Absorption - Pesticide Biotransformation and Disposition - page 29

across the intestine, especially when there is coexposure to other drugs or pesticides
that may compete with the pesticide of interest and consequently increase pesticide
uptake across the GI tract ( Alvinerie et al., 2008 ).

Protein (Macromolecular) Binding
Blood consists of red blood cells, white blood cells, and platelets suspended in plasma.
Plasma, which comprises approximately 55% of the blood volume in humans, also
contains a number of proteins, ions, and inorganic molecules. Many xenobiotics in
blood are reversibly bound to plasma proteins, including albumin, α 1 -acid glycopro-
tein, lipoproteins, and globulins. Reversible binding to plasma proteins enhances the
solubility of lipophilic compounds in blood and influences the rate of distribution to
tissues. Proteins are amphoteric in nature and therefore possess cationic and anionic
regions. Many acidic chemicals bind to albumin, whereas basic chemicals tend to bind
to α 1 -acid glycoprotein and lipoproteins. The high molecular weight of proteins pre-
vents them, and any toxicants they bind, from crossing cell membranes. Only the free
(or unbound) chemical is available to cross plasma membranes ( Figure 3.3 ). The inter-
action of chemicals and plasma proteins, however, is rapid and reversible. Equilibrium
is quickly established between the bound and the unbound forms of the chemical. As
an unbound chemical crosses a plasma membrane in a microenvironment, a bound
chemical dissociates to re-establish equilibrium with the unbound fraction.
Gomez-Catalan et al. (1991) investigated the distribution of various organochlorines
in rat and human blood. In rat blood, 87% of hexachlorobenzene was associated with red
blood cells, approximately 84% of DDE 1,1-dichloro-2,2-bis(chlorophenyl)ethylene was
bound to plasma proteins, lindane was nearly equally distributed between red blood cells

Blood

Tissue

Bound Bound

Free Free

Figure 3.3 Equilibrium is established between free (unbound) and bound xenobiotics in blood and
between free xenobiotics in blood and tissues. Only the free xenobiotic crosses the plasma mem-
brane, which is represented by the dashed line separating the blood and tissue compartments.