ALDH1, or Aldehyde Dehydrogenase 1, is an important enzyme found throughout the human body. This enzyme plays a considerable part in maintaining cellular well-being and physiological balance. Its functions extend across various biological processes, demonstrating its widespread significance. Understanding ALDH1 provides insight into how the body manages its internal environment.
What is ALDH1?
ALDH1 belongs to the aldehyde dehydrogenase (ALDH) superfamily, enzymes responsible for oxidizing aldehydes. ALDH1 is a cytosolic enzyme, operating within the fluid portion of cells. The human genome contains 19 identified ALDH genes, with ALDH1 having three main isotypes: ALDH1A1, ALDH1A2, and ALDH1A3. These enzymes convert aldehydes into less reactive carboxylic acids by using NAD(P)+ as a co-factor. ALDH1 enzymes are present in various tissues, with higher concentrations in organs like the liver, and their widespread distribution highlights their involvement in numerous biological activities.
ALDH1’s Role in Detoxification
ALDH1 plays a role in protecting cells from harmful substances by breaking down toxic aldehydes. These aldehydes are often byproducts of normal metabolic processes, such as lipid peroxidation, which damages cellular components. Aldehydes can also originate from external sources, including environmental pollutants and certain medications. ALDH1 converts these reactive aldehydes into harmless carboxylic acids, preventing them from causing cellular damage, DNA alterations, or disruptions to signaling pathways. This detoxification process helps maintain cellular homeostasis and supports cell function.
ALDH1 in Stem Cells and Disease
ALDH1 activity is used as a marker for both normal stem cell populations and cancer stem cells, helping identify these cell types which possess self-renewal and differentiation capabilities. ALDH1A1 is an ALDH isozyme linked to stem cell populations. The enzyme’s role in cancer is complex, as elevated ALDH1 levels are observed in various solid tumors, including breast, lung, and liver cancers. This overexpression can contribute to cancer progression, drug resistance, and metastasis. ALDH1 protects cancer cells by detoxifying harmful aldehydes produced during chemotherapy, thereby reducing oxidative stress and promoting cell survival.
ALDH1 and Alcohol Processing
ALDH enzymes, including ALDH1, are involved in the metabolism of alcohol; when alcohol (ethanol) is consumed, it is first converted into acetaldehyde, a toxic compound, by alcohol dehydrogenase (ADH) enzymes. ALDH enzymes then break down acetaldehyde into acetate, a less harmful substance. While ALDH2 is largely responsible for acetaldehyde metabolism, ALDH1 (specifically ALDH1A1) also contributes to this process. Genetic variations in ALDH enzymes, particularly the ALDH22 variant, can result in an inactive enzyme, leading to acetaldehyde accumulation. This buildup causes unpleasant symptoms like facial flushing, rapid heartbeat, and nausea, often referred to as “alcohol flush syndrome”.