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Literature summary for 1.2.1.5 extracted from

  • Zhang, Y.; Wang, M.; Lin, H.
    A regulatory cysteine residue mediates reversible inactivation of NAD+-dependent aldehyde dehydrogenases to promote oxidative stress response (2020), ACS Chem. Biol., 15, 28-32 .
    View publication on PubMed
Search for more literature for 1.2.1.5

Cloned(Commentary)

Cloned (Comment) Organism
gene ald4, recombinant expression of wild-type Ald4 and mutant Ald4 C325S enzymes, as well as Ald4 knockout (DELTAald4) strain under the original promoter of Ald4 Saccharomyces cerevisiae

Protein Variants

Protein Variants Comment Organism
C325S site-directed mutagenesis, the mutant strain is more sensitive against H2O2 treatment than the wild-type and shows lower NADPH concentration Saccharomyces cerevisiae
additional information construction of an Ald4 knockout (DELTAald4) strain, the mutant strain is more sensitive against H2O2 treatment than the wild-type Saccharomyces cerevisiae

Localization

Localization Comment Organism GeneOntology No. Textmining
mitochondrion
-
 Saccharomyces cerevisiae 5739
-

Metals/Ions

Metals/Ions Comment Organism Structure
K+ activates Saccharomyces cerevisiae

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
acetaldehyde + NAD+ + H2O Saccharomyces cerevisiae
-
 acetate + NADH + H+
-
 ?
acetaldehyde + NAD+ + H2O Saccharomyces cerevisiae ATCC 204508
-
 acetate + NADH + H+
-
 ?
acetaldehyde + NADP+ + H2O Saccharomyces cerevisiae
-
 acetate + NADPH + H+
-
 ?
acetaldehyde + NADP+ + H2O Saccharomyces cerevisiae ATCC 204508
-
 acetate + NADPH + H+
-
 ?

Organism

Organism UniProt Comment Textmining
Saccharomyces cerevisiae P46367
-
-
Saccharomyces cerevisiae ATCC 204508 P46367
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
acetaldehyde + NAD+ + H2O
-
 Saccharomyces cerevisiae acetate + NADH + H+
-
 ?
acetaldehyde + NAD+ + H2O
-
 Saccharomyces cerevisiae ATCC 204508 acetate + NADH + H+
-
 ?
acetaldehyde + NADP+ + H2O
-
 Saccharomyces cerevisiae acetate + NADPH + H+
-
 ?
acetaldehyde + NADP+ + H2O
-
 Saccharomyces cerevisiae ATCC 204508 acetate + NADPH + H+
-
 ?

Synonyms

Synonyms Comment Organism
ALD4
-
 Saccharomyces cerevisiae
NAD+-dependent Ald4
-
 Saccharomyces cerevisiae

Cofactor

Cofactor Comment Organism Structure
NAD+ preferred before NADP+ Saccharomyces cerevisiae
NADP+
-
 Saccharomyces cerevisiae

General Information

General Information Comment Organism
evolution physiological function of the regulatory mechanism for NAD+-dependent ALDHs via cysteine oxidation and vicinal disulfide formation using yeast Ald4 (EC 1.2.1.5) and Ald6. While both enzymes convert aldehyde to acetate and are important for yeast ethanol metabolism, they differ in cofactor utilization and the regulatory mechanism. Ald4 prefers NAD+ while Ald6 is NADP+-dependent. The regulation of activity via disulfide formation between the catalytic cysteine and adjacent regulatory cysteine is only present in the NAD+-dependent Ald4, but not in the NADP+-dependent Ald6. This regulatory mechanism for Ald4 ensures the fast inactivation of Ald4 upon oxidation and the reactivation upon reduction Saccharomyces cerevisiae
metabolism regulation of activity via disulfide formation between the catalytic cysteine and adjacent regulatory cysteine is only present in the NAD+-dependent Ald4, but not in the NADP+-dependent Ald6. This regulatory mechanism for Ald4 ensures the fast inactivation of Ald4 upon oxidation and the reactivation upon reduction. Isozymes Ald4, Ald5 and Ald6 play important roles in yeast survival when using ethanol as the carbon source. Both Ald4 and Ald5 preferentially use NAD+ as cofactors in cells while Ald6 only utilizes NADP+. With ethanol as the carbon source, the pentose phosphate pathway, a major pathway to generate NADPH, is shut down as the substrate is not available. Instead of cysteine, Ald6 has a serine next to the active site cysteine. As the regulatory cysteine inactivates Ald4 during oxidative stress, Ald6 remains active while Ald4 is inactivated, thus diverting all acetaldehyde to Ald6 for the production of NADPH. This way, yeast can survive oxidative stress better Saccharomyces cerevisiae
physiological function Ald4 converts aldehyde to acetate and are important for yeast ethanol metabolism Saccharomyces cerevisiae