ALDH2 Mouse, Active
Description
Molecular and Biochemical Properties
ALDH2 Mouse, Active is a recombinant protein expressed in E. coli, consisting of 523 amino acids (residues 20–519) with an N-terminal His-tag. Key characteristics include:
| Property | Details |
|---|---|
| Molecular Weight | 56.8 kDa |
| Purity | >95% (SDS-PAGE) |
| Formulation | Phosphate-buffered saline (pH 7.4), 20% glycerol, 1 mM DTT |
| Specific Activity | >180 pmol/min/μg (measured via NADH absorbance at 340 nm) |
| Biological Function | Catalyzes oxidation of aldehydes (e.g., acetaldehyde, 4-HNE) to carboxylic acids using NAD⁺ |
This recombinant enzyme retains functional activity comparable to native ALDH2, making it suitable for in vitro assays .
Enzymatic Assays
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Substrate Specificity: Efficiently oxidizes short-chain aliphatic aldehydes (e.g., acetaldehyde) and toxic lipid peroxidation products like 4-HNE .
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Kinetic Studies: Used to measure NAD⁺-dependent activity, with applications in studying ALDH2 inhibitors or activators (e.g., Alda-1, AD-9308) .
Therapeutic Research
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Pain Management: ALDH2 activation with Alda-1 reduces nociception in rodent models by lowering reactive aldehyde levels (e.g., 4-HNE) .
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Neuroprotection: Enhances clearance of neurotoxic aldehydes in Alzheimer’s disease (AD) models, mitigating mitochondrial dysfunction and cognitive decline .
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Cardioprotection: Improves cardiac function in ischemia-reperfusion injury models by reducing 4-HNE adducts .
Role in Nociception
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Heterozygous ALDH2*1/2 mice (mimicking human ALDH22 mutation) exhibit heightened pain sensitivity due to elevated 4-HNE levels. Alda-1 treatment normalizes nociceptive responses by restoring ALDH2 activity .
Impact on Alzheimer’s Disease
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ALDH2-deficient mice show accelerated AD pathology, including Aβ accumulation and tau hyperphosphorylation. Overexpression of wild-type ALDH2 or treatment with Alda-1 reduces 4-HNE levels and improves cognitive function .
Metabolic Disorders
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ALDH2*2 knock-in mice develop diet-induced obesity and insulin resistance. Chronic administration of ALDH2 activators (e.g., AD-9308) reverses these effects by enhancing aldehyde detoxification .
Comparative Studies in Models
Therapeutic Implications
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Alda-1: A small-molecule activator that restores ALDH2 activity in mutant models, showing efficacy in pain, cardiac injury, and neurodegenerative disorders .
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AD-9308: A prodrug of AD-5591, a next-generation ALDH2 activator with improved solubility and oral bioavailability, currently under investigation for metabolic syndrome .
Limitations and Future Directions
Product Specs
This recombinant ALDH2 protein was expressed in E. coli and purified. It is a single, non-glycosylated polypeptide chain with a molecular weight of 56.8 kDa. The protein sequence includes amino acids 20-519 of the mouse ALDH2 protein, along with a 23 amino acid His-tag at the N-terminus.
Purification was achieved using proprietary chromatographic techniques.
MGSSHHHHHH SSGLVPRGSH MGSSAAATSA VPAPNHQPEV FCNQIFINNE WHDAVSRKTF PTVNPSTGEV ICQVAEGNKE DVDKAVKAARAAFQLGSPWR RMDASDRGRL LYRLADLIER DRTYLAALET LDNGKPYVIS YLVDLDMVLK CLRYYAGWAD KYHGKTIPID GDFFSYTRHEPVGVCGQIIP WNFPLLMQAW KLGPALATGN VVVMKVAEQT PLTALYVANL IKEAGFPPGV VNIVPGFGPT AGAAIASHEG VDKVAFTGSTEVGHLIQVAA GSSNLKRVTL ELGGKSPNII MSDADMDWAV EQAHFALFFN QGQCCCAGSR TFVQENVYDE FVERSVARAK SRVVGNPFDSRTEQGPQVDE TQFKKILGYI KSGQQEGAKL LCGGGAAADR GYFIQPTVFG DVKDGMTIAK EEIFGPVMQI LKFKTIEEVV GRANDSKYGLAAAVFTKDLD KANYLSQALQ AGTVWINCYD VFGAQSPFGG YKMSGSGREL GEYGLQAYTE VKTVTVKVPQ KNS.
Product Science Overview
Aldehyde Dehydrogenase 2 (ALDH2) is a crucial enzyme in the aldehyde dehydrogenase family, playing a significant role in the oxidative pathway of alcohol metabolism. This enzyme is responsible for converting acetaldehyde, a toxic byproduct of alcohol metabolism, into acetic acid, which is less harmful to the body .
The mouse recombinant ALDH2 is produced in E. coli and is a single, non-glycosylated polypeptide chain containing 523 amino acids. It has a molecular mass of approximately 56.8 kDa and includes a 23 amino acid His-tag at the N-terminus for purification purposes . The enzyme is expressed in various tissues, including the liver, where it plays a pivotal role in detoxifying aldehydes generated from alcohol and other metabolic processes .
ALDH2 is the second enzyme in the major oxidative pathway of alcohol metabolism. It is essential for the detoxification of acetaldehyde, which, if accumulated, can cause cellular damage and contribute to conditions such as alcohol-induced liver disease . The enzyme’s activity is crucial for preventing acetaldehyde-induced cell injury and inhibiting the activation of stress signals .
Mutations in the ALDH2 gene can lead to a deficiency in enzyme activity, which is particularly prevalent in East Asian populations. This deficiency is associated with an increased risk of alcohol-related health issues, including a higher frequency of acute alcohol intoxication and a predisposition to certain cancers . The recombinant form of ALDH2 is used in research to study these effects and to develop potential therapeutic interventions.
Recombinant ALDH2 is widely used in biochemical and pharmacological research. It serves as a model to understand the enzyme’s structure-function relationship, investigate the impact of genetic mutations, and explore potential drug interactions. The recombinant enzyme is also employed in studies aimed at developing treatments for conditions related to ALDH2 deficiency .
