Phase II Reactions
What is phase II reactions?
What are types of phase II reactions?
What is phase II reactions?
During phase II reactions, the toxic substances or its metabolite is bound with a compound that generally renders the newly synthesized molecule less toxic. This type of reaction is referred to as conjugation. Conjugation is the joining of two substances to form a single molecule, which can increase water solubility and excretion. One of the most important conjugation is conjugation with glucuronidation.
What are types of phase II reactions?
There are conjugation with glucuronidation, conjugation with glutathione, sulfation, acetylation and methylation.
Conjugation with glucuronidation occurs as a result of the conjugation of glucuronic acid with either a metabolite from phase I reactions or with the parent compound. There are several compoinds that interact with glucuronic acid, which are alcohols (R-OH), carboxylic acid (R-COOH), sulfhydryl compounds (R-SH) and amines (R-NH2). It can also be conjugated with organophosphate pesticides and organic solvents such as benzene. The molecules are more water soluble and excreted by the kidneys.
Conjugation with glutathione is an important Phase II reaction that renders highly toxic metabolites harmless. Chemical intermediates of some toxic substances cause cellular damage and genetic mutations as a result of binding with nucleic acids. Conjugation of these intermediates with glutathione prevents binding with the nucleic acids, therefore preventing the occurence of mutation. Metabolites of organics such as benzene, chloroform and carbon tetrachloride are conjugated with glutathione.
Sulfation involves the conjugation of a sulfate group with the toxic substance molecule or its metabolite. Substances that do not undergo Phase I reactions can also undergo sulfation.
Methylation is the addition of one or more methyl groups to a toxic molecule. Methylation and some degree of acetylation decrease water solubility. Toxicant that undergo these reactions are retained in the body for longer periods of time. Metals such as mercury can undergo methylation to be methyl mercury, highly toxic, soluble in lipids and concentrates in neural tissue, where it may affect the structure and function of nerve cells. Nicotine, arsenic and selenium can undergo methylation while aromatic amines are primarily biotransformed by acetylation. Acetylation can either activate or deactivate te aromatic amines. Activated amines can react with sensitive intracellular molecules -such as DNA- causing mutations and disrupting normal cellular function. They may also interact with structural and functional proteins (enzymes).
Reference:
Kent, C. 1998. Basics of Toxicology. John Wiley & Sons, Inc. New York
