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 | 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 | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
mitochondrion | - |
Saccharomyces cerevisiae | 5739 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
K+ | activates | Saccharomyces cerevisiae |
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 | UniProt | Comment | Textmining |
---|---|---|---|
Saccharomyces cerevisiae | P46367 | - |
- |
Saccharomyces cerevisiae ATCC 204508 | P46367 | - |
- |
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 | Comment | Organism |
---|---|---|
ALD4 | - |
Saccharomyces cerevisiae |
NAD+-dependent Ald4 | - |
Saccharomyces cerevisiae |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NAD+ | preferred before NADP+ | Saccharomyces cerevisiae | |
NADP+ | - |
Saccharomyces cerevisiae |
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 |