Retinal Oxidation Activity and Biological Role of Human Cytosolic Aldehyde Dehydrogenase

Abstract

The major cytosolic aldehyde dehydrogenase isozyme (ALDH1) exhibits strong activity for oxidation of retinal to retinoic acid, while the major mitochondrial ALDH2 and the stomach cytosolic ALDH3 have no such activity. The K(m) of ALDH1 for retinal is about 0.06 μmol/l at pH 7.5, and the catalytic efficiency (Vmax/Km) for retinal is about 600 times higher than that for acetaldehyde. Thus, ALDH1 can efficiently produce retinoic acid from retinal in tissues with low retinal concentrations (<0.1 μmol/l). The gene for ALDH1 has hormone response elements. These findings suggest that the major physiological substrate of human ALDH1 is retinal, and that its primary biological role is generation of retinoic acid resulting in modulation of cell differentiation including hormone-mediated development.

Xenopus Cytosolic Thyroid Hormone-binding Protein (xCTBP) Is Aldehyde Dehydrogenase Catalyzing the Formation of Retinoic Acid

“…This analysis supports the specific branching orders for the major groups, which are ((ALDH6, ALDH1) and (ALDH5, ALDH2)), ALDH9) as shown in the tree by Yoshida et al (62). Proteins with catalytic activity converting retinal to RA are indicated by asterisks (20,22,23,38,39,45,(52)(53)(54)(55)57 …”

CD44 and CD24 cannot act as cancer stem cell markers in human lung adenocarcinoma cell line A549

“…Although previous studies have demonstrated that CD133 and CD44 are the most robust markers for lung CSCs, their co-expression has not yet been evaluated in lung cancer. CSCs can also be identified or isolated using the activity of aldehyde dehydrogenase 1 (ALDH1), which is involved in the detoxification of intracellular aldehydes, oxidation of retinol to retinoic acid, and early stem cell differentiation [16]. Some recent studies demonstrated that ALDH1 + lung cancer cells display in vitro and in vivo CSC features, so ALDH1is identified as a lung cancer stem cell-associated marker [17,18].…”

Structural shifts of aldehyde dehydrogenase enzymes were instrumental for the early evolution of retinoid-dependent axial patterning in metazoans

“…Thus, SEC topology influences ALDH1/2 substrate preference. For example, although retinaldehyde is a good substrate for vertebrate ALDH1s and acetaldehyde is a natural substrate of ALDH2s, ALDH2s cannot process retinaldehyde and ALDH1s process acetaldehyde only extremely inefficiently (16,(17)(18)(19)(20)(21)(22).To understand the evolutionary origins of the substrate preferences of ALDH1 and ALDH2 enzymes, as well as to illuminate how signaling and protective functions are connected to these different enzyme activities, we used an integrated approach that combined genomic, phylogenetic, and structural analyses. The resulting comprehensive data set was complemented with information on developmental gene expression of ALDH1/2s in the cephalochordate amphioxus (Branchiostoma floridae) and the ascidian tunicate Ciona intestinalis.…”

“…Thus, SEC topology influences ALDH1/2 substrate preference. For example, although retinaldehyde is a good substrate for vertebrate ALDH1s and acetaldehyde is a natural substrate of ALDH2s, ALDH2s cannot process retinaldehyde and ALDH1s process acetaldehyde only extremely inefficiently (16,(17)(18)(19)(20)(21)(22).…”

“…Thus, structural modeling of these proteins can be used to study the evolution of substrate specificity without extensive biochemical analyses (16)(17)(18)(19)(20).…”