[Microbe-inspired system enzymology of vitamin B₁₂ metabolism].

نویسنده

  • Tetsuo Toraya
چکیده

Vitamin B₁₂ is produced only by prokaryotes and utilized by animals as an essential micronutrient. Genetic complementation analysis of cell lines from patients indicated that at least eight gene products are involved in intracellular B₁₂ metabolism and utilization. We have investigated bacterial adenosylcobalamin-dependent enzymes and elucidated their structure-based fine mechanisms. They tend to undergo mechanism-based inactivation during catalysis, because they use highly reactive radicals for catalyzing chemically difficult reactions. We have discovered molecular chaperone-like reactivating factors for these enzymes that release a damaged cofactor forming apoenzyme. Methylcobalamin-dependent methionine synthase also undergoes inactivation, because it utilizes cob (I) alamin, a super nucleophile, for catalysis. Methionine synthase reductase is a reactivating partner for this enzyme. Recent studies suggested that activity-maintaining systems for B₁₂ enzymes are present in animal cells as well, and thus hints for designing therapeutic agents for B₁₂-related metabolic disorders might be obtained from the investigations of microbial B₁₂ metabolism.

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عنوان ژورنال:
  • Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan

دوره 130 11  شماره 

صفحات  -

تاریخ انتشار 2010