Methylglyoxal detoxification by E. coli aldo-keto reductase = 대장균 aldo-keto reductase에 의한 methylglyoxal 해독작용

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Methyglyoxal is a toxic metabolite known to accumulate in various cell types. We detected in vivo conversion of methylglyoxal (MG) to acetol in MG-accumulating Escherichia coli cells by $^1H-NMR$ spectroscopy. Search for homologs of the mammalian aldo-keto reductases, reported to exhibit activity to MG, revealed nine open-reading frames from the E. coli genome. Based on both sequence similarities and preliminary screening with $^1H-NMR$ for crude proteins of the corresponding mutant strains, we selected five genes, yafB, yqhE, yeaE, yghZ, and yajO, for further study. Quantitative assessment of acetol production including its metabolite 1,2-propanediol from the crude extracts of these mutants indicated that the yafB, yqhE, and yghZ genes are significantly involved in the metabolic conversion of MG in the presence of NADPH. Enzymatic properties of these proteins with the Km values of 2.1 - 6.9 mM are consistent with the in vivo and cell-free activities of MG conversion. Substrate specificities of these enzymes toward various aldehydes and ketones demonstrate their similarities to the mammalian aldo-keto reductases. The results imply that the glutathione-independent detoxification of MG can occur through multiple pathways of aldo-keto reductases, leading to a generation of acetol.
Advisors
Park, Chan-Kyuresearcher박찬규researcher
Description
한국과학기술원 : 생명과학과,
Publisher
한국과학기술원
Issue Date
2005
Identifier
244504/325007  / 000955008
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 생명과학과, 2005.2, [ vi, 118 p. ]

Keywords

aldo-keto reductase; methylglyoxal; acetol; 아세톨; 알도케토환원효소; 메칠글리옥살

URI
http://hdl.handle.net/10203/27584
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=244504&flag=dissertation
Appears in Collection
BS-Theses_Ph.D.(박사논문)
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