The digestion of phospholipids is carried out by phospholipases, primarily phospholipase A 2 (EC ). The enzyme is present in the pancreatic juice in the form of a zymogen, called prophospholipases A 2 , and is activated by trypsin in the intestinal lumen. It catalyzes specifically the cleavage of the fatty acid at the sn -2 position of the phospholipids, whereas it has a broad specificity with respect to both the length of the carbon chain of the target fatty acid and the polar head groups of the phospholipids.
As previously seen, most of the phospholipids in the intestinal lumen are of biliary origin, and only a small fraction derives from diet. In the bile, phospholipids form micelles with cholesterol and bile salts, and in the intestinal lumen they are distributed between the lipid droplets and these micelles, with a preference for the latter. And in the micelles, phospholipids, mostly phosphatidylcholine, act as a substrate. In the case of phosphatidylcholine, a free fatty acid and lysophosphatidylcholine (a lysophospholipid) are the reaction products.
In pancreatic juice, it is present phospholipase A 1 as well, which removes the fatty acid at the sn -1 position of the phospholipid.
In the intestinal mucosa, there seems to be a third, modest, phospholipase activity, thanks to an intrinsic membrane enzyme. This enzyme is called phospholipase B or retinyl ester hydrolase, being active also on vitamin A esters.
The digestion of phospholipids can ends with the formation of a free fatty acid and a lysophospholipid or can be complete.
Both polar and non-polar substances diffuse via transcellular and intercellular routes by different mechanisms. The polar molecules mainly diffuse through the polar pathway consisting of “bound water” within the hydrated stratum corneum whereas the non-polar molecules dissolve and diffuse through the non-aqueous lipid matrix of the stratum corneum . Thus the principal pathway taken by a penetrant is decided mainly by the partition coefficient (log K). Hydrophilic drugs partition preferentially into the intracellular domains, whereas lipophillic permeants (octanol/water log K > 2) traverse the stratum corneum via the intercellular route. Most molecules pass the stratum corneum by both routes. 5