Section 12: Biotransformation
- Page ID
- 316745
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Learning Objectives
After completing this lesson, you will be able to:
- Explain biotransformation, including its importance to survival and the body sites it involves.
- Define enzymes and the three types of enzyme specificity.
- Explain the two phases of biotransformation.
- Identify factors that influence the effectiveness of biotransformation.
In this section...
Topics include:
Section 12: Key Points
What We've Covered
This section made the following main points:
- Biotransformation is the process by which a substance changes from one chemical to another (transformed) by a chemical reaction within the body.
- Biotransformation is vital to survival because it transforms absorbed nutrients into substances required for normal body functions.
- Potential complications of biotransformation include:
- Detoxification — biotransformation results in metabolites of lower toxicity than the parent substance.
- Bioactivation — biotransformation results in metabolites of greater toxicity than the parent substance.
- Chemical reactions continually occur in the body to build up new tissue, tear down old tissue, convert food to energy, dispose of waste materials, and eliminate toxic xenobiotics.
- Enzymes are catalysts for nearly all biochemical reactions in the body; essential biotransformation reactions would be slowed or prevented without these enzymes, causing major health problems.
- There are generally three types of enzyme specificity:
- Enzymes with absolute specificity catalyze only one reaction.
- Enzymes with group specificity act only on molecules that have specific functional groups.
- Enzymes with linkage specificity act on a particular type of chemical bond regardless of the rest of the molecular structure.
- There are two biotransformation reaction phases:
- Phase I reactions modify the chemical by adding a functional structure, allowing the substance to "fit" into a second (Phase II) enzyme:
- Oxidation — the substrate loses electrons.
- Reduction — the substrate gains electrons.
- Hydrolysis — the addition of water splits the toxicant into two fragments or smaller molecules.
- Phase II reactions conjugate (join together) the modified xenobiotic with another substance. The most important Phase II reactions are:
- Glucuronide conjugation, a high-capacity pathway — glucuronic acid is added directly to the toxicant or its Phase I metabolite, generally resulting in hydrophilic conjugates excreted by the kidney or bile.
- Sulfate conjugation, a low-capacity pathway — decreases the toxicity of xenobiotics, resulting in highly polar sulfate conjugates readily secreted in the urine.
- Phase I reactions modify the chemical by adding a functional structure, allowing the substance to "fit" into a second (Phase II) enzyme:
- Biotransformation sites are the:
- Liver (primary site, which also makes it the most susceptible to damage by ingested toxicants).
- Kidneys (about 10-30% of the liver's capacity).
- Skin, intestines, testes, and placenta (low capacity).
- Biotransformation effectiveness depends on factors that can inhibit or induce enzymes and dose levels, including species, age, gender, genetic variability, nutrition, disease, exposure to other chemicals, and the dose level.