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Reaction Mechanism

Further insight into the reaction mechanism was gathered by Frey, who found that SAM plays a similar role to adenosylcobalamin for generation of radicals, rec ognized by proving the existence of a 5 '-deoxyadenosyl radical as intermediate. Because SAM is a much simpler molecule than cobalamin, Frey refers to SAM as ''a poor man's adenosylcobalamin'' [33, 34]. To confirm the role of SAM, non-stereospecifically labeled [5'-3H]SAM was applied to the incubation mixture [35]. The tritium label was found to be completely transferred to the substrate and the product indicating that the 5 '-deoxyadenosyl moiety 31 is cleaved from SAM. The resulting active species 31 should be involved in the transfer of the pro-3R hydrogen of a-lysine 24 to the pro-2R position in ¡-lysine 25. Frey [36] suggests that the reaction proceeds after cleavage of SAM and generation of the 5' -deoxyadenosyl radical 31 by abstraction of the pro-3R hydrogen from a-lysine bound as aldimine 26 to PLP. In the next step the a-lysyl radical 27 is isomerized to the ¡-lysyl radical 29. Abstraction of a hydrogen from the methyl group of 5'-deoxyadenosine generates a ¡-lysyl aldimine 30, that is finally hydrolyzed to ¡-lysine (Scheme 1.6.7). This reaction sequence implies regeneration of the 5 '-deoxyadenosyl radical.

Mo CH2 U C02H

Mo CH2 U C02H

OPO,

OPO,

(S)-lysine 2,3-aminomutase

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