Methylmalonyl Coenzyme A mutase

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Methylmalonyl Coenzyme A mutase
Identifiers
Symbol	MUT
HUGO	7526
Entrez	4594
OMIM	251000
RefSeq	NM_000255
UniProt	P22033
Other data
EC number	5.4.99.2
Locus	Chr. 6 p21

MUT is an enzyme that converts MMl-CoA into Succinyl-CoA (Su-CoA). MUT is specific for (R)-MMl-CoA. The enzyme, which catalyzes an unusual carbon skeleton rearrangement, utilizes AdoB₁₂ as a coenzyme.

[edit] Structure

[edit] Function

MUT resides in the mitochondria where a number of substances, including the branched-chain amino acids Ile and Val, as well as Met, Thr, thymine and odd-chain FAs are metabolized via Methylmalonate semialdehyde (MMlSA) or Propionyl-CoA (Pr-CoA) to a common compound - Methyl-malonyl-CoA (MMl-CoA).

MUT reaction mechanism begins with homolytic cleavage of AdoB12's C-Co(III) bond, the C and Co atoms each acquire one of the electrons that formed the cleaved electron pair bond. The Co ion therefore fluctuates between its Co(III) and Co(II) oxidation states [the two states are spectroscopically distinguishable: Co(III) is red and diamagnetic (no unpaired electrons), whereas Co(II) is yellow and paramagnetic (unpaired electrons)]. Hence, the role of coenzyme B₁₂ in the catalytic process is that of a reversible free radical generator. The C-Co(III) bond is well suited to this function because it is inherently weak (dissociation energy = 109 kJ/mol) and appears to be further weakened through steric interactions with the enzyme. A homolytic cleavage reaction is unusual in biology; most other biological bond cleavage reactions occur via heterolytic cleavage (in which the electron pair forming the cleaved bond is fully acquired by one of the separating atoms). [2](p.)