Phospholipids and UDP-glucuronosyltransferase. Structure/function relationships.

Abstract

The activation of delipidated microsomal UDP-glucuronosyltransferase from pig liver (GT2P type of enzyme) was studied as a function of several structural modifications of 1-palmitoyl-sn-glycero-3-phosphocholine, which is known to be a good activator of the enzyme. The following types of compounds were tested: substitution of H for OH at position 2; substitution of an ether for an acyl link at position 1; variation of the phosphorus-nitrogen or acyl ester-phosphate ester distances; removal of the glycerol backbone; optical isomers; and substitution of phosphoethanolamine for phosphocholine. Although there were variations in the extent to which these compounds activated delipidated enzyme, all the above types of lipids were effective in this regard. By contrast, lipids with a net negative charge did not activate the enzyme. They inhibited it reversibly. Positively charged lipids, even those lacking a phosphate group, were effective activators. These results indicate that GT2P is unlikely to interact with specific chemical groups of its phospholipid milieu. Effective activation appears instead to depend on the physical properties of the lipid environment