12 Questions
What is the main purpose of biotransformation in the body?
To change toxicants to hydrophilic molecules for elimination
What is a key characteristic of the resulting metabolites after biotransformation?
They are usually more hydrophilic than the original toxicant
How does the hydrophilic nature of biotransformed metabolites affect their distribution in the body?
It decreases their ability to cross membranes
What is the property of xenobiotics that enables them to penetrate lipid membranes?
Lipophilicity
During phase I metabolism of xenobiotics, what is typically introduced into the molecule?
A polar group
What is the most important effect of introducing a polar group into a xenobiotic molecule during phase I metabolism?
To render it a suitable substrate for phase II reactions
In phase II reactions, what type of reactions are referred to as conjugation reactions?
Glucuronidation reactions
Which enzyme system is most important in catalyzing phase I biotransformation reactions?
Cytochrome P-450
What is the purpose of adding a small polar group to a toxicant during phase I biotransformation reactions?
To increase elimination
Which part of the body has the highest capacity for biotransformation?
Liver
What role do microbes living in the intestine play in biotransformation?
They play a role equal to that of the liver
What is the primary function of phase II reactions in biotransformation?
Conjugate a molecule making it more water-soluble
Study Notes
Biotransformation
- Biotransformation is a process that alters compounds to produce water-soluble conjugation products that are readily excreted.
- It is a detoxication mechanism, but in some cases, the intermediates or final products can be more toxic than the parent compound, resulting in an activation or intoxication mechanism.
Tissue Capacity for Biotransformation
- Skin, testes, and placenta have a low capacity for biotransformation.
- Intestines, kidneys, and lungs have a medium capacity.
- The liver has the highest capacity for biotransformation.
Liver's Role in Biotransformation
- The liver receives blood directly from the gastrointestinal tract, allowing for immediate detoxication.
- The "first-pass" effect shunts blood from the gastrointestinal tract to the liver via the portal vein, increasing the possibility of immediate detoxication.
Subcellular Level of Biotransformation
- Enzymes that catalyze biotransformation reactions occur free in the cytoplasm or bound to the membrane of the endoplasmic reticulum in hepatocytes and other cells.
- Microsomal enzymes are associated with phase I reactions.
- Cytosolic enzymes are associated with phase II reactions.
Microbial Role in Biotransformation
- Microbes living in the intestine are capable of biotransformation, with a role likely equal to that of the liver.
Factors Affecting Biotransformation
- Age, gender, nutrition, disease, and time of day can affect biotransformation.
- Nutritional status and disease can impair an individual's capacity to biotransform xenobiotics.
Phase I Reactions
- Phase I reactions add a small polar group to the toxicant, enhancing its solubility in water.
- Reactions are catalyzed by nonspecific enzyme systems, primarily cytochrome P-450.
- Phase I reactions involve oxidation, reduction, or hydrolysis.
Phase II Reactions
- Phase II reactions, also known as conjugation reactions, add a molecule provided by the body to the reactive site produced during phase I.
- Conjugation reactions produce a water-soluble conjugate metabolite that can be readily eliminated from the body.
Glucuronidation
- Glucuronidation is the process of adding glucuronide to the toxicant or phase I metabolite, primarily occurring in hepatocytes.
- Glucuronidation increases the hydrophilicity of the metabolite, facilitating elimination from the body.
Explore the process of biotransformation where substances are transformed into hydrophilic molecules for elimination from the body. Learn how this process results in chemically distinct metabolites and facilitates the excretion of toxicants.
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