title: NADH-ferric reductase activity associated with dihydropteridine reductase.
abstract: In mammals dietary ferric iron is reduced to ferrous iron for more efficient absorption by the intestine. Analysis of a pig duodenal membrane fraction revealed two NADH-dependent ferric reductase activities, one associated with a b-type cytochrome and the other not. Purification and characterization of the non-cytochrome ferric reductase identified a 31 kDa protein. MALDI-MS analysis and amino acid sequencing identified the ferric reductase as being related to the 26 kDa liver NADH-dependent quinoid dihydropteridine reductase (DHPR). The NADH-dependent DHPR ferric reductase activity was found to be pteridine-independent since exhaustive dialysis did not reduce activity and heat-inactivation destroyed activity. In intestinal Caco-2 cells, DHPR mRNA levels were found to be regulated by iron. Thus, DHPR appears to be a dual function enzyme, a NADH-dependent dihydopteridine reductase and an iron-regulated, NADH-dependent, pteridine-independent ferric reductase.
authors.affiliation: Department of Molecular and Experimental Medicine, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. plee@scripps.edu
authors.forename: P L
authors.initials: PL
authors.lastname: Lee
authors.forename: C
authors.initials: C
authors.lastname: Halloran
authors.forename: A R
authors.initials: AR
authors.lastname: Cross
authors.forename: E
authors.initials: E
authors.lastname: Beutler
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D003573:Cytochrome b Group / Q000737:chemistry; D004093:Dihydropteridine Reductase / Q000378:metabolism*; D004386:Duodenum / Q000201:enzymology; D004591:Electrophoresis, Polyacrylamide Gel; D038181:FMN Reductase; D005297:Ferrozine / Q000737:chemistry; D006801:Humans; D007501:Iron / Q000378:metabolism; D007700:Kinetics; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013053:Spectrophotometry; D013552:Swine
chemical_list: D003573:Cytochrome b Group; D012333:RNA, Messenger; D005297:Ferrozine; D007501:Iron; D004093:Dihydropteridine Reductase; D038181:FMN Reductase; D009247:NADH, NADPH Oxidoreductases; C023903:ferric citrate iron reductase