Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme critical in detoxifying reactive aldehydes, particularly acetaldehyde—a toxic byproduct of ethanol metabolism. It also plays a role in metabolizing lipid peroxidation-derived aldehydes, such as 4-hydroxynonenal, which are linked to oxidative stress and cellular damage. ALDH2 is highly expressed in the liver, heart, and brain, and its dysfunction is associated with various diseases, including cardiovascular disorders, neurodegenerative conditions, and alcohol-related pathologies. A common genetic variant (Glu504Lys, rs671), prevalent in East Asian populations, reduces ALDH2 activity by ~90%, leading to "alcohol flush syndrome" and increased susceptibility to conditions like esophageal cancer and myocardial infarction.
Recombinant ALDH2 protein is engineered using expression systems like *E. coli*, yeast, or mammalian cells to produce purified, functional enzyme for research and therapeutic applications. Its production enables detailed structural studies (e.g., crystallography) to elucidate substrate binding and catalytic mechanisms. Researchers use recombinant ALDH2 to screen activators or inhibitors, aiming to develop drugs targeting ALDH2-deficient conditions or alcohol use disorders. For instance, small-molecule activators (e.g., Alda-1) have been explored to enhance mutant ALDH2 activity, potentially mitigating ischemia-reperfusion injury or alcohol toxicity. Additionally, recombinant ALDH2 serves as a biomarker in studies linking aldehyde accumulation to age-related diseases. Challenges include preserving post-translational modifications and mitochondrial localization in vitro, which are essential for its native function. Overall, recombinant ALDH2 is a vital tool for advancing therapeutic strategies against aldehyde-mediated toxicity and genetic susceptibility syndromes.
以下是关于ALDH3A1重组蛋白的3篇文献摘要示例(文献信息为模拟，仅供参考)：
1. **文献名称**：*Recombinant ALDH3A1 Expression in E. coli: Purification and Characterization*
**作者**：Smith J, et al.
**摘要**：该研究报道了在大肠杆菌中高效表达人源ALDH3A1重组蛋白的方法，通过亲和层析纯化获得高纯度蛋白，并验证其催化氧化乙醛的酶活性及稳定性。
2. **文献名称**：*ALDH3A1 Protects Lung Cells from Oxidative Stress via NADPH Regulation*
**作者**：Chen L, et al.
**摘要**：通过体外重组ALDH3A1蛋白实验，证明其通过调节NADPH水平减轻肺癌细胞氧化损伤，提示其在癌症细胞耐药性中的潜在作用。
3. **文献名称**：*Structural Insights into ALDH3A1 Substrate Specificity*
**作者**：Kim H, et al.
**摘要**：利用重组ALDH3A1蛋白的晶体结构解析，揭示其底物结合域的关键氨基酸残基，为设计靶向抑制剂提供结构基础。
4. **文献名称**：*ALDH3A1 Recombinant Protein Attenuates Liver Fibrosis in Mice*
**作者**：Wang Y, et al.
**摘要**：在小鼠模型中，外源性重组ALDH3A1蛋白通过清除毒性醛类化合物，显著减轻酒精诱导的肝纤维化，提示其治疗潜力。
(注：以上文献信息为生成内容，实际引用需查询PubMed、Web of Science等数据库获取真实文献。)
ALDH3A1 (Aldehyde Dehydrogenase 3 Family Member A1) is a member of the aldehyde dehydrogenase superfamily, which plays a critical role in detoxifying endogenous and exogenous aldehydes by catalyzing their oxidation to carboxylic acids. This NAD(P)+-dependent enzyme is highly expressed in tissues exposed to oxidative stress, such as the cornea, liver, and certain cancer cells. It contributes to cellular defense mechanisms by metabolizing toxic lipid peroxidation products (e.g., 4-hydroxynonenal) and reactive aldehydes generated during drug metabolism. ALDH3A1 also exhibits non-enzymatic functions, including antioxidant activity, modulation of cell proliferation, and protection against UV-induced damage, making it a multifunctional protein.
Recombinant ALDH3A1 protein is produced using heterologous expression systems (e.g., *E. coli*, insect, or mammalian cells*) to enable detailed biochemical and structural studies. Its recombinant form retains enzymatic activity and structural integrity, allowing researchers to investigate substrate specificity, kinetic properties, and interactions with inhibitors or cofactors. Crystallographic studies reveal a conserved tertiary structure with a catalytic domain, NAD(P)+-binding site, and substrate channel, aiding in the design of targeted therapies.
In research, recombinant ALDH3A1 is used to explore its role in diseases like cancer (e.g., chemoresistance in stem cells), cataracts, and metabolic disorders. It also serves as a biomarker for oxidative stress-related conditions and a potential therapeutic target. The development of ALDH3A1 inhibitors or activators could offer novel strategies for treating diseases linked to aldehyde overload or dysregulated detoxification pathways.
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