The influence of charge and the distribution of charge in the polar region of phospholipids on the activity of UDP-glucuronosyltransferase.

摘要: Abstract Studies of the mechanism lipid-induced regulation microsomal enzyme UDP-glucuronosyltransferase have been extended by examining influence charge within polar region on ability lipids to activate delipidated pure enzyme. The effects net negative charge, separation in phosphocholine, and distribution were studied using GT2p isoform isolated from pig liver. Prior experiments shown that with inhibit (Zakim, D., Cantor, M., Eibl, H. (1988) J. Biol. Chem. 263, 5164-5169). current show extent inhibition a molar basis increases as -1 -2. inhibitory effect negatively charged is functional state not due electrostatic repulsion substrates Although removed when balanced positive quaternary nitrogen, neutrality sufficient condition for activation In addition balance between Pi distance charges orientation dipole created them are critical GT2p. must be separated equivalent three -CH2- groups optimal lipid. Shortening this one unit leads lipid ineffective activating Reversal which polymethylene side lipid-water interface extends into water also produces effective On other hand, phosphoserine region, has "normal" P-N but carries do This result again illustrates importance phosphocholine modulating