ALDH - Aldehyde dehydrogenase family member | Elisa - Clia - Antibody - Protein

Background:

Aldehyde dehydrogenases (ALDHs) are a family of enzymes that play a crucial role in the metabolism of aldehydes. ALDH enzymes catalyze the oxidation of aldehydes to their corresponding carboxylic acids, utilizing NAD+ (nicotinamide adenine dinucleotide) or NADP+ (nicotinamide adenine dinucleotide phosphate) as cofactors. This oxidation reaction involves the removal of hydrogen atoms from the aldehyde substrate and the transfer of these hydrogen atoms to the cofactor, forming NADH or NADPH.The ALDH enzyme family is diverse, with multiple isoforms present in various tissues and cellular compartments. These isoforms have different substrate specificities, cellular localization, and physiological functions. Some key roles of ALDH enzymes include: Aldehyde Detoxification: ALDH enzymes play a crucial role in detoxifying reactive aldehydes that can be generated during various metabolic processes, environmental exposures, or as byproducts of oxidative stress. By converting these aldehydes into less toxic carboxylic acids, ALDH enzymes help protect cells from damage. Alcohol Metabolism: ALDH enzymes are involved in the metabolism of ethanol (alcohol) in the liver. They catalyze the oxidation of acetaldehyde, a toxic intermediate produced during alcohol metabolism, to acetate, which can be further metabolized or excreted . Oxidative Stress Response: Some ALDH isoforms have been implicated in cellular responses to oxidative stress. They can help mitigate oxidative damage by metabolizing reactive aldehydes generated as a result of oxidative stress.Neurotransmitter Metabolism: Certain ALDH isoforms are involved in the metabolism of neurotransmitters such as dopamine and serotonin. Dysregulation of these ALDH enzymes has been linked to neurological disorders such as Parkinson's disease and alcohol use disorders.

Protein Structure:

• General Structure: ALDHs typically function as homodimers or homotetramers, with each monomer consisting of an NAD(P)+ binding domain and an active site for aldehyde oxidation.
• Active Site: The active site contains a cysteine residue that acts as a nucleophile, facilitating the oxidation of aldehydes.
• Isozymes: The ALDH family includes several isozymes, each with specific structural features adapted to their unique substrates and cellular locations.

Classification and Subtypes:

• ALDH1A1: Involved in retinoic acid biosynthesis and stem cell differentiation.
• ALDH2: Primarily responsible for detoxifying acetaldehyde produced during alcohol metabolism.
• ALDH3A1: Plays a role in the metabolism of lipid peroxidation products and protection against oxidative stress.
• ALDH4A1: Involved in the metabolism of proline and hydroxyproline.
• ALDH5A1: Participates in the degradation of gamma-aminobutyric acid (GABA).
• ALDH6A1: Functions in the metabolism of valine, leucine, and isoleucine.
• ALDH7A1: Associated with the metabolism of lysine and protection against oxidative stress.
• ALDH9A1: Metabolizes aldehydes derived from amines and polyamines.

Function and Biological Significance:

• Detoxification: ALDHs oxidize toxic aldehydes to less harmful carboxylic acids, thus preventing cellular damage.
• Alcohol Metabolism: ALDH2 is crucial in metabolizing acetaldehyde, a toxic byproduct of alcohol metabolism. Deficiency in ALDH2 leads to an accumulation of acetaldehyde, causing alcohol intolerance.
• Retinoic Acid Synthesis: ALDH1A1, ALDH1A2, and ALDH1A3 are involved in the biosynthesis of retinoic acid, a vital molecule for cellular differentiation, proliferation, and apoptosis.
• Antioxidant Defense: ALDHs contribute to the defense against oxidative stress by metabolizing lipid peroxidation products.
• Neuroprotection: Certain ALDH isozymes protect neurons from oxidative damage and are involved in the metabolism of neurotransmitters.

Interactions:

• Cofactors: ALDHs require NAD+ or NADP+ as cofactors for their enzymatic activity.
• Substrate Specificity: Each ALDH isozyme has a specific substrate range, interacting with various aldehydes depending on their structure and cellular context.
• Protein-Protein Interactions: ALDHs can interact with other metabolic enzymes and proteins involved in signaling pathways, affecting their regulation and function.

Clinical Issues:

• Alcohol Intolerance: Deficiency in ALDH2 is common in East Asian populations, leading to an accumulation of acetaldehyde and symptoms like facial flushing, nausea, and tachycardia upon alcohol consumption.
• Cancer: ALDHs are considered markers for cancer stem cells and are involved in the resistance to chemotherapy. High ALDH activity is associated with poor prognosis in several cancers.
• Neurological Disorders: Mutations in ALDH genes can lead to neurological disorders such as Sjögren-Larsson syndrome (ALDH3A2 mutation) and pyridoxine-dependent epilepsy (ALDH7A1 mutation).
• Cardiovascular Diseases: ALDH2 has a protective role against cardiovascular diseases by reducing oxidative stress and preventing endothelial dysfunction.

Summary:

The ALDH family of enzymes plays a pivotal role in detoxifying aldehydes, maintaining cellular homeostasis, and protecting against oxidative stress. These enzymes are involved in critical metabolic pathways, including alcohol metabolism, retinoic acid synthesis, and neurotransmitter degradation. Clinical implications of ALDH function and dysfunction are significant, ranging from alcohol intolerance and cancer to neurological and cardiovascular disorders. Understanding the diverse roles of ALDHs can lead to improved therapeutic strategies for these conditions.