Alcohol sulfotransferase

Alcohol Sulfotransferase (AST) is an enzyme that plays a crucial role in the metabolism of various alcohols and steroids by catalyzing the sulfonation process. This enzyme is part of the sulfotransferase (SULT) family, which is involved in the phase II metabolism of drugs and endogenous compounds, making them more soluble and easier to excrete from the body. Alcohol sulfotransferase specifically transfers a sulfo group (SO3) from a donor molecule, 3'-phosphoadenosine 5'-phosphosulfate (PAPS), to an acceptor alcohol, forming a sulfonated alcohol product.

Function

The primary function of alcohol sulfotransferase is to facilitate the detoxification and excretion of potentially harmful compounds. By sulfonating alcohols and steroids, AST increases their solubility in water, enabling their easier removal from the body through urine. This process is vital for the metabolism of various drugs, environmental chemicals, and endogenous compounds, including hormones and neurotransmitters.

Structure

Alcohol sulfotransferase is a protein that can exist in multiple isoforms, each encoded by different genes within the human genome. These isoforms vary in their tissue distribution and substrate specificity, allowing for a wide range of compounds to be sulfonated. The structure of AST typically includes a binding site for the PAPS molecule and a separate binding site for the acceptor alcohol.

Clinical Significance

Alterations in the activity of alcohol sulfotransferase can have significant clinical implications. For example, variations in AST activity can affect an individual's response to drugs, susceptibility to toxicity from environmental chemicals, and the metabolism of endogenous hormones. Certain genetic polymorphisms in the genes encoding AST isoforms have been linked to diseases such as cancer, due to their role in the metabolism of carcinogens, and to hormonal disorders, due to their involvement in the regulation of hormone levels.

Pharmacology

Understanding the activity of alcohol sulfotransferase is important in pharmacology for the development of drugs and in predicting drug interactions. Inhibitors of AST can increase the half-life of drugs that are substrates of this enzyme, potentially leading to toxicity. Conversely, inducers of AST can decrease the effectiveness of these drugs by increasing their rate of metabolism.

Research

Research into alcohol sulfotransferase continues to uncover its roles in health and disease. Studies are focused on identifying new substrates of AST, understanding the genetic basis of its activity, and exploring its involvement in disease processes. This research has the potential to lead to new therapeutic targets and strategies for the treatment of diseases related to altered sulfonation.