ALDH1A1

ALDH1A1 (Aldehyde Dehydrogenase 1 Family, Member A1) is a gene in humans that encodes for an isoform of aldehyde dehydrogenase. This enzyme is a cytosolic NAD+-dependent enzyme responsible for oxidizing a wide variety of aliphatic and aromatic aldehydes. It plays a crucial role in the detoxification of aldehydes generated by alcohol metabolism and lipid peroxidation, as well as in the metabolism of retinal (vitamin A) to retinoic acid, a key signaling molecule important in cell growth, differentiation, and development.

Function:

The primary function of ALDH1A1 is the oxidation of aldehydes to carboxylic acids. This is a vital process in several metabolic pathways. Its involvement in retinoic acid synthesis is particularly important, as retinoic acid regulates gene expression through binding to nuclear receptors and influencing cell behavior. The enzyme's activity is also important in protecting cells from the toxic effects of aldehydes, which can damage DNA and other cellular components.

Gene and Protein:

The ALDH1A1 gene is located on chromosome 9q21.13. The protein produced by this gene is a homotetramer, meaning it is composed of four identical subunits. Each subunit contains an active site where aldehydes are oxidized.

Clinical Significance:

ALDH1A1 has been implicated in a variety of diseases, including cancer. In some cancers, ALDH1A1 is overexpressed and is considered a marker for cancer stem cells, which are a subpopulation of tumor cells that possess the ability to self-renew and differentiate, contributing to tumor growth and metastasis. Conversely, in other cancers, loss of ALDH1A1 expression has been associated with increased susceptibility to chemotherapy. Genetic variations in the ALDH1A1 gene can also affect an individual's susceptibility to alcohol-related disorders. Some studies have linked ALDH1A1 polymorphisms to an increased risk of certain birth defects.

Related Enzymes:

The ALDH superfamily encompasses a broad range of aldehyde dehydrogenases, each with distinct substrate specificities and tissue distributions. Other notable ALDH family members include ALDH2, which is primarily involved in alcohol metabolism in the mitochondria, and ALDH3A1, which is found in the cornea and other tissues.