Language
Country/Area
No result found
Enzyme activity revealed: What is the role of aldehyde dehydrogenase in cancer development?
Aldehyde dehydrogenases (ALDH) are a group of enzymes that catalyze the oxidation of aldehydes and play important roles in many biological processes, especially in the development of cancer. Scientists have identified nineteen ALDH genes in the human genome. These genes are involved in the detoxification process of aldehydes, including the degradation of exogenous and endogenous aldehydes. Especially ALDH2 and ALDH1, which are inseparable from the oxidation of aldehydes and have important physiological functions in many tissues.
Aldehyde dehydrogenase is a polymorphic enzyme responsible for converting aldehydes into carboxylic acids and has a decisive influence on metabolic processes.
Structure and function of aldehyde dehydrogenase
In mammals, aldehyde dehydrogenases are divided into three different categories: category 1 (low Km, intracytoplasmic), category 2 (low Km, within mitochondria), and category 3 (high Km, Mainly expressed in tumors, stomach and cornea). All three categories have constitutive and inductive forms. Among them, ALDH1 and ALDH2 are the most important enzymes for aldehyde oxidation, and both are tetramers composed of 54 kDa subunits.
Active site and mechanism
The active site of aldehyde dehydrogenase is basically conserved among different enzymes. Although the number of amino acids in the subunit may change, its function remains basically unchanged. The active site can bind an aldehyde molecule and an NAD+ or NADP+ molecule, which act as cofactors. Studies have shown that cystine and glutamate molecules in the active site interact with aldehyde substrates.
In this NAD(P)+-dependent reaction, aldehydes enter the active site of the enzyme and are converted into carboxylic acids through a series of chemical reactions.
The mechanism of these reactions involves multiple steps, in which the carbon-hydrogen bond of the aldehyde molecule releases hydrogen protons to form NAD(P)H, and then water molecules further participate in the catalytic reaction to promote the production of products.
Deletion and pathology of aldehyde dehydrogenase
ALDH2 plays a key role in the oxidation of alcohol, helping to maintain low levels of acetaldehyde in the blood. When the activity of ALDH2 is insufficient, the concentration of acetaldehyde in the blood will increase, causing symptoms of "alcohol flush reaction" such as facial flushing, heart palpitations, and nausea. This is also known as "Asian flush syndrome."
The mutated form of ALDH2, ALDH2*2, is quite common in regions such as Japan and Taiwan, and is associated with a variety of cancers, including esophageal cancer, throat cancer, etc.
Research shows that mutations in ALDH2 lead to slower clearance of acetaldehyde, which may explain why these areas have lower rates of alcohol addiction. This phenomenon also makes ALDH2 mutations closely associated with increased cancer risk.
Relationship between aldehyde dehydrogenase and other diseases
In addition, ALDH expression is associated with various neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. Studies have found that patients with these diseases have significantly reduced gene expression and enzyme activity, which may be related to aldehydes derived from toxic lipid oxidation.
Inhibition of aldehyde dehydrogenase is thought to be one of the pathogenic mechanisms leading to Parkinson's disease, further emphasizing the physiological importance of this enzyme.
Research has pointed out that mouse models lacking ALDH exhibit motor performance degradation and aging-related memory deficits similar to Parkinson's disease. These phenomena provide a new perspective for understanding neuropathy.
Summary and future prospects
Aldehyde dehydrogenase plays an irreplaceable role in the organism, and its role in aldehyde oxidation and anti-cancer theory is gradually being discussed in depth. Understanding the importance of these enzymes in fighting cancer, alcohol metabolism, and neurodegenerative diseases may provide new ideas for future treatments. As the research on ALDH continues to deepen, we cannot help but ask: What other mysteries of life can these enzymes reveal to us?
