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Literature summary extracted from

  • Wang, B.; Chen, X.; Wang, Z.; Xiong, W.; Xu, T.; Zhao, X.; Cao, Y.; Guo, Y.; Li, L.; Chen, S.; Huang, S.; Wang, X.; Fang, M.; Shen, Z.
    Aldehyde dehydrogenase 1A1 increases NADH levels and promotes tumor growth via glutathione/dihydrolipoic acid-dependent NAD+ reduction (2017), Oncotarget, 8, 67043-67055 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.2.1.36 recombinant H1299 cells expressing C302A, E107G, and I304K mutant forms of ALDH1A1 lack aldehyde-dehydrogenase activity Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
1.2.1.5 additional information simultaneous knockout of ALDH1A1 (EC 1.2.1.36) and its isozyme ALDH3A1 in lung cancer cell line NCI-H460 inhibits tumor growth in a xenograft model. Moreover, the ALDH1A1 mutants that retain their GSH/DHLA-dependent NAD+ reduction activity and lose their aldehyde-dehydrogenase activity are able to decrease the NAD+/NADH ratio and to rescue the impaired growth of ALDH1A1/3A1 double knockout tumor cells Homo sapiens
1.2.1.36 C302A site-directed mutagenesis of catalytic active center residue, the mutant ALDH1A1 loses both activities Homo sapiens
1.2.1.36 C303A site-directed mutagenesis of catalytic active center residue, the mutant ALDH1A1 loses both activities Homo sapiens
1.2.1.36 C456A site-directed mutagenesis of a cysteine residue outside the active center, the mutation has no effect on both the aldehyde-dehydrogenase activity and the GSH/DHLA-dependent NAD+-reduction activity Homo sapiens
1.2.1.36 E107G site-directed mutagenesis, mutation of a residue that contributes to conformational integrity, the mutant loses its aldehyde-dehydrogenase activity, yet completely retains its GSH/DHLA-dependent NAD+-reduction activity Homo sapiens
1.2.1.36 G246A/G251A site-directed mutagenesis of NAD+-binding sites, the mutant ALDH1A1 loses both the aldehyde-dehydrogenase activity and the GSH/DHLA-dependent NAD+-reduction activity Homo sapiens
1.2.1.36 I304K site-directed mutagenesis, the mutant loses its aldehyde-dehydrogenase activity Homo sapiens
1.2.1.36 additional information ectopic expression of ALDH1A1 decreases the intracellular NAD+/NADH ratio, while knockout of ALDH1A1 increases the NAD+/NADH ratio. Simultaneous knockout of ALDH1A1 and its isozyme ALDH3A1 (EC 1.2.1.5) in lung cancer cell line NCI-H460 inhibits tumor growth in a xenograft model. Moreover, the ALDH1A1 mutants that retain their GSH/DHLA-dependent NAD+ reduction activity and lose their aldehyde-dehydrogenase activity are able to decrease the NAD+/NADH ratio and to rescue the impaired growth of ALDH1A1/3A1 double knockout tumor cells. H-1299 cells expressing C302A, E107G, and I304K mutant forms of ALDH1A1 lack aldehyde-dehydrogenase activity Homo sapiens
1.2.1.36 W178E/I304K site-directed mutagenesis, mutation of aldehyde binding residues W178 and I304, the mutant loses its aldehyde-dehydrogenase activity, yet completely retains its GSH/DHLA-dependent NAD+-reduction activity Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.2.1.36 diethylaminobenzaldehyde DEAB, an ALDH1A1 inhibitor which competitively binds to the aldehyde-binding pocket of ALDH1A1 and completely inhibits the aldehyde oxidation activity of the enzyme at 0.01 mM, but has no effect on the GSH/DHLA-dependent NAD+-reduction activity Homo sapiens
1.2.1.36 Mg2+ inhibits the aldehyde dehydrogenase activity of ALDH1A1 by inhibiting the dissociation of NADH from the enzyme Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
1.2.1.36 cytosol
-
 Homo sapiens 5829
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
1.2.1.36 MgCl2 promotes the GSH/DHLA-dependent NAD+-reduction activity in a dose-dependent manner. Mg2+ exerts separate effects on the GSH/DHLA-dependent NAD+-reduction activity and the aldehyde-dehydrogenase activity of ALDH1A1 Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.2.1.36 all-trans-retinal + H2O + NAD+ Homo sapiens
-
 all-trans-retinoate + NADH + 2 H+
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.2.1.5 Homo sapiens P30838
-
-
1.2.1.36 Homo sapiens P00352
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
1.2.1.5 purification of the enzyme(s) responsible for the GSH/DHLA-dependent NAD+ reduction activity from large-scale cell cultures, native enzyme from EKVX lung cancer cells by ultracentrifugation of crude cell extract and anion echange chromatography, hydrophobic interaction and hydroxyapatite chromatography, followed by gel filtration and another different step of anion exchange chromatography Homo sapiens
1.2.1.36 purification of the enzyme(s) responsible for the GSH/DHLA-dependent NAD+ reduction activity from large-scale cell cultures, native enzyme from EKVX lung cancer cells by ultracentrifugation of crude cell extract and anion echange chromatography, hydrophobic interaction and hydroxyapatite chromatography, followed by gel filtration and another different step of anion exchange chromatography Homo sapiens

