Adenosylcobalamin-dependent enzymes

2-rearrangement of a substrate molecule is now recognized as a common feature of several bacterial fermentation pathways. In general, the rearrangement enables the substrate to be readily assimilated into 

FIGURE 4. The eleven adenosylcobalamin-dependent rearrangements so far described. Notes D-a-lysine [L-p-lysine] 5,6-aminomutase catalyzes similar rearrangements on two substrates diol dehydrase and glycerol dehydrase have over-lapping substrate specificity. 

A shortcoming of this mechanism is that it provides no explicit role for the protein, nor does it address the issue of how the substrate and product radicals interconvert (this is discussed in more detail in Section 3.2). Later on (Section 3.1) we shall see that even the participation of AdoCH2 in 

FIGURE 5. A minimal scheme for the mechanism of AdoCbl-dependent rearrangements. Adapted from Halpem (1985). 

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Coordination Compounds in Biology Table 19 Adenosylcobalamin-dependent Enzymes... 

Interaction with Adenosylcobalamin. It has been considered generally that adenosylcobalamin or its analogs binds to the apoprotein of diol dehydrase or other adenosylcobalamin-dependent enzymes almost irreversibly (4). However, we found that the holo-enzyme of diol dehydrase was resolved completely into intact apoen-zyme and adenosylcobalamin when subjected to gel filtration on a Sephadex G-25 column in the absence of K+ (9, 10). Among the inactive complexes of diol dehydrase with irreversible cobalamin inhibitors, those with cyanocobalamin and methylcobalamin also were resolved upon gel filtration on Sephadex G-25 in the absence of both K+ and substrate, yielding the apoenzyme, which was reconstitutable into the active holoenzyme (II). The enzyme-hydroxocobalamin complex, however, was not resolvable under the same conditions. The enzyme-cobalamin complexes were not resolved at all by gel filtration in the presence of both K+ and substrate. When gel filtration of the holoenzyme was carried out in the presence of K+ only, the holoen-... 

FIGURE 1. The general rearrangement catalyzed by adenosylcobalamin-dependent enzymes. 

Chemaly, S. M., 1994, a-Methyleneglutarate mutase an adenosylcobalamin-dependent enzyme, S. Afr. J. Chem. 47 37947. 

Golding, B. T., and Rao, D. N. R., 1986, Adenosylcobalamin-dependent enzymic reactions. In Enzyme Mechanisms (M. L. Page and A. Williams, eds.), London Royal Society of Chemistry, pp. 404n428. 

Tobimatsu, T., Sakai, T., Hashida, Y., Mizoguchi, N., Miyoshi, S., and Toraya, T., 1997, Heterologous expression, purification, and properties of diol dehydratase, an adenosylcobalamin-dependent enzyme of Klebsiella oxytoca, Arch. Biochem. Biophys. 347 1320140. 

This step is the culmination of a reaction sequence in which propionyl-CoA, a toxic metabolite derived from the degradation of fats, is removed from circulation. Carboxylation of propionyl-CoA gives (5)-methylmalonyl-CoA, which is epimerized to (/ )-methylmalonyl-CoA. Conversion of the (7 )-isomer to succinyl-CoA allows further metabolism via the Krebs cycle [74]. Methylmalonyl-CoA mutase is also the only adenosylcobalamin-dependent enzyme known to participate in human metabolism, and as such has received significant study [30, 37, 38]. 

Reed, G. H. (2004). Radical mechanisms in adenosylcobalamin-dependent enzymes. Current Opinion in Chemical Biology, 8, 477—483. 

Homolytic scission of the Co—C5 bond in adenosylcobalamin is brought about thermally at high temperatures (>80 °C), by photolysis, or by the actions of adenosylcobalamin-dependent enzymes. The fate of the 5 -deoxyadenosyl radical depends on the reaction conditions. In an enzymatic site, the radical most often abstracts a hydrogen atom from a substrate to initiate a radical rearrangement process in the substrate. In the absence of a substrate or/and enzyme, the 5 -deoxyadenosyl radical faces alternative fates. In anoxic conditions, photolysis of adenosylcobalamin to the transient 5 -deoxyadenosyl radical ends in cyclization to 5, 8-cyclo-adenosine, as shown in Figure 5, in what must be a multistep process." In the presence of oxygen gas, the 5 -deoxyadenosyl radical reacts with oxygen to form adenosine-5 -aldehyde. ... 

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