Page not availableCytochrome b5 is a membrane-bound hemoprotein which acts as an electron carrier for several membrane-bound oxygenases [ PMID: There are two heme and steroid forms of b5, one found in microsomes and one found in the outer membrane of mitochondria. Two conserved histidine residues serve as axial ligands for the heme group. The structure of a number of ad consists of the juxtaposition of a zteroid domain homologous heme and steroid that trenbolone adverse effects b5 and either a flavodehydrogenase or a molybdopterin domain. By sequence By domain architecture. Add your annotation Add your annotation.
Cytochrome b5-like heme/steroid binding domain (IPR) < InterPro < EMBL-EBI
Through a multiplex promoter spanning kb, the phase II UDP-glucuronosyltransferase 1A UGT1 gene encodes at least eight differently regulated mRNAs whose protein products function as the principal means to eliminate a vast array of steroids, heme metabolites, environmental toxins, and drugs. The orphan nuclear receptors pregnane X receptor PXR and constitutive androstane receptor CAR were originally identified as sensors able to respond to numerous environmentally derived foreign compounds xenobiotics to promote detoxification by phase I cytochrome P genes.
In this report, we show that both receptors can induce specific UGT1A isoforms including those involved in estrogen, thyroxin, bilirubin, and carcinogen metabolism. Transgenic mice expressing a constitutively active form of human PXR show markedly increased UGT activity toward steroid, heme, and carcinogens, enhanced bilirubin clearance, as well as massively increased steroid clearance. The ability of PXR and constitutive androstane receptor and their ligands to transduce both the phase I and phase II adaptive hepatic response defines a unique transcriptional interface that bridges the ingestion and metabolism of environmental compounds to body physiology.
National Center for Biotechnology Information , U. Didn't get the message? Add to My Bibliography. Generate a file for use with external citation management software. Epub Mar Abstract Through a multiplex promoter spanning kb, the phase II UDP-glucuronosyltransferase 1A UGT1 gene encodes at least eight differently regulated mRNAs whose protein products function as the principal means to eliminate a vast array of steroids, heme metabolites, environmental toxins, and drugs. Comment in Nuclear receptors orchestrate detoxification pathways.
Images from this publication. See all images 5 Free text. The result is shown as the autoradiograph of a TLC plate. Results are presented as fold increase in glucuronidation activity over WTs and represent the mean and standard error. Control of steroid, heme, and carcinogen metabolism by nuclear pregnane X receptor and constitutive androstane receptor.
A Schematic representation of the UGT1 gene locus. The fold induction was calculated from the luciferase activity of VP-hPXR cotransfected cells over empty vector transfected cells. D Deletion mutants used in transfection experiments are shown diagrammatically.
The competition was performed by using a fold excess of unlabeled probe. The transfected cells were subsequently mock-treated or treated with indicated compounds for 24 h before luciferase assays. Results are shown as fold induction over solvent controls and represent the average and standard error from triplicate assays.
The P value for total bilirubin is 0. A Increased glucuronidation of three corticosteroids, corticosterone, cortisone, and cortisol by liver microsomes of VP-hPXR mice. B Blood samples from 6-week-old males were collected via retroorbital eye bleeding, and plasma were prepared and subjected to corticosterone RIA. C Twenty-four-hour urine samples were collected from 8- to week-old males and subjected to corticosterone measurement. The P value is 0. Gov't Research Support, U.