Lysine 2,3-aminomutase. Support for a mechanism of hydrogen transfer involving S-adenosylmethionine.
The conversion of L-lysine to L-beta-lysine is catalyzed by lysine 2,3-aminomutase. The reaction involves the interchange of the 2-amino group of lysine with a hydrogen at carbon 3. As such the reaction is formally analogous to adenosylcobalamin-dependent rearrangements. However, the enzyme does not contain and is not activated by this coenzyme. Instead it contains iron and pyridoxal phosphate and is activated by S-adenosylmethionine. Earlier experiments implicated adenosyl-C-5' of S-adenosylmethionine in the hydrogen transfer mechanism, apparently in a role similar or analogous to that of adenosyl moiety of adenosylcobalamin in the B12-dependent rearrangements. The question of whether both hydrogens or only one hydrogen at adenosyl-C-5' participate in the hydrogen-transfer process has been addressed by carrying out the lysine 2,3-aminomutase reaction with S-[5'-3H] adenosylmethionine in the presence of 10 times its molar concentration of enzyme. Under these conditions all of the tritium appeared in lysine and beta-lysine, showing that C-5'-hydrogens participate. To determine whether hydrogen transfer is compulsorily intermolecular and intramolecular, various molar ratios of [3,3-2H2]lysine and unlabeled lysine were submitted to the action of lysine 2,3-aminomutase under conditions in which 10-15% conversion to beta-lysine occurred. Mass spectral analysis of the beta-lysine for monodeutero and dideutero species showed conclusively that hydrogen transfer is both intramolecular and intermolecular. The results quantitatively support our postulate that activation of the enzyme involves a transformation of S-adenosylmethionine into a form that promotes the generation of an adenosyl-5' free radical, which abstracts hydrogen from lysine to form 5'-deoxyadenosine as an intermediate.
Baraniak
J
J
Institute for Enzyme Research, Graduate School, University of Wisconsin-Madison 53705.
Moss
M L
ML
Frey
P A
PA
D000591:Amino Acid Isomerases / Q000378:metabolism*; D006859:Hydrogen / Q000378:metabolism; D019751:Intramolecular Transferases; D008239:Lysine / Q000378:metabolism / Q000031:analogs & derivatives; D008956:Models, Chemical; D012436:S-Adenosylmethionine / Q000378:metabolism*
C065591:beta-lysine; D012436:S-Adenosylmethionine; D006859:Hydrogen; D000591:Amino Acid Isomerases; D019751:Intramolecular Transferases; C021518:lysine 2,3-aminomutase; D008239:Lysine