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Related Concept Videos

Drug Metabolism: Phase I Reactions01:17

Drug Metabolism: Phase I Reactions

A phase I reaction is a biochemical process that introduces a functionally reactive polar group to a substance. This transformation predominantly occurs in the liver, facilitated by the cytochrome P450 system of hemoproteins situated in the lipophilic endoplasmic reticulum of cells. The metabolite generated through this process can have varying polarities. If it is sufficiently polar, it can be easily excreted in the urine due to its water compatibility. However, if the metabolite is nonpolar,...
Phase I Oxidative Reactions: Overview01:19

Phase I Oxidative Reactions: Overview

Phase I biotransformation, or functionalization, is a crucial chemical process that converts drugs and other xenobiotics into more water-soluble forms, facilitating expulsion from the body. It involves oxidative, reductive, and hydrolytic reactions that add or unveil polar functional groups on lipophilic substrates. Key players in phase I reactions are the mixed-function oxidases. Situated in liver cell microsomes, these enzymes predominantly carry out drug metabolism. They require molecular...
Drug Metabolism: Phase II Reactions01:14

Drug Metabolism: Phase II Reactions

Phase II reactions are essential for the detoxification and elimination of drugs from the body. These reactions involve the conjugation of parent drugs or their phase I metabolites with endogenous molecules, resulting in more hydrophilic drug conjugates. The primary conjugation reactions in this phase are sulfation and glucuronidation. Both sulfation and glucuronidation typically produce biologically inactive metabolites. However, in some cases involving prodrugs, active metabolites may be...
Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems01:19

Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems

Phase I biotransformation reactions are integral to drug metabolism, predominantly involving oxidative, reductive, and hydrolytic transformations. Chief among these are oxidative reactions, which enhance the hydrophilicity of xenobiotics and introduce polar functional groups to facilitate their elimination from the body.
Oxidation reactions are fundamental in aromatic carbon-containing systems. An example is the hydroxylation of phenobarbital, a process that transforms it into...
Phase I Reactions: Hydrolytic Reactions01:15

Phase I Reactions: Hydrolytic Reactions

Hydrolysis, a cornerstone of phase I biotransformation reactions, uses water to cleave chemical bonds. This process is pivotal in drug metabolism, generating more polar metabolites that can be easily excreted.
An important hydrolytic reaction is ester hydrolysis. Ester bonds, often found in prodrugs, are broken down, increasing the solubility of drugs like aspirin and lidocaine for more straightforward elimination. Amide hydrolysis is another critical reaction, targeting amide bonds prevalent...
Phase I Reactions: Reductive Reactions01:27

Phase I Reactions: Reductive Reactions

Phase I biotransformation reductive reactions are chemical processes that modify drugs by introducing or revealing polar functional groups via reduction. Enzymes called reductases catalyze these reactions, playing a pivotal role in drug metabolism by transforming lipophilic drugs into more polar, water-soluble metabolites for easy excretion. An essential type of reductive reaction is the carbonyl group reduction, where aldehydes and ketones are reduced to alcohols. An example is the...

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Simultaneous Measurement of Superoxide/Hydrogen Peroxide and NADH Production by Flavin-containing Mitochondrial Dehydrogenases
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Simultaneous Measurement of Superoxide/Hydrogen Peroxide and NADH Production by Flavin-containing Mitochondrial Dehydrogenases

Published on: February 24, 2018

Formaldehyde dehydrogenase: beyond phase I metabolism.

Chad M Thompson1, Rebecca Ceder, Roland C Grafström

  • 1ToxStrategies, Inc., Katy, TX 77494, USA. cthompson@toxstrategies.com

Toxicology Letters
|December 8, 2009
PubMed
Summary

Class III alcohol dehydrogenase (ADH3), also known as GSNO reductase, regulates nitrosothiol homeostasis. This enzyme plays a key role in cell signaling and thiol balance, extending beyond formaldehyde metabolism.

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Published on: May 26, 2018

Area of Science:

  • Biochemistry
  • Cellular Biology
  • Environmental Toxicology

Background:

  • Formaldehyde dehydrogenase (Class III alcohol dehydrogenase, ADH3) catalyzes the reduction of S-nitrosoglutathione (GSNO).
  • GSNO reduction by ADH3 is implicated in asthma, cardiovascular disease, and immune function.
  • While recognized in biomedical fields as GSNO reductase (GSNOR), its role in environmental toxicology is less explored.

Purpose of the Study:

  • To highlight the role of ADH3 in cell signaling via thiol homeostasis.
  • To underscore the broader functions of ADH3 beyond formaldehyde metabolism.

Main Methods:

  • Literature review and evidence synthesis.

Main Results:

  • ADH3 plays a significant role in regulating nitrosothiol homeostasis.
  • Evidence suggests ADH3 is involved in cell signaling pathways through thiol balance.
  • The enzyme's function extends beyond its known role in formaldehyde metabolism.

Conclusions:

  • ADH3 is a key regulator of thiol homeostasis and cell signaling.
  • Further investigation into ADH3's broader biological roles, particularly in environmental toxicology, is warranted.