CHEM 445 / BIOL 445
Biochemistry II

J. D. Cronk
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20. header

Lecture 20. Fatty acid metabolism: Special problems

Wednesday 7 March 2007

The thiolase mechanism - a Claisen ester cleavage. Special problems in fatty acid oxidation: double bonds and odd chains. Vitamin B12 and the mechanism of methylmalonyl CoA mutase. Peroxisomal oxidation of fatty acids.

Reading: BTS6, Ch.22, pp.626-630.

  
20. Summary

Lecture 20 Summary

Special problems in fatty acid degradation

The cycle of reactions constituting b-oxidation of fatty acids only metabolizes saturated regions of the fatty acid chain. When a double bond of an unsaturated fatty acid is encountered, an alternate set of reactions and their enzymes processes that part of the chain. The alternate pathway, reminiscent of a subroutine in a computer program, deals with an example of what I like to call a "special problem" in metabolism.

Diagram of metabolism of unsaturated fatty acids (thumbnail)   Since b-oxidation operates in two-carbon steps, another special problem arises when a fatty acid with an odd number of carbon atoms is processed. Such "odd chain" fatty acids yield propionyl CoA as the end product of b-oxidation. Propionyl CoA is tranformed into succinyl CoA by a series of three steps, catalyzed by the following enzymes: (1) Propionyl CoA carboxylase [EC 6.4.1.3], a biotin-dependent carboxylase, (2) Methylmalonyl CoA epimerase [EC 5.1.99.1]. (3) Methylmalonyl CoA mutase [EC 5.4.99.2], an unusual and fascinating enzyme that catalyzes a rearrangement reaction via a radical intermediate. The prosthetic group of the enzyme, 5'-deoxyadenosylcobalamin, is derived from vitamin-B12.   Diagram of metabolism of odd chain fatty acids (thumbnail)
unsaturated fatty acid odd chain fatty acids

Peroxisomal oxidation of fatty acids

In oxidation of fatty acids in peroxisomes, the first oxidation step leads (more directly) to reduction of oxygen (via flavoprotein and catalase, which is carried out by a peroxisomal acyl CoA oxidase [EC 1.3.3.6].

Study questions

  • Describe the chemical property of 5'-deoxyadenosylcobalamin that makes possible the radical mechanism of methylmalonyl CoA mutase, and the effect of protein structure on the cofactor.
  • Name three biotin-dependent carboxylases, and describe their biochemical activities and metabolic roles.

Page updated 12-27-06

References

1. Berg, Tymoczko, and Stryer. Biochemistry (BTS): 6th edition (2007, Freeman) Ch.22, pp.626-630.
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