[The biological role of D-glucaric acid and its derivatives: potential use in medicine].
D-glucaric acid is a natural non-toxic compound produced in small amounts by mammals, including humans. In mammals, D-glucaric acid and D-glucaro-l,4-lactone are end-products of the D-glucuronic acid pathway. The enzyme D-glucuronolactone dehydrogenase has been found to be responsible for the oxidation of the lactone of D-glucuronic acid to D-glucaro-l,4;6,3-dilactone. This dilactone hydrolyzes spontaneously in aqueous solution to D-glucaro-l,4-lactone, a potent beta-glucuronidase inhibitor. D-glucaric acid is also found in many fruits and vegetables, with the highest concentrations found in grapefruits, apples, oranges, and cruciferous vegetables. b-glucuronidase is present in the circulation and probably all vertebrate tissues and is capable of hydrolyzing glucuronide conjugates. This enzyme is also produced by colonic microflora. Elevated b-glucuronidase activity is associated with an increased risk for various cancers, particularly hormone-dependent cancers such as breast and prostate cancer. D-glucaro-l,4-lactone increases detoxification of carcinogens and tumor promoters by inhibiting b-glucuronidase and preventing the hydrolysis of their glucuronides. D-glucaro-l,4-lactone was found to be formed from supplemented D-glucarate salt in the stomach and it is absorbed from the intestinal track, transported with the blood to different internal organs, and excreted in urine and, to a lesser extent, in bile. D-glucaro-l,4-lactone and its precursors exert their anticancer action in part through alterations in steroidogenesis accompanied by changes in the hormonal environment and proliferative status of the target organs. D-glucarates not only suppress cell proliferation and inflammation, but also induce apoptosis. By supplementing D-glucarates, one can favor the body's natural defense mechanism for eliminating carcinogens and tumor promoters and their effects.
Zółtaszek
Robert
R
Department of Pharmacology, University of Texas Health Science Center, San Antonio, TX, USA.
Hanausek
Margaret
M
Kiliańska
Zofia M
ZM
Walaszek
Zbigniew
Z
D000818:Animals; D017209:Apoptosis; D005937:Glucaric Acid / Q000031:analogs & derivatives* / Q000378:metabolism*; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D018384:Oxidative Stress; D012307:Risk Factors
C009194:saccharolactone; D005966:Glucuronidase; D005937:Glucaric Acid