Topic
Aldehyde dehydrogenase
About: Aldehyde dehydrogenase is a research topic. Over the lifetime, 3365 publications have been published within this topic receiving 107683 citations.
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TL;DR: Test the hypothesis that the ALDH2 reaction is sufficient for GTN bioactivation and measured GTN-induced formation of cGMP by purified sGC in the presence of purified AlDH2 and used a Clark-type electrode to probe for nitric oxide (NO) formation, to explain the coupling of AL DH2-catalyzed GTN metabolism to sGC activation in vascular smooth muscle.
75 citations
TL;DR: It is shown that an excellent correlation exists between the apparent molecular weight and the specific activity of the enzyme at any M&+ concentration.
75 citations
Journal Article•
TL;DR: In this article, aldehyde dehydrogenase 6 (ALDH6) was identified as the enzyme responsible for the loss of RA synthesis ability in cancer cells and the relationship of this process to malignant transformation.
Abstract: Retinoic acid (RA) is the form of vitamin A that controls differentiation and proliferation of epithelia. Our previous work established that normal breast epithelia synthesize RA from retinol, an ability retained by three immortalized but nontumorigenic cell lines but lost in five of six breast cell lines. In this work, we characterize the cause of this defect in one of the lines, the MCF-7 line. We have determined that the immortalized but nontumorigenic cell line, MTSV1.7, capable of synthesizing RA from both retinol and retinal, contains a retinaldehyde dehydrogenase activity for the second step in RA biosynthesis. We have identified it, after isolation, as a previously described enzyme, aldehyde dehydrogenase 6 (ALDH6). Immunohistochemical analysis of normal human breast with antibodies to ALDH6 showed expression of this enzyme in the glandular epithelia colocalized with cellular RA-binding protein type II, a possible marker for certain cells able to synthesize RA. ALDH6 was not present in MCF-7 cells, and these cells were unable to oxidize retinal to RA in culture. When MCF-7 cells were then transfected with ALDH6, they (re)gained the ability to oxidize retinal to RA as well as some ability to synthesize RA when provided with retinol. This suggests that loss of ALDH6 expression is the defect in RA biosynthesis in these cells. Identification of ALDH6 as the retinaldehyde dehydrogenase present in normal human breast epithelia provides the first tool necessary for studying the loss of RA synthetic ability in cancer cells and the relationship of this process to malignant transformation.
75 citations
TL;DR: The discovery of a general class of ALDH inhibitors with a common mechanism of action is reported, and it is demonstrated that these inhibitors undergo an enzyme-mediated β-elimination reaction generating a vinyl ketone intermediate that covalently modifies the active site cysteine residue present in these enzymes.
75 citations
TL;DR: The lexicon of vitamin K ω-hydroxylases is expanded to include the 'orphan' P450 CYP4F11 and a common variant, CYP 4F2, is identified as a major pharmacogenetic variable influencing MK4 catabolism.
Abstract: Vitamin K plays an essential role in many biological processes including blood clotting, maintenance of bone health, and inhibition of arterial calcification A menaquinone form of vitamin K, MK4, is increasingly recognized for its key roles in mitochondrial electron transport, as a ligand for the nuclear receptor SXR, which controls the expression of genes involved in transport and metabolism of endo- and xenobiotics, and as a pharmacotherapeutic in the treatment of osteoporosis Although cytochrome P450 (CYP) 4F2 activity is recognized as an important determinant of phylloquinone (K1) metabolism, the enzymes involved in menaquinone catabolism have not been studied previously CYP4F2 and CYP4F11 were expressed and purified and found to be equally efficient as in vitro catalysts of MK4 ω- hydroxylation CYP4F2, but not CYP4F11, catalyzed sequential metabolism of MK4 to the ω- acid without apparent release of the intermediate aldehyde The ω-alcohol could also be metabolized to the acid by microsomal NAD + -dependent alcohol and aldehyde dehydrogenases LC−MS/MS analysis of trypsinized human liver microsomes (using a surrogate peptide approach) revealed the mean concentrations of CYP4F2 and CYP4F11 to be 143 and 84 pmol/mg protein, respectively Microsomal MK4 ω-hydroxylation activities correlated with the CYP4F2 V433M genotype but not the CYP4F11 D446N genotype Collectively, these data expand the lexicon of vitamin K ω-hydroxylases to include the 'orphan' P450 CYP4F11 and identify a common variant, CYP4F2 (rs2108622), as a major pharmacogenetic variable influencing MK4 catabolism
75 citations