated fatty acid having double bond between C-9 and C-10).

 

  1. Activation and transportation occurs similarly as that of saturated fatty acid i.e. across inner mitochondrial membrane
  2. The first two reactions are same while the third reaction does not occur as cis– 3-enoyl CoA is formedinstead of trans 2-enoyl CoA, therefore the enzyme which is not specific  as given in figure

The configuration of double bond between C2 and C3 is prevented by already present double bond amid C3 and C4. This problem is solved by shifting the arrangement and configuration of the cis– 3-double bond into trans

 

2 double bond by isomerase enzyme.

 

Problem with Polyunsaturated Fatty Acid

 

 

For example linoleate, C18 polyunsaturated fatty acids with cis ∆9 and cis ∆12 double bonds. The cis ∆3 double bond created after completion of three cycles of the β-oxidation is transformed by isomerise to a trans ∆2 double bond. But another round of cycle results into a cis ∆4 double bond and its dehydrogenation yields a 2,4-dienoyl intermediate by Acyl CoA dehydrogenase. This intermediary product is not the substrate for the subsequent enzyme in the β-oxidation conduit. However, the deadlock is overcome by diminution of this intermediary product to trans ∆3-enoyl CoA by NADPH-dependent 2,4-dienoyl CoA reductase enzyme. The product trans ∆3-enoyl CoA is converted to trans ∆2 form by cis ∆3-enoyl CoA isomerase. The remaining steps are same.

 

Relatively unimportant pathway for the production of energy and are mainly used when dietary fatty acids are branched, odd chain and are methylated. Plants contain phytol and are present as one of the constituent of chlorophyll (the long hydrocarbon side-chain) and its metabolite known as Phytanic acid is metabolized by α-oxidation. This phytanic acid is present in milk lipid, food derived from milk and animal fat and is metabolized by preliminary α-hydroxylation trailing by dehydrogenation and decarboxylation. The phytanic acid holds a methyl group attached to the β-carbon suggesting the fact that the composite is not a substrate for β-oxidation. Hence, phytanic acid should be obliged to undergo α-oxidation. This pathway is also operative in brain and plant tissues.

 

 

Due to the deficiency of phytate α- hydroxylase, a neurological problems occurs known as Refsam`s disease (inborn error of metabolism) which phytanic acid is not metabolized and it accumulates in blood and tissues.

 

 

The most important features of α oxidation are as under:

 

  1. Merely long chain free fatty acids serve as substrates.
  2. Indirect involvement of molecular oxygen.
  3. CoA intermediates are not required.
  4. It does not show the way to generate high energy phosphates.

ω-Oxidation

 

 

A minor pathway in which ω terminus carbon is oxidized to carboxyl group to form dicarboxylic acids. Further metabolism take place by β-oxidation.

Verkade and his group was the first to report the biological oxidation of fatty acid at the omega (ω) carbon atom. His group isolated dicarboxylic acids of the equivalent chain length from the urine as those that were fed in the form of TAGs. He also projected that a variety of acids were first oxidized at the ω carbon atom and subsequently metabolized by β-oxidation ensuing from the both ends of dicarboxylic acid.

The mechanism involves an initial hydroxylation of the methyl group present at the terminal position of a primary alcohol. In animals, the hydroxylase from the cytochrome P450 system is conscientious for the alkane hydroxylation; whereas in bacteria, rubridoxin is the transitional electron carrier that feeds electrons to ω hydroxylase system. The instantaneous product, RCH2OH is oxidized to an aldehyde by an Alcohol dehydrogenase, which in turn is decomposed to a carboxylic acid by an Aldehyde dehydrogenase in both animal and microbial systems. Rapidly, the -CH3 group is transformed to a -CH2OH group which subsequently is oxidized to -COOH, consequently producing a dicarboxylic acid. The so formed dicarboxylic acid may be reduced from either part of the molecule by the β-oxidation chain to figure out Acetyl CoA.

 

These reaction sequences now have implicit an enormously vital scavenging function in the bacterial biodegradation of both detergents resultant from fatty acids and still more imperative the huge amounts of oil spilled over the ocean surface. The pace of bacterial decomposition of floating oil underneath aerobic conditions is estimated as high as 0.5g/day per square metre of the oil surface. The bacterial decomposition of the oils is brought about principally by ω oxidation method.

 

Oxidation of Fatty Acids in Peroxisomes

 

 

Maximum fatty acid oxidation takes place in mitochondria, few oxidations occur in cellular peroxisomes. Peroxisomes are having high concentrations of catalase. It is important for the oxidation of octanyl CoA and it helps in shortening long chains for making better substrates of beta oxidation in mitochondria. Flavoprotein dehydrogenase present in peroxisomes transfers electrons to oxygen to yield hydrogen peroxide as a replacement for incarcerating the electrons as FADH2 as crop up in mitochondrial β-oxidation. The conditions in which functional peroxisomes are absent are known as Zellweger syndrome in which death occurs by age six.

 

What Triggers the Switch towards Fatty Acid Oxidation?

 

During fasting, the ratio of insulin: glucagon is low resulting in the stimulation of lipolysis. The overall of fasting or stress leading to opposite regulation of insulin is the switch from a fuel economy based on carbohydrate in which major proportion of energy comes from lipid oxidation.

 

 

  1. Summary

 

In this lecture we learnt about:

 

  • The α and ώ-oxidation
  • The oxidation of fatty acid in peroxisomes
  • What Triggers the Switch towards Oxidation of Fatty Acid
you can view video on Oxidation of Lipids IV

 

 

Weblinks

 

 

 

Books

 

  1. Lehninger Principles of Biochemistry by David L. Nelson, Albert‎ L. Lehninger, Michael‎ M. Cox. 2008. https://books.google.co.in/books?isbn=071677108X
  2. Patti A.; Eaton Simon, eds. (1999), Current views of fatty acid oxidation and ketogenesis : from organelles to point mutations 466 (2nd ed.), New York, NY: Kluwer Acad./Plenum Publ., pp. 292–295, ISBN 0-306-46200-1
  1. Textbook Of Biochemistry And Human Biology by G. P. TALWAR, L‎ .M. SRIVASTAVA. 2002. Page 372. https://books.google.co.in/books?isbn=8120319656
  2. The Alpha-oxidation of Long-chain Fatty Acids by Higher Plants by Robert Oren Martin. 1959. https://books.google.co.in/books?id=rLhKAQAAMAAJ
  3. A Balanced Omega-6/Omega-3 Fatty Acid Ratio, Cholesterol … by A.P. Simopoulos, F‎. De Meester – 2009. https://books.google.co.in/books?isbn=3805592256
  4. Omega 3 Fatty Acid Research by M. C. Teale. 2006. Page 110 https://books.google.co.in/books?isbn=1594546207