Factors affecting transport and absorption
Toxic substances must be transported to the appropriate tissues in order for metabolism to occur. Many of the factors discussed earlier in this chapter 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. In general, organic substances-because of their high lipid solubility-are easily absorbed and undergo metabolism. Lipid-insoluble substances with large molecular weights will not be delivered as rapidly to active metabolic sites such as the liver.
The perfusion rate of a given tissue is important in determining how quickly a toxic substance will be transformed. Organs such as the liver and kidneys have a high perfusion rate relative to other tissue types. These organs have the potential to extract and detoxify larger quantities of toxicants from the blood. Tissues with low perfusion rate-such as fats-generally have low metabolic rates. Any toxic substances absorbed in these types of tissues are metabolized slowly and accumulate over time.
Protein binding can serve a dual purpose relative to metabolism of toxic substances. Toxic substances bound to proteins in the blood do not easily move across cell membranes. In many cases this slows the rate at which the toxicant is metabolized because the substance may not be readily absorbed by the tissue where detoxification occurs. Binding to intracellular protein provides an efficient involved in metabolism. The large size of the protein-bound molecules slows their removal from the cell.