11.12: Biotransformation
- Page ID
- 485520
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\(\newcommand{\avec}{\mathbf a}\) \(\newcommand{\bvec}{\mathbf b}\) \(\newcommand{\cvec}{\mathbf c}\) \(\newcommand{\dvec}{\mathbf d}\) \(\newcommand{\dtil}{\widetilde{\mathbf d}}\) \(\newcommand{\evec}{\mathbf e}\) \(\newcommand{\fvec}{\mathbf f}\) \(\newcommand{\nvec}{\mathbf n}\) \(\newcommand{\pvec}{\mathbf p}\) \(\newcommand{\qvec}{\mathbf q}\) \(\newcommand{\svec}{\mathbf s}\) \(\newcommand{\tvec}{\mathbf t}\) \(\newcommand{\uvec}{\mathbf u}\) \(\newcommand{\vvec}{\mathbf v}\) \(\newcommand{\wvec}{\mathbf w}\) \(\newcommand{\xvec}{\mathbf x}\) \(\newcommand{\yvec}{\mathbf y}\) \(\newcommand{\zvec}{\mathbf z}\) \(\newcommand{\rvec}{\mathbf r}\) \(\newcommand{\mvec}{\mathbf m}\) \(\newcommand{\zerovec}{\mathbf 0}\) \(\newcommand{\onevec}{\mathbf 1}\) \(\newcommand{\real}{\mathbb R}\) \(\newcommand{\twovec}[2]{\left[\begin{array}{r}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\ctwovec}[2]{\left[\begin{array}{c}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\threevec}[3]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\cthreevec}[3]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\fourvec}[4]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\cfourvec}[4]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\fivevec}[5]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\cfivevec}[5]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\mattwo}[4]{\left[\begin{array}{rr}#1 \amp #2 \\ #3 \amp #4 \\ \end{array}\right]}\) \(\newcommand{\laspan}[1]{\text{Span}\{#1\}}\) \(\newcommand{\bcal}{\cal B}\) \(\newcommand{\ccal}{\cal C}\) \(\newcommand{\scal}{\cal S}\) \(\newcommand{\wcal}{\cal W}\) \(\newcommand{\ecal}{\cal E}\) \(\newcommand{\coords}[2]{\left\{#1\right\}_{#2}}\) \(\newcommand{\gray}[1]{\color{gray}{#1}}\) \(\newcommand{\lgray}[1]{\color{lightgray}{#1}}\) \(\newcommand{\rank}{\operatorname{rank}}\) \(\newcommand{\row}{\text{Row}}\) \(\newcommand{\col}{\text{Col}}\) \(\renewcommand{\row}{\text{Row}}\) \(\newcommand{\nul}{\text{Nul}}\) \(\newcommand{\var}{\text{Var}}\) \(\newcommand{\corr}{\text{corr}}\) \(\newcommand{\len}[1]{\left|#1\right|}\) \(\newcommand{\bbar}{\overline{\bvec}}\) \(\newcommand{\bhat}{\widehat{\bvec}}\) \(\newcommand{\bperp}{\bvec^\perp}\) \(\newcommand{\xhat}{\widehat{\xvec}}\) \(\newcommand{\vhat}{\widehat{\vvec}}\) \(\newcommand{\uhat}{\widehat{\uvec}}\) \(\newcommand{\what}{\widehat{\wvec}}\) \(\newcommand{\Sighat}{\widehat{\Sigma}}\) \(\newcommand{\lt}{<}\) \(\newcommand{\gt}{>}\) \(\newcommand{\amp}{&}\) \(\definecolor{fillinmathshade}{gray}{0.9}\)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.