Serum Concentrations of Bile Acid Glucuronides in Hepatobiliary Diseases

Abstract

Bile acid glucuronides in the serum in various hepatobiliary diseases (36 cases) were quantitated by mass fragmentography and their clinical significance was discussed. Serum was added to defined amounts of deuterium-labeled bile acids and their glucuronide and sulfate derivatives, and the bile acids were separated into unconjugated, glucuronidated and sulfated groups after enzymatic cleavage of amide bonds. The liberated bile acids were quantitated by mass fragmentography. Bile acid glucuronides comprised about 7–8 % of the total bile acids in the serum of various patients. Chenodeoxycholic acid was the major glucuronidated bile acid while cholic acid was mostly unconjugated. Lithocholic acid was almost all either sulfated or glucuronidated. In patients with obstructive jaundice, glucuronidated bile acids also comprised about 5 %, although their absolute amounts were increased. In patients with liver cirrhosis, bile acid glucuronides were decreased, especially in decompensated cases, possibly as a result of hepatocellular dysfunction.

The liver X-receptor alpha controls hepatic expression of the human bile acid–glucuronidating UGT1A3 enzyme in human cells and transgenic mice

“…35 Furthermore, this observation indicates that LXR␣ may participate to the increase of circulating concentrations of CDCA-and LCA-glucuronides in cholestatic patients. 5 Indeed, 24S-hydroxycholesterol also accumulates during cholestasis 12,36 and in hepatocytes, accumulating 24S-hydroxycholesterol may activate LXR␣ which in turn would stimulate the UGT1A3-dependent glucuronidation of CDCA and LCA.…”

“…During this enterohepatic circulation, BAs undergo several metabolic alterations, including glucuronide conjugation. 3 The most abundant glucuronide conjugate reported in human plasma is CDCA-glucuronide, followed by LCA-glucuronide, 4,5 the concentrations of which are respectively increased by 50-and 30-fold in cholestatic patients. 5 BA glucuronidation allows their transport by transporters at the basolateral membrane of hepatocytes, 3 thus favoring urinary rather than biliary excretion during cholestasis.…”

“…3 The most abundant glucuronide conjugate reported in human plasma is CDCA-glucuronide, followed by LCA-glucuronide, 4,5 the concentrations of which are respectively increased by 50-and 30-fold in cholestatic patients. 5 BA glucuronidation allows their transport by transporters at the basolateral membrane of hepatocytes, 3 thus favoring urinary rather than biliary excretion during cholestasis. 3 Glucuronide conjugation results in the formation of ether-type or acyl-type glucuronides in which the glucuronosyl group is added to the 3␣-hydroxyl group or the 24-carboxyl group of the steroid nucleus of primary and secondary BAs, respectively.…”

Enhancement of Endothelial Nitric Oxide Production by Chenodeoxycholic Acids in Patients with Hepatobiliary Diseases.

“…Thus, by virtue of the enterohepatic circulation, the plasma concentrations of all individual bile acids are kept at low levels. [1][2][3][4][5] But, in patients with hepatobiliary diseases such as liver cirrhosis or bile duct obstruction, the plasma concentrations of bile acids are markedly elevated. [1][2][3][4][5] Bile acids have been reported to exert vasoactive effects, such as vasodilatory effects.…”

“…[1][2][3][4][5] But, in patients with hepatobiliary diseases such as liver cirrhosis or bile duct obstruction, the plasma concentrations of bile acids are markedly elevated. [1][2][3][4][5] Bile acids have been reported to exert vasoactive effects, such as vasodilatory effects. 6,7) Obstructive jaundice or isolated cholaemia produced by choleductocaval anastomosis induces arterial hypotension due to peripheral vasodilation, and peripheral pressor responses to contractile agonists are blunted.…”