Inhibition effects of furfural on alcohol dehydrogenase, aldehyde dehydrogenase and pyruvate dehydrogenase.
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.
Modig
Tobias
T
Department of Chemical Engineering II, Lund University, P.O. Box 124, SE-22100, Lund, Sweden.
Lidén
Gunnar
G
Taherzadeh
Mohammad J
MJ
D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors*; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors*; D001667:Binding, Competitive; D005662:Furaldehyde / Q000031:analogs & derivatives* / Q000494:pharmacology*; D007700:Kinetics; D008956:Models, Chemical; D011768:Pyruvate Dehydrogenase Complex / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology
D011768:Pyruvate Dehydrogenase Complex; C008046:5-hydroxymethylfurfural; D019289:Pyruvic Acid; D005662:Furaldehyde; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase