Oral Bioavailability - Dealing with Contaminated Sites: From Theory Towards Practical Application - page 292

Inorganic contaminants

Organic contaminants

Adsorption / clay, organic matter
Binding to chelates
pH / ionised forms
Speciation

Adsorption / organic matter, clay
Log Kow, log Koc
Cluster

Biliary acids complex

Affinity to receptor
Competition
between cations

Stationary aqueous layer

P-gp

Apical membrane

Epithelial
cell

Metabolism
CYP 450

Metabolic susceptibility
Log Kow

Binding proteins

metallothionein

Active transport

Passive diffusion
Arrow thickness is
proportional to flow

Basal membrane

Fig. 7.4 Mechanisms of absorption

(Oomen 2000 )) in conjunction with a heterogeneous mass of other cell types such
as goblet cells (those that secrete mucin) and endocrine cells populate the surface of
each villi.
Because of the different properties of nutrients/contaminants, absorption can
occur either by the para or trans cellular route, as shown in Fig. 7.4 . Figure 7.4
shows that the epithelial cells bound together at their luminal facing ends by special-
ized facings known as 'zonnulae occludens', which carry out a number of functions
such as the preservation of the cell sheet integrity and the formation of a bound-
ary between apical surfaces and basolateral membranes. For the transcellular route,
movement occurs across both apical and basolateral membranes of the intestinal
lumen, however for the para cellular route movement of nutrients/contaminants
occurs by circumventing these membranes. The small spaces between the cells mean
that paracellular absorption can only occur for the transport of small hydrophobic
molecules. Passive forces drive this process, with the rate limiting forces which
determine the extent or magnitude of transport determined by the permeability
between the cells. Larger molecules are transported by the transcellular route, which
involves the movement across both the apical and basolateral membranes. The
accepted model for transcellular transport assumes that substances absorbed by this
route enter the cell across the apical and leave via the basolateral membrane and that
the opposite is true for secretions. The mechanisms of transcellular transport may
occur by:

• Transport by a specific carrier, either active or facilitated. Active transport is the

mechanism by which proteins (after transformation into amino acids or small