Biliverdin reductase isozymes in metabolism

Trends Endocrinol Metab. 2015 Apr;26(4):212-20. doi: 10.1016/j.tem.2015.02.001. Epub 2015 Feb 25.


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.

Keywords: BVRA; BVRB; bilirubin; biliverdin reductase; diabetes; heme oxygenase; obesity.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adipokines / blood
  • Adipokines / metabolism
  • Adipose Tissue / immunology
  • Adipose Tissue / metabolism
  • Animals
  • Bilirubin / blood
  • Binding Sites
  • Energy Metabolism*
  • Humans
  • Hypertriglyceridemia / blood
  • Hypertriglyceridemia / enzymology*
  • Hypertriglyceridemia / immunology
  • Hypertriglyceridemia / metabolism
  • Insulin Resistance
  • Isoenzymes / chemistry
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Models, Biological*
  • Obesity, Abdominal / blood
  • Obesity, Abdominal / enzymology*
  • Obesity, Abdominal / immunology
  • Obesity, Abdominal / metabolism
  • Oxidoreductases Acting on CH-CH Group Donors / chemistry
  • Oxidoreductases Acting on CH-CH Group Donors / genetics
  • Oxidoreductases Acting on CH-CH Group Donors / metabolism*
  • Protein Conformation
  • Signal Transduction*


  • Adipokines
  • Isoenzymes
  • Oxidoreductases Acting on CH-CH Group Donors
  • biliverdin reductase
  • Bilirubin