Ribonucleotide reductase cobalamin dependent

Three types of enzymatic reactions depend upon alkyl corrin coenzymes. The first is the reduction of ribonucleotide triphosphates by cobalamin-dependent ribonucleotide reductase, a process involving intermo-lecular hydrogen transfer (Eq. 16-21). The second type of reaction encompasses the series of isomerizations shown in Table 16-1. These can all be depicted as in Eq. 16-34. Some group X, which may be attached by a C-C, C-O, or C-N bond, is transferred to an adjacent carbon atom bearing a hydrogen. At the same time,... 

Vitamin B12 coenzyme 864. See also Cobalamin dependent reactions, table 871 enzymatic functions 870 - 877 isomerization reactions 872 nonenzymatic cleavage 870 ribonucleotide reductase 871 Vitamin B6 family 721, 738... 

Numerous analogs of adenosylcobalamin have been tested for their ability to replace or to inhibit the action of the coenzyme in the adenosyl-cobalamin-dependent ribonucleotide reductase reaction the enzyme from L. leichmannii has been used in most of these studies. Kinetic studies have been used in most investigations of analog-enzyme interactions and thus the interpretation of data regarding the affinity of analogs for the reductase is subject to the limitations imposed on kinetic studies of a complex reaction. 

All non-heme iron containing ribonucleotide reductases are also inhibited by hydroxyurea and related hydroxamates, while the adenosyl-cobalamin-dependent reductases are not affected (27, 156). The inhibition by these reagents can be partially reversed by excess Fe+2 or dithiols. Reaction of ribonucleotide reductase of E. coli with [14C]hydro-xyurea inactivated only the B2 subunit and this inactivation was not reversed by removal of the radioactivity (157). Inactivation by hydroxyurea does not affect the iron content of protein B2, but involves the destruction of the stable free radical (66,67). Reactivation can be accomplished by removal of the iron and reconstitution of apoprotein B2 with Fe+2. Hydroxyurea has been demonstrated to be a powerful radical scavenger in another system (158). 

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