Disease relevance of saccharolactone

• This experiment was designed to test the hypothesis that orally administered D-glucaro-1,4-lactone might be excreted in the bile and thus suppress the activity of biliary beta-glucuronidase, which is believed to play a key role in the development of pigment gallstones [1].
• D-Glucaro-1,4-lactone, 50 to 2,600 mu moles, was fed to adult Sprague-Dawley rats which had a bile fistula and were kept in metabolic cages for bile and urine collection [1].

High impact information on saccharolactone

• Glucuronic acid is released from the lipid-linked glucuronide by a beta-glucuronidase in liver that is active at neutral pH and is not inhibited by saccharolactone [2].
• Rats receiving saccharolactone excreted significantly less bilirubin in their bile, suggesting that inhibition of beta-glucuronidase decreased intestinal absorption of bilirubin [3].
• One rat of each pair received an intraduodenal infusion of rat bile plus breast-milk; the other rat received a similar amount of bile and milk plus the beta-glucuronidase inhibitor saccharolactone [3].
• Adding saccharolactone, a beta-glucuronidase inhibitor, or N-acetylglucosaminolactone and N-acetylgalactosaminolactone, beta-N-acetylglucosaminidase inhibitors, to capacitated spermatozoa under the same conditions as the hyaluronidase inhibitors did not decrease fertilization [4].
• OBJECTIVE: The protective effects of D-glucaro 1,4-lactone (1,4-GL) against oxidative/nitrative protein damage (determined by parameters such as levels of protein carbonyl groups and nitrotyrosine residues) to human plasma treated with peroxynitrite (ONOO(-)) or hydroperoxide (H(2)O(2)) were studied in vitro [5].

Biological context of saccharolactone

• The metabolic disposition kinetics of diflunisal, a compound undergoing transformation to an acyl and phenyl glucuronide, were studied in rats under control conditions and following administration of D-glucaro-1,4-lactone, a potent and specific beta-glucuronidase inhibitor [6].
• Conjugated dothiepin and northiaden were hydrolyzed with beta-glucuronidase, and their hydrolysis inhibited with 1,4 saccharolactone [7].
• The study indicates that these two substrates bind at different catalytic sites of the enzyme and, on molar base, conjugated bilirubin had higher affinity for the enzyme and less degree of inhibition by D-glucaro-1,4-lactone than PGA [8].

Anatomical context of saccharolactone

• D-glucaro-1,4-lactone treatment resulted in a significant decrease in beta-glucuronidase activity in plasma, urine, and hepatic microsomes [6].
• Glucarate is normally present in tissues and body fluids and is in equilibrium with D-glucaro-1,4-lactone, a natural inhibitor of beta-glucuronidase activity [9].

Associations of saccharolactone with other chemical compounds

• Preparations of human hepatic microsomes (final concentration : 1 mg prot./ml), were incubated for 1 hr in 0.1 M Tris buffer, pH 7.4, containing 10 mM MgCl2, in the presence of UDP-glucuronic acid (4 mM), saccharolactone (4 mM), and a detergent [10].

Analytical, diagnostic and therapeutic context of saccharolactone

• Oral administration of D-glucaro-1,4-lactone decreased biliary beta-glucuronidase concentration, slowed bile flow rate and hence decreased biliary beta-glucuronidase secretion.(ABSTRACT TRUNCATED AT 250 WORDS)[1]
• The modified assay combined improvements described separately in previous reports, including pH adjustment by standard addition of buffers rather than by titration, an optimum pH of 2.3 for converting D-glucaric acid to 1,4-glucarolactone, and the use of the relation reciprocal of absorbance versus concentration for calculating unknowns [11].

References