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CASE FILES: BIOCHEMISTRY
Role of cobalamin in metabolism:
Cobalamin plays a vital role in the catab-
olism of odd-chain fatty acids, threonine, methionine, and the branched-chain
amino acids (leucine, isoleucine, and valine) as shown in Figure 42-4. The
degradation of each of the compounds named above produces the same
metabolite, propionyl-CoA. This activated three-carbon fatty acid enters the
energy generating metabolic pathway at the level of the citric acid cycle as
succinyl-CoA. The process requires three specialized enzymes. Propionyl-
CoA carboxylase adds another carbon to propionyl-CoA to form D-
methylmalonyl-CoA in a reaction which requires ATP and the CO2-binding
cofactor biotin. A racemase converts the D isomer of methylmalonyl-CoA to
the L isomer. The last step is catalyzed by methylmalonyl-CoA mutase, a
deoxyadenosylcobalamin requiring enzyme that moves the acyl-CoA group
from the methylene carbon to the methyl carbon to form succinyl-CoA. In
cases of cobalamin deficiency this reaction is compromised and leads to an
accumulation of methylmalonyl-CoA in serum, which has been suggested as a
possible source of neurologic defects seen in cobalamin deficiency by decreas-
ing lipid synthesis. On the other hand, impaired biosynthesis of phosphatidyl
choline due to decreased levels of methionine and S-adenosylmethionine
(SAM) may play a role for the neurologic symptoms of cobalamin deficiency
by compromising the repair of demyelination.
SCoA
methionine
SCoA
SCoA
isoleucine
ATP
ADP + P
C = 0
C = 0
valine
HC-COO
propionyl CoA
carboxylase
threonine
(biotin)
propionyl CoA
D-methylmalonyl CoA
odd-chain fatty acids
methylmalonyl CoA
racemase
SCoA
methylmalonyl CoA
C = 0
mutase
h2c -
ch2
(vitB12)
COO
succinyl CoA
L-methylmalonyl CoA
Figure 42-4. The role of vitamin B12 in the conversion of propionyl-CoA to
succinyl-CoA.
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