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Inhibition effects of furfural on alcohol dehydrogenase, aldehyde dehydrogenase and pyruvate dehydrogenase.

Modig, Tobias LU ; Lidén, Gunnar LU and Taherzadeh, Mohammad J (2002) In Biochemical Journal 363(Pt 3). p.769-776
Abstract
The kinetics of furfural inhibition of the enzymes alcohol dehydrogenase (ADH; EC 1.1.1.1), aldehyde dehydrogenase (AlDH; EC 1.2.1.5) and the pyruvate dehydrogenase (PDH) complex were studied in vitro. At a concentration of less than 2 mM furfural was found to decrease the activity of both PDH and AlDH by more than 90%, whereas the ADH activity decreased by less than 20% at the same concentration. Furfural inhibition of ADH and AlDH activities could be described well by a competitive inhibition model, whereas the inhibition of PDH was best described as non-competitive. The estimated K(m) value of AlDH for furfural was found to be about 5 microM, which was lower than that for acetaldehyde (10 microM). For ADH, however, the estimated K(m)... (More)
The kinetics of furfural inhibition of the enzymes alcohol dehydrogenase (ADH; EC 1.1.1.1), aldehyde dehydrogenase (AlDH; EC 1.2.1.5) and the pyruvate dehydrogenase (PDH) complex were studied in vitro. At a concentration of less than 2 mM furfural was found to decrease the activity of both PDH and AlDH by more than 90%, whereas the ADH activity decreased by less than 20% at the same concentration. Furfural inhibition of ADH and AlDH activities could be described well by a competitive inhibition model, whereas the inhibition of PDH was best described as non-competitive. The estimated K(m) value of AlDH for furfural was found to be about 5 microM, which was lower than that for acetaldehyde (10 microM). For ADH, however, the estimated K(m) value for furfural (1.2 mM) was higher than that for acetaldehyde (0.4 mM). The inhibition of the three enzymes by 5-hydroxymethylfurfural (HMF) was also measured. The inhibition caused by HMF of ADH was very similar to that caused by furfural. However, HMF did not inhibit either AlDH or PDH as severely as furfural. The inhibition effects on the three enzymes could well explain previously reported in vivo effects caused by furfural and HMF on the overall metabolism of Saccharomyces cerevisiae, suggesting a critical role of these enzymes in the observed inhibition. (Less)
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keywords
Binding, Competitive, Furaldehyde : pharmacology, Furaldehyde : analogs & derivatives, Models, Kinetics, Chemical, Pyruvate Dehydrogenase Complex : antagonists & inhibitors, Pyruvate Dehydrogenase Complex : metabolism, Pyruvic Acid : metabolism, Saccharomyces cerevisiae : enzymology, Aldehyde Dehydrogenase : antagonists & inhibitors, Alcohol Dehydrogenase : antagonists & inhibitors
in
Biochemical Journal
volume
363
issue
Pt 3
pages
769 - 776
publisher
Portland Press Limited
external identifiers
  • pmid:11964178
  • wos:000175651600037
  • scopus:0036566476
ISSN
0264-6021
language
English
LU publication?
yes
id
62188f5e-d8ae-4af2-947e-3608717a6fed (old id 107747)
alternative location
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11964178&dopt=Abstract
date added to LUP
2007-06-25 13:29:20
date last changed
2017-12-10 04:37:26
@article{62188f5e-d8ae-4af2-947e-3608717a6fed,
  abstract     = {The kinetics of furfural inhibition of the enzymes alcohol dehydrogenase (ADH; EC 1.1.1.1), aldehyde dehydrogenase (AlDH; EC 1.2.1.5) and the pyruvate dehydrogenase (PDH) complex were studied in vitro. At a concentration of less than 2 mM furfural was found to decrease the activity of both PDH and AlDH by more than 90%, whereas the ADH activity decreased by less than 20% at the same concentration. Furfural inhibition of ADH and AlDH activities could be described well by a competitive inhibition model, whereas the inhibition of PDH was best described as non-competitive. The estimated K(m) value of AlDH for furfural was found to be about 5 microM, which was lower than that for acetaldehyde (10 microM). For ADH, however, the estimated K(m) value for furfural (1.2 mM) was higher than that for acetaldehyde (0.4 mM). The inhibition of the three enzymes by 5-hydroxymethylfurfural (HMF) was also measured. The inhibition caused by HMF of ADH was very similar to that caused by furfural. However, HMF did not inhibit either AlDH or PDH as severely as furfural. The inhibition effects on the three enzymes could well explain previously reported in vivo effects caused by furfural and HMF on the overall metabolism of Saccharomyces cerevisiae, suggesting a critical role of these enzymes in the observed inhibition.},
  author       = {Modig, Tobias and Lidén, Gunnar and Taherzadeh, Mohammad J},
  issn         = {0264-6021},
  keyword      = {Binding,Competitive,Furaldehyde : pharmacology,Furaldehyde : analogs & derivatives,Models,Kinetics,Chemical,Pyruvate Dehydrogenase Complex : antagonists & inhibitors,Pyruvate Dehydrogenase Complex : metabolism,Pyruvic Acid : metabolism,Saccharomyces cerevisiae : enzymology,Aldehyde Dehydrogenase : antagonists & inhibitors,Alcohol Dehydrogenase : antagonists & inhibitors},
  language     = {eng},
  number       = {Pt 3},
  pages        = {769--776},
  publisher    = {Portland Press Limited},
  series       = {Biochemical Journal},
  title        = {Inhibition effects of furfural on alcohol dehydrogenase, aldehyde dehydrogenase and pyruvate dehydrogenase.},
  volume       = {363},
  year         = {2002},
}