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.2.1.5 A-549 cell
-
 Homo sapiens
-
1.2.1.5 EKVX cell
-
 Homo sapiens
-
1.2.1.5 lung cancer cell
-
 Homo sapiens
-
1.2.1.5 additional information ALDH3A1 is highly expressed in lung carcinoma cell line A549 and EKVX, as well as in the large cell carcinoma cell line H460. Isozyme ALDH1A1 (EC 1.2.1.36) shows a similar expression pattern like ALDH3A1. Other members of the aldehyde dehydrogenase family are not expressed in the lung cancer cell lines examined Homo sapiens
-
1.2.1.5 NCI-H460 cell
-
 Homo sapiens
-
1.2.1.36 A-549 cell
-
 Homo sapiens
-
1.2.1.36 EKVX cell
-
 Homo sapiens
-
1.2.1.36 lung cancer cell
-
 Homo sapiens
-
1.2.1.36 additional information ALDH1A1 is highly expressed in lung carcinoma cell line A549 and EKVX, as well as in the large cell carcinoma cell line H460. Isozyme ALDH3A1 (EC 1.2.1.5) shows a similar expression pattern like ALDH1A1. Other members of the aldehyde dehydrogenase family are not expressed in the lung cancer cell lines examined Homo sapiens
-
1.2.1.36 NCI-H460 cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.2.1.5 2 glutathione + NAD+
-
 Homo sapiens GSSG + NADH + H+
-
 ?
1.2.1.5 dihydrolipoic acid + NAD+
-
 Homo sapiens alpha-lipoic acid + NADH + H+
-
 ?
1.2.1.5 additional information ALDH1A1 can also use glutathione (GSH) and dihydrolipoic acid (DHLA) as electron donors to reduce NAD+ to NADH, product identification by thin layer chromatography (TLC) Homo sapiens ?
-
-
1.2.1.36 all-trans-retinal + H2O + NAD+
-
 Homo sapiens all-trans-retinoate + NADH + 2 H+
-
 ?
1.2.1.36 dihydrolipoic acid + H2O + NAD+
-
 Homo sapiens ? + NADH + 2 H+
-
 ?
1.2.1.36 glutathione + H2O + NAD+
-
 Homo sapiens GSSG + NADH + 2 H+
-
 ?
1.2.1.36 additional information the dissociation of NADH from the enzyme is the rate-limiting step for ALDH1A1-mediated aldehyde oxidation. ALDH1A1 can also use glutathione (GSH) and dihydrolipoic acid (DHLA) as electron donors to reduce NAD+ to NADH, product identification by thin layer chromatography (TLC). Even though they share the same NAD+-binding sites and the same active sites, the enzymatic mechanism of the GSH/DHLA-dependent NAD+-reduction activity of ALDH1A1 is distinct from its aldehyde-dehydrogenase activity Homo sapiens ?
-
-

