Environmental Toxicology Diary

What is metabolism?
How does the toxicant biotransformed?
What are factors affecting metabolism?

What is metabolism?
Metabolism or often referred to biotransformation is a process which result in changing in the chemical structure of the toxic substance. These changes in a variety of tissue such as liver, kidney, lung, skin and GI tract as well. Primary spot for biotransformation is in liver.

How does the toxicant biotransformed?
The transformation process take place because of the interaction of the toxic substance with enzymes in the cell endoplasmic reticulum, cytoplasm and mitochondria. Interaction with these enzymes may change the toxicant to either a less or a more toxic form. It also can change chemical nature of the toxicant from a water-insoluble to a water-soluble chemical that can be excreted by the kidneys. Additionally, the biotransformation can result in the production of chemical intermediates that are more toxic than the original chemical.

Usually, biotransformation occurs in two phases. Phase I involves catabolic reaction, this break down the toxicant into various components. Catabolic include oxidation, reduction and hydrolisis. In most cases these reactions make the chemical less toxic, more water soluble and easier to excrete.

Phase II involves the binding of molecules to either the original toxic molecule or the toxic molecule metabolite derived from phase I reactions. The final product is usually water soluble, thus easier to excrete from the body. Phase II include glucuronidation, sulfation, acetylation, methylation, conjugation with glutathione and conjugation with amino acids (glycine, taurine and glutamic acid).

These phases may occur simultaneously or sequentially by producing single or more intermediates. Intermediates may or may not be more toxic than the parent compound, the effect is dependent on how rapidly the intermediate undergoes further metabolism to less toxic substances, how much of it is produced and accumulated in cells, what type of cellular damage is caused by the toxic intermediate and what factors may effect excretion of the toxic material.

What are factors affecting metabolism?
The rate at which metabolism of toxic substances occurs is dependent on a variety of factor that can be categrized into two groups: factors that affect the metabolic processes directly and factors that affect the transport of toxic substance to tissues where metabolism occurs.

Factors that affecting metabolism are also some of the same factors affecting biotransformation, since the rate of transformation is in part directly related to the toxic effects. Biotransformation is affected by the species of the test animal, age, sex, disease, nutritional status, enzyme induction or inhibition and genetics. Newborn babies are more susceptible to a variety of chemicals such as pesticides because the cytochrome P-450 enzymes, that important for pesticide detoxification reactions, are not well developed, which cause biotransformation and detoxification does not occur readily.

Toxic substances must be transported to the appropriate tissues in order for metabolism to occur. Factors such as absorption rate, perfusion rate, plasma protein binding and storage will affect the rate at which a toxic substance is delivered to the tissue where metabolism occurs. Lipid-insoluble substances with large molecular weights will not be delivered as rapidly to active metabolic sites such as the liver.

Reference:
Kent, C. 1998. Basics of Toxicology. John Wiley & Sons, Inc. New York

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