Activation of Human Salivary Aldehyde Dehydrogenase by Sulforaphane: Mechanism and Significance.
Cruciferous vegetables contain the bio-active compound sulforaphane (SF) which has been reported to protect individuals against various diseases by a number of mechanisms, including activation of the phase II detoxification enzymes. In this study, we show that the extracts of five cruciferous vegeta...
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doaj-ee8fd974e3ad4fa0bc9358a622e191ec2020-11-25T00:08:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-011112e016846310.1371/journal.pone.0168463Activation of Human Salivary Aldehyde Dehydrogenase by Sulforaphane: Mechanism and Significance.Md Fazle AlamAmaj Ahmed LaskarLubna MaryamHina YounusCruciferous vegetables contain the bio-active compound sulforaphane (SF) which has been reported to protect individuals against various diseases by a number of mechanisms, including activation of the phase II detoxification enzymes. In this study, we show that the extracts of five cruciferous vegetables that we commonly consume and SF activate human salivary aldehyde dehydrogenase (hsALDH), which is a very important detoxifying enzyme in the mouth. Maximum activation was observed at 1 μg/ml of cabbage extract with 2.6 fold increase in the activity. There was a ~1.9 fold increase in the activity of hsALDH at SF concentration of ≥ 100 nM. The concentration of SF at half the maximum response (EC50 value) was determined to be 52 ± 2 nM. There was an increase in the Vmax and a decrease in the Km of the enzyme in the presence of SF. Hence, SF interacts with the enzyme and increases its affinity for the substrate. UV absorbance, fluorescence and CD studies revealed that SF binds to hsALDH and does not disrupt its native structure. SF binds with the enzyme with a binding constant of 1.23 x 107 M-1. There is one binding site on hsALDH for SF, and the thermodynamic parameters indicate the formation of a spontaneous strong complex between the two. Molecular docking analysis depicted that SF fits into the active site of ALDH3A1, and facilitates the catalytic mechanism of the enzyme. SF being an antioxidant, is very likely to protect the catalytic Cys 243 residue from oxidation, which leads to the increase in the catalytic efficiency and hence the activation of the enzyme. Further, hsALDH which is virtually inactive towards acetaldehyde exhibited significant activity towards it in the presence of SF. It is therefore very likely that consumption of large quantities of cruciferous vegetables or SF supplements, through their activating effect on hsALDH can protect individuals who are alcohol intolerant against acetaldehyde toxicity and also lower the risk of oral cancer development.http://europepmc.org/articles/PMC5172892?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Md Fazle Alam Amaj Ahmed Laskar Lubna Maryam Hina Younus |
spellingShingle |
Md Fazle Alam Amaj Ahmed Laskar Lubna Maryam Hina Younus Activation of Human Salivary Aldehyde Dehydrogenase by Sulforaphane: Mechanism and Significance. PLoS ONE |
author_facet |
Md Fazle Alam Amaj Ahmed Laskar Lubna Maryam Hina Younus |
author_sort |
Md Fazle Alam |
title |
Activation of Human Salivary Aldehyde Dehydrogenase by Sulforaphane: Mechanism and Significance. |
title_short |
Activation of Human Salivary Aldehyde Dehydrogenase by Sulforaphane: Mechanism and Significance. |
title_full |
Activation of Human Salivary Aldehyde Dehydrogenase by Sulforaphane: Mechanism and Significance. |
title_fullStr |
Activation of Human Salivary Aldehyde Dehydrogenase by Sulforaphane: Mechanism and Significance. |
title_full_unstemmed |
Activation of Human Salivary Aldehyde Dehydrogenase by Sulforaphane: Mechanism and Significance. |
title_sort |
activation of human salivary aldehyde dehydrogenase by sulforaphane: mechanism and significance. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2016-01-01 |
description |
Cruciferous vegetables contain the bio-active compound sulforaphane (SF) which has been reported to protect individuals against various diseases by a number of mechanisms, including activation of the phase II detoxification enzymes. In this study, we show that the extracts of five cruciferous vegetables that we commonly consume and SF activate human salivary aldehyde dehydrogenase (hsALDH), which is a very important detoxifying enzyme in the mouth. Maximum activation was observed at 1 μg/ml of cabbage extract with 2.6 fold increase in the activity. There was a ~1.9 fold increase in the activity of hsALDH at SF concentration of ≥ 100 nM. The concentration of SF at half the maximum response (EC50 value) was determined to be 52 ± 2 nM. There was an increase in the Vmax and a decrease in the Km of the enzyme in the presence of SF. Hence, SF interacts with the enzyme and increases its affinity for the substrate. UV absorbance, fluorescence and CD studies revealed that SF binds to hsALDH and does not disrupt its native structure. SF binds with the enzyme with a binding constant of 1.23 x 107 M-1. There is one binding site on hsALDH for SF, and the thermodynamic parameters indicate the formation of a spontaneous strong complex between the two. Molecular docking analysis depicted that SF fits into the active site of ALDH3A1, and facilitates the catalytic mechanism of the enzyme. SF being an antioxidant, is very likely to protect the catalytic Cys 243 residue from oxidation, which leads to the increase in the catalytic efficiency and hence the activation of the enzyme. Further, hsALDH which is virtually inactive towards acetaldehyde exhibited significant activity towards it in the presence of SF. It is therefore very likely that consumption of large quantities of cruciferous vegetables or SF supplements, through their activating effect on hsALDH can protect individuals who are alcohol intolerant against acetaldehyde toxicity and also lower the risk of oral cancer development. |
url |
http://europepmc.org/articles/PMC5172892?pdf=render |
work_keys_str_mv |
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