Biliary D-Glucaric Acid: Its Quantitation and Preventive Role in Gallstone Formation

Abstract

A method for quantitation of D-glucaric acid in bile has been developed involving extraction with tetrahexylammonium chloride, boiling for 40-60 min, and determination of the percentage inhibition of β-glucuronidase activity at 56°C and pH 4. D-glucaric acid, bilirubin, bile acid, and protein were determined in 106 human gallbladder biles obtained at autopsy, including 20 with gallstones. The mean D-glucaric acid content was 1125 ± 159 μM (mean ± SE). Biliary β-glucuronidase activity was not affected by D-glucaric acid because of 1) no difference in biliary D-glucaric acid content, either absolute or corrected for per unit of bilirubin, bile acid, or protein, between those with and those without gallstones; 2) no negative correlation between D-glucaric acid content and β-glucuronidase activity in the bile; and 3) minimal conversion of D -glucaric acid to D -glucaro-l,4-lactone at the usual pH of bile. We conclude that biliary D-glucaric acid plays no role in the prevention of gallstone formation.

Key Words:

• Biliary β-glucuronidase
• cholelithiasis
• D -glucaric acid
• D -glucaro-1,4-lactone