Bke2 Biochemistry Lectures

Lecture 24: Metabolism of exogenous compounds (xenobiotica)
Reading material: Glaxo Wellcome: Drug Metabolism Guide

Abstract: Food and feed contains other substances than nutrients. Some of these xenobiotics are more or less toxic or antinutritional to animals. They are absorbed and metabolised by a common set of pathways, which are also used for drugs and steroid hormones. The aim of this metabolism is to make the substances more polar and easier to excrete and is found mainly in liver, kidney and intestine.

In a first phase, polar reactive groups are introduced into the molecule. This is often done by microsomal monoxygenases containing cytochrome P450. These reactions do not always produce less toxic substances, but can also activate e.g. putative carcinogens.

In a second phase of the metabolism (conjugation) polar endogenic substances like glucuronic acid, sulphate and glutathione are coupled to the reactive groups in the xenobiotic. The conjugated substances can then actively be excreted into the gall or urine by the liver or kidney respectively. The conjugates excreted through the gall may be cleaved by micro-organisms in the intestine and reabsorbed. This is known as the enterohepatic circulation.

Xenobiotics in the diet can induce and thus increase the activity of the drug metabolising enzymes. This will influence the metabolism of other substances, drugs, carcinogens and toxins. They will be more or less toxic/active depending on which enzymes are affected. Anticarcinogens in the diet often work through this action.

The xenobiotic-metabolising systems are similar in animals, but may partly vary with species, strains, sex and age.

Key concepts:
Xenobiotic metabolism
Uptake and elimination of xenobiotics
Microsomal monooxygenases
Cytochrome P450
Conjugation
Enterohepatic circulation
Induction of drug metabolism
Diet effects on drug metabolism

Links:

Lecture index

[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35]