Subunits

EC Number Subunits Comment Organism
1.2.1.36 ? x * 60000, SDS-PAGE Homo sapiens

Synonyms

EC Number Synonyms Comment Organism
1.2.1.5 aldehyde dehydrogenase 3A1
-
 Homo sapiens
1.2.1.5 ALDH3A1
-
 Homo sapiens
1.2.1.36 aldehyde dehydrogenase 1A1
-
 Homo sapiens
1.2.1.36 ALDH1A1
-
 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
1.2.1.36 30
-
 assay at Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
1.2.1.5 NAD+
-
 Homo sapiens
1.2.1.36 NAD+
-
 Homo sapiens

General Information

EC Number General Information Comment Organism
1.2.1.5 evolution aldehyde dehydrogenase 1A1 (ALDH3A1) is a member of the aldehyde dehydrogenase superfamily that oxidizes aldehydes to their corresponding acids, reactions that are coupled to the reduction of NAD(P)+ to NAD(P)H Homo sapiens
1.2.1.5 metabolism ALDH1A1 and ALDH3A1 have the same GSH/DHLA-dependent NAD+-reduction activity Homo sapiens
1.2.1.5 physiological function aldehyde dehydrogenase 3A1 increases NADH levels and promotes tumor growth via glutathione/dihydrolipoic acid-dependent NAD+ reduction. ALDH3A1 can also use glutathione (GSH) and dihydrolipoic acid (DHLA) as electron donors to reduce NAD+ to NADH. The GSH/DHLA-dependent NAD+-reduction activity of ALDH1A1 is not affected by the aldehyde dehydrogenase inhibitor or by mutation of the residues in its aldehyde-binding pocket. It is thus a distinct biochemical reaction from the classic aldehyde-dehydrogenase activity catalyzed by ALDH3A1. The GSH/DHLA-dependent NAD+-reduction activity of ALDH3A1 can decrease cellular NAD+/NADH ratio and promote tumor growth Homo sapiens
1.2.1.36 evolution aldehyde dehydrogenase 1A1 (ALDH1A1) is a member of the aldehyde dehydrogenase superfamily that oxidizes aldehydes to their corresponding acids, reactions that are coupled to the reduction of NAD+ to NADH Homo sapiens
1.2.1.36 malfunction H-1299 cells expressing C302A, E107G, and I304K mutant forms of ALDH1A1 lacked aldehyde-dehydrogenase activity Homo sapiens
1.2.1.36 metabolism ALDH1A1 and ALDH3A1 have the same GSH/DHLA-dependent NAD+-reduction activity Homo sapiens
1.2.1.36 physiological function aldehyde dehydrogenase 1A1 increases NADH levels and promotes tumor growth via glutathione/dihydrolipoic acid-dependent NAD+ reduction. ALDH1A1 can also use glutathione (GSH) and dihydrolipoic acid (DHLA) as electron donors to reduce NAD+ to NADH. The GSH/DHLA-dependent NAD+-reduction activity of ALDH1A1 is not affected by the aldehyde dehydrogenase inhibitor or by mutation of the residues in its aldehyde-binding pocket. It is thus a distinct biochemical reaction from the classic aldehyde-dehydrogenase activity catalyzed by ALDH1A1. The GSH/DHLA-dependent NAD+-reduction activity of ALDH1A1 can decrease cellular NAD(P)+/NAD(P)H ratio and promote tumor growth. The tumor-promoting effect of ALDH1A1 is achieved, at least partially, through decreasing the cellular NAD+/ NADH ratio Homo sapiens