[Phospholipid composition of the hepatic microsomal membrane and its relationship to bilirubin UDP glucuronyltransferase in human cholestasis].
A number of morphological and functional changes on liver cells were reported during experimental cholestasis. Some specific metabolic pathways catalyzed by "membrane bound" enzymes were described to be altered by lipid microenvironment changes. The purpose of he present study is to establish Bilirubin UDP-Glucuronyltransferase activity--a microsomal integral enzyme responsible for bilirubin conjugation--and microsomal phospholipid profile in cholestatic and normal patients. Surgical liver biopsies were taken fron five patients suffering prolonged extrahepatic cholestasis, and five patients submitted to abdominal surgery excluding hepato-biliary diseases that were considered as controls. The following biochemical parameters were determined in both groups: bilirubin concentration, alkaline phosphatase, gamma-glutamyltranspeptidase, oxalacetic and pyruvic transaminases, and pseudo-cholinesterase activities. Serum cholestatic markers showed significative increments in cholestatic patients (Table 1). Total Bilirubin UDP-Glucuronyltransferase activity was similar comparing normal and cholestatic individuals (1.11 +/- 0.66 and 1.93 +/- 0.82 nmol conjugated bilirubin/mg protein in 10 min. respectively). When final reaction product was analysed, the normal group showed 80% of bilirubin diglucuronide; but resulted undetectable in cholestatic patients yielding 100% of bilirubin monoglucuronide. Microsomal phospholipid analysis showed a decrease in phosphatidylcholine and phosphatidylethanolamine contents in the cholestatic group; probably due to the action of bile acids accumulated into the hepatic cells. Simultaneously we found an increment in phosphatidylserine and sphingomyelin levels in cholestatic patients compared to normals (Figure 1). This fact could be explained by the existence of special sites in the membrane for the latter phospholipids, protected against bile acids detersive action.(ABSTRACT TRUNCATED AT 250 WORDS)
Bengochea
L
L
Cátedra de Fisiopatología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Ouviña
G
G
Pavese
A
A
Carbone
A M
AM
Lemberg
A
A
D000368:Aged; D001663:Bilirubin / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology; D001651:Cholestasis, Extrahepatic / Q000378:metabolism*; D005260:Female; D014453:Glucuronosyltransferase / Q000378:metabolism; D006801:Humans; D008297:Male; D008862:Microsomes, Liver / Q000737:chemistry*; D008875:Middle Aged; D010743:Phospholipids / Q000032:analysis*
D010743:Phospholipids; D014453:Glucuronosyltransferase; D001663:Bilirubin
Composición fosfolipídica de la membrana microsomal hepática y su relación con la actividad de la bilirrubina UDP-glucuroniltransferasa en colestasis humana.