Biliverdin reductase isozymes in metabolism.
The biliverdin reductase (BVR) isozymes BVRA and BVRB are cell surface membrane receptors with pleiotropic functions. This review compares, for the first time, the structural and functional differences between the isozymes. They reduce biliverdin, a byproduct of heme catabolism, to bilirubin, display kinase activity, and BVRA, but not BVRB, can act as a transcription factor. The binding motifs present in the BVR isozymes allow a wide range of interactions with components of metabolically important signaling pathways such as the insulin receptor kinase cascades, protein kinases (PKs), and inflammatory mediators. In addition, serum bilirubin levels have been negatively associated with abdominal obesity and hypertriglyceridemia. We discuss the roles of the BVR isozymes in metabolism and their potential as therapeutic targets.
Center for Hypertension and Personalized Medicine, Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, OH 43614, USA.
Luke
L
O'Brien
Department of Exercise Science and Physical Education, Montclair State University, Montclair, NJ 07043, USA.
Peter A
PA
Hosick
Center for Hypertension and Personalized Medicine, Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, OH 43614, USA.
Kezia
K
John
Center for Excellence in Cardiovascular-Renal Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
David E
DE
Stec
Center for Hypertension and Personalized Medicine, Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, OH 43614, USA. Electronic address: Terry.Hinds@utoledo.edu.
Terry D
TD
Hinds
D054392:Adipokines / Q000097:blood / Q000378:metabolism; D000273:Adipose Tissue / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001663:Bilirubin / Q000097:blood; D001665:Binding Sites; D004734:Energy Metabolism; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D007333:Insulin Resistance; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D056128:Obesity, Abdominal / Q000097:blood / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D015398:Signal Transduction
D054392:Adipokines; D007527:Isoenzymes; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019789:biliverdin reductase; D001663:Bilirubin
BVRA; BVRB; bilirubin; biliverdin reductase; diabetes; heme oxygenase; obesity