Odd++Number+Fatty+Oxidation

=Odd Number Fatty Acid Oxidation=

Authors: Ashley DeYoung, Taylor Robinson, and Amanda Young

=Introduction=

Fatty acids with an odd number of carbons are rare in mammals, but common in plants and marine organisms. Therefore, humans and animals that include these things in their diets metabolize them via the β-oxidation pathway. This particular step in the pathway uses propionyl-CoA,which has three carbons, instead of acetyl-CoA. There are three reactions that lead to the conversion of propionyl-CoA to succinyl-CoA in order to enter the TCA cycle [1][2]. Cofactors ||= Reaction Type ||= Products || **Carboxylation of Propionyl-CoA Yields D-Methylmalonyl-CoA**
 * = #  ||= Substrates ||= Enzymes ||= Coenzymes/
 * = 1 ||= Propionyl-CoA, Carbon Dioxide, Water ||= Propionyl-CoA carboxylase ||= ATP, biotin ||= Carboxylation ||= D-methylmalonyl-CoA ||
 * = 2 ||= D-methylmalonyl-CoA ||= Methylmalonyl-CoA epimerase ||= None ||= Isomerization ||= L-methylmalonyl-CoA ||
 * = 3 ||= L-methylmalonyl-CoA ||= Methylmalonyl-CoA mutase ||= Vitamin B12 Complex ||= Isomerization ||= Succinyl-CoA ||

The first step uses propionyl-CoA carboxylase to carboxylate the α-carbon of propionyl-CoA to produce D-methylmalonyl-CoA. The mechanism involves ATP-driven carboxylation of biotin at N-1 followed by nucleophilic attack by the α-carbanion of propionyl-CoA in a stereospecific manner. =Isomerization of D-Methylmalonyl-CoA Producing L-Methylmalonyl-CoA=

D-methylmalonyl-CoA is converted to the L isomer by methylmalonyl-CoA epimerase. The epimerase reaction involves a carbanion at the α-position formed via a reversible dissociation of the acidic α-proton (Figure 2). This reaction is important because the L isomer is a substrate for methylmalonyl-CoA mutase, which is the enzyme used to catalyze the third reaction. Methylmalonyl-CoA epimerase enhances the reaction rate by a factor of 10E14. =Methylmalonyl-CoA Mutase Rearranges L-Methylmalonyl-CoA to Succinyl-CoA=

This last reaction is peculiar in that it moves the carbonyl-CoA group from one carbon to its neighbor. This rearrangement involves a radical mechanism, which is induced by 5-deoxyadenosine cobalmin coenzyme complex (vitamin B12). Cobalt transforms between the Cobalt(III) fully bonded ligand and the Cobalt(II) loosely complexed radical. The radical can capture a hydrogen free radical from the substrate by one electron transfer. This radical form of the substrate then rearranges through a cyclopropaniod intermediate ending with a recapture of the hydrogen free radical back from the coenzyme. **Outcomes of Disruption in Odd Number Fatty Acid Oxidation**

Disruption in the fatty acid β-oxidation of odd numbered carbons can be caused by propionyl-CoA carboxylase deficiency, defects in biotin transport or metabolism, methylmalonyl-CoA mutase deficiency, or lastly adenosylcobalamin synthesis. The first two defects result in propionic acidemia and the last two, methylmalonic acidemia. The development of either of these causes metabolic acidosis, a condition in which the body produces too much acid or the kidney is not removing enough acid from the body. These genetic disorders cause the pH to be lowered below 7.35 resulting in coma or death [3]. =References=

1. //Fatty Acid Catabolism//, http://web.virginia.edu/heidi/chapter24/chp24frameset.htm.* 2. Garrett, R.H., & Grisham, C.M. (2010). //Biochemistry//. Boston, MA: Brooks/Cole. 3. Bhagavan, N.V. (2002). //Medical Biochemistry//. San Diego, CA: Harcourt Academic Press.


 * All figures referenced here.