ABSTRACT
Many vertebrate species express two enzymes that are capable of catalysing the reduction of various isomers of biliverdin. Biliverdin-IXalpha reductase (BVR-A) is most active with its physiological substrate biliverdin-IXalpha, but can also reduce the three other biliverdin isomers IXbeta, IXdelta and IXgamma. Biliverdin-IXbeta reductase (BVR-B) catalyses the reduction of only the IXbeta, IXdelta and IXgamma isomers of biliverdin. Therefore, the activity of BVR-A can be measured using biliverdin-IXalpha as a specific substrate. We now show that the dimethyl esters of biliverdin-IXbeta and biliverdin-IXdelta are substrates for BVR-B, but not for BVR-A. This provides a useful method for specifically assaying the activity of both BVR-A and BVR-B in crude mixtures, using biliverdin-IXalpha for BVR-A and the dimethyl ester of either biliverdin-IXbeta or biliverdin-IXdelta for BVR-B. Human BVR-A has been suggested as a pharmacological target for neonatal jaundice. Because of the absence of a crystal structure with biliverdin bound to BVR-A, we have investigated indirect ways of examining tetrapyrrole binding. In the present study, we report that a number of sterically locked conformers of 18-ethylbiliverdin-IXalpha are substrates for human BVR-A, and discuss the implications for the biliverdin binding site. The oxidation of bilirubin-IXalpha ditaurate to biliverdin-IXalpha ditaurate is also described. We show that biliverdin-IXalpha ditaurate is a substrate for human BVR-A and discuss the possibility of using a competing substrate, which is reduced to a water soluble and excretable rubin, as a prototypic inhibitor of BVR-A.
Subject(s)
Oxidoreductases Acting on CH-CH Group Donors/metabolism , Porphyrins/metabolism , Tetrapyrroles/chemistry , Binding Sites , Humans , Kinetics , Ligands , Molecular Probe Techniques , Molecular Probes/chemical synthesis , Molecular Probes/chemistry , Oxidoreductases Acting on CH-CH Group Donors/chemistry , Protein Binding , Substrate Specificity , Tetrapyrroles/chemical synthesisABSTRACT
Stress is a costly and significant source of health problems and mental distress--with work cited as a primary stressor. This pilot study supports the effectiveness of a new workplace stress intervention: Chicken Soup for the Soul at Work Employee Groups. In this program, employee-participants met during nine weekly meetings to read inspirational workplace stories, comment, and share their own stories. A leader, chosen from and by the group, guided meetings. Utilizing a wait-list control group design, participants were randomly assigned to an experimental or wait-list group. Participants completed pretests and posttests (Coping Resources Inventory, Occupational Stress Inventory-Revised, Job Descriptive Index, Pressure Management Indicator, survey). Statistical interaction effect for subtests was evaluated using a two-way repeated measures analysis of variance. Participants exhibited improved total coping resources, cognitive/rational coping, state of mind, confidence and home/work balance. Participant comments and their continued participation in a similar company-sponsored program bolster these empirical results.
