Biliverdin reductase B

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RefSeq (mRNA)



RefSeq (protein)



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Biliverdin reductase B is a protein that in humans is encoded by the BLVRB gene.[1]


The BLVRB gene was localized to chromosome 19, the specific region being 19q13.13 to q13.2; this was done using fluorescence in situ hybridization.[2]

BLVRB encodes a protein that is a 206-residue monomeric enzyme.[3] The structure of BVR-B has a single-domain architecture consisting of a central parallel beta-sheet with alpha-helices on either side. This characteristic dinucleotide binding fold comprises, in this case, a seven-stranded parallel beta-sheet further extended by an antiparallel strand. In addition to the seven long strands of the main pleated sheet, a short parallel beta-sheet (strands 6a and 6c) is formed within the loop joining strand 6 and alpha-helix F. The central beta-sheet and the two groups of helices are held together mainly through hydrophobic interactions. One group of helices is made up of alpha-helices C, D, and E. The second group is composed of alpha-helices A and F and includes a short 310-helix between strands beta2 and beta3, in contrast to typical dinucleotide binding proteins in which a regular alpha-helix flanks these beta-strands. The most flexible loop in the structure corresponds to loop 120, between strand 5 and alpha-helix E, which contains residues with the highest main chain B-factors, with the exception of the N-terminal region.[4]


The final step in heme metabolism in mammals is catalyzed by the cytosolic biliverdin reductase enzymes A and B (EC[1] From a functional standpoint, it has been hypothesized that BLRVB is identical to flavin reductase (FR), an enzyme that catalyzes the NADPH-dependent reduction of FMN and Methylene Blue and, in the presence of redox couplers, the reduction of methaemoglobin.[5][6]

There have been two isoforms of BLVRB, I and II, that have been isolated and characterized. The purified enzymes were monomers with a molecular weight of about 21,000, and they used NADPH and NADH as electron donors for the reduction of biliverdin. The identified Km values of isozymes I and II for NADPH are 35.9 and 13.1 μM, respectively, whereas those for NADH are 5.6 and 8.2, indicating that NADPH rather than NADH acts as the physiological electron donor in reaction. The NADPH-dependent enzyme activities are inhibited by substrate concentrations in excess of 3-4 μM. The optimum pH of the reaction with NADPH for isozymes I and II is 8.2.[7] Flavin reductase/biliverdin-IXbeta reductase has also been shown to exhibit ferric reductase activity, with an apparent K(m) of 2.5 μM for the ferric iron. The ferric reductase reaction requires NAD(P)H and FMN. This activity is intriguing, as haem cleavage in the foetus produces non-alpha isomers of biliverdin and ferric iron, both of which are substrates for flavin reductase/biliverdin-IXbeta reductase.[8]

Clinical significance

As BLVRB is a promiscuous enzyme catalysing the pyridine-nucleotide-dependent reduction of a variety of flavins, biliverdins, PQQ (pyrroloquinoline quinone), and ferric ion. Mechanistically it is a good model for BVR-A (biliverdin-IXalpha reductase), a potential pharmacological target for neonatal jaundice, and also a potential target for adjunct therapy to maintain protective levels of biliverdin-IXalpha during organ transplantation.[9]


BLVRB binds to human heme oxygenase-1 (hHO-1) in conjunction with cytochrome p450 reductase to catalyzes the NADPH-cytochrome P450 reductase-dependent oxidation of heme to biliverdin, CO, and free iron.[10]


  1. 1.0 1.1 "Entrez Gene: Biliverdin reductase B".
  2. Saito F, Yamaguchi T, Komuro A, Tobe T, Ikeuchi T, Tomita M, Nakajima H (1995). "Mapping of the newly identified biliverdin-IX beta reductase gene (BLVRB) to human chromosome 19q13.13-->q13.2 by fluorescence in situ hybridization". Cytogenetics and Cell Genetics. 71 (2): 179–81. doi:10.1159/000134102. PMID 7656592.
  3. Yamaguchi T, Komuro A, Nakano Y, Tomita M, Nakajima H (Dec 1993). "Complete amino acid sequence of biliverdin-IX beta reductase from human liver". Biochemical and Biophysical Research Communications. 197 (3): 1518–23. doi:10.1006/bbrc.1993.2649. PMID 8280170.
  4. Pereira PJ, Macedo-Ribeiro S, Párraga A, Pérez-Luque R, Cunningham O, Darcy K, Mantle TJ, Coll M (Mar 2001). "Structure of human biliverdin IXbeta reductase, an early fetal bilirubin IXbeta producing enzyme". Nature Structural Biology. 8 (3): 215–20. doi:10.1038/84948. PMID 11224564.
  5. Shalloe F, Elliott G, Ennis O, Mantle TJ (Jun 1996). "Evidence that biliverdin-IX beta reductase and flavin reductase are identical". The Biochemical Journal. 316 (2): 385–7. doi:10.1042/bj3160385. PMC 1217361. PMID 8687377.
  6. Komuro A, Tobe T, Hashimoto K, Nakano Y, Yamaguchi T, Nakajima H, Tomita M (Jun 1996). "Molecular cloning and expression of human liver biliverdin-IX beta reductase". Biological & Pharmaceutical Bulletin. 19 (6): 796–804. doi:10.1248/bpb.19.796. PMID 8799475.
  7. Yamaguchi T, Komoda Y, Nakajima H (Sep 1994). "Biliverdin-IX alpha reductase and biliverdin-IX beta reductase from human liver. Purification and characterization". The Journal of Biological Chemistry. 269 (39): 24343–8. PMID 7929092.
  8. Cunningham O, Gore MG, Mantle TJ (Jan 2000). "Initial-rate kinetics of the flavin reductase reaction catalysed by human biliverdin-IXbeta reductase (BVR-B)". The Biochemical Journal. 345 (2): 393–9. doi:10.1042/bj3450393. PMC 1220769. PMID 10620517.
  9. Smith LJ, Browne S, Mulholland AJ, Mantle TJ (May 2008). "Computational and experimental studies on the catalytic mechanism of biliverdin-IXbeta reductase". The Biochemical Journal. 411 (3): 475–84. doi:10.1042/BJ20071495. PMID 18241201.
  10. Wang J, de Montellano PR (May 2003). "The binding sites on human heme oxygenase-1 for cytochrome p450 reductase and biliverdin reductase". The Journal of Biological Chemistry. 278 (22): 20069–76. doi:10.1074/jbc.M300989200. PMID 12626517.

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This article incorporates text from the United States National Library of Medicine, which is in the public domain.