Evidence for an UDP-glucuronic acid/phenol glucuronide antiport in rat liver microsomal vesicles.
The transport of glucuronides synthesized in the luminal compartment of the endoplasmic reticulum by UDP-glucuronosyltransferase isoenzymes was studied in rat liver microsomal vesicles. Microsomal vesicles were loaded with p-nitrophenol glucuronide (5 mM), phenolphthalein glucuronide or UDP-glucuronic acid, by a freeze-thawing method. In was shown that: (i) the loading procedure resulted in millimolar intravesicular concentrations of the different loading compounds; (ii) addition of UDP-glucuronic acid (5 mM) to the vesicles released both intravesicular glucuronides within 1 min; (iii) glucuronides stimulated the release of UDP-glucuronic acid from UDP acid-loaded microsomal vesicles; (iv) trans-stimulation of UDP-glucuronic acid entry by loading of microsomal vesicles with p-nitrophenol glucuronide, phenolphthalein glucuronide, UDP-glucuronic acid and UDP-N-acetyl-glucosamine almost completely abolished the latency of UDP-glucuronosyltransferase, although mannose 6-phosphatase latency remained unaltered; (v) the loading compounds by themselves did not stimulate UDP-glucuronosyltransferase activity. This study indicates that glucuronides synthesized in the lumen of endoplasmic reticulum can leave by an antiport, which concurrently transports USP-glucuronic acid into the lumen of the endoplasmic reticulum.
Bánhegyi
G
G
1st Institute of Biochemistry, Semmelweis Medical University, Budapest, Hungary.
Braun
L
L
Marcolongo
P
P
Csala
M
M
Fulceri
R
R
Mandl
J
J
Benedetti
A
A
D000818:Animals; D001692:Biological Transport; D005965:Glucuronates / Q000493:pharmacokinetics*; D014453:Glucuronosyltransferase / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009596:Nitrophenols / Q000493:pharmacokinetics*; D010635:Phenolphthaleins / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014535:Uridine Diphosphate Glucuronic Acid / Q000493:pharmacokinetics*
D005965:Glucuronates; D009596:Nitrophenols; D010635:Phenolphthaleins; C049288:p-nitrophenol glucuronide; C016651:phenolphthalein glucuronide; D014535:Uridine Diphosphate Glucuronic Acid; D014453:Glucuronosyltransferase