Jejunal brush-border folate hydrolase. A novel enzyme.
Dietary folate, a vitamin required for DNA synthesis and cell regeneration, occurs as pteroylpolyglutamates that are hydrolyzed to pteroylglutamate during the process of intestinal absorption. Studies from our laboratory over the past 15 years have shown that jejunal brush-border folate hydrolase is essential and rate-limiting in folate absorption. Brush-border folate hydrolase activity and pteroylpolyglutamate hydrolysis are inhibited in disease and conditions associated with folate deficiency, including celiac and tropical sprue, the use of sulfasalazine to treat inflammatory bowel disease, and chronic alcoholism. Brush-border folate hydrolase is an exopeptidase located on the jejunal brush-border surface that liberates hydrolytic products of pteroylpolyglutamates in a progressive fashion, with a final release of pteroylglutamate. Subsequent steps in folate absorption include uptake by a brush-border folate-binding-protein receptor and transport across the brush-border membrane into the enterocyte. These steps are probably followed by an intracellular synthesis of pteroylglutamates for folate-dependent reactions and intracellular hydrolysis to pteroylglutamate for transport across the basolateral membrane to the portal circulation. In pigs, the active form of jejunal brush-border folate hydrolase has a molecular weight of 240 kd and is probably a homodimer of the 120-kd protein found after immunoprecipitation with specific antibody. Regulating the synthesis and expression of brush-border folate hydrolase may be critical to the availability of dietary folate.
Halsted
C H
CH
Department of Internal Medicine, University of California, Davis, School of Medicine 95616.
D000437:Alcoholism / Q000201:enzymology; D000818:Animals; D006801:Humans; D007583:Jejunum / Q000201:enzymology* / Q000378:metabolism / Q000648:ultrastructure; D008871:Microvilli / Q000201:enzymology; D013552:Swine; D011623:gamma-Glutamyl Hydrolase / Q000378:metabolism*
D011623:gamma-Glutamyl Hydrolase