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All rights reserved. http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RALRNzmL06ZCOV2HlCRKwGipUbcIPZCuqHv7jeL126iLw#_5 http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/version 1.4 http://www.tkuhn.ch/bel2nanopub/RALRNzmL06ZCOV2HlCRKwGipUbcIPZCuqHv7jeL126iLw#_4 http://www.w3.org/ns/prov#value The heme breakdown product biliverdin is rapidly reduced to bilirubin by the cytosolic enzyme biliverdin reductase. Reduction of biliverdin to bilirubin occurs in all mammals, but in some non-mammals, such as birds, amphibians, and reptiles, biliverdin is the end product of heme catabolism and is excreted in e.g., egg shells and manure (Lane, 1998). Since bilirubin is highly lipophilic, it is excreted as the glucuronide conjugate. The increased water solubility of bilirubin diglucuronide facilitates its excretion with bile as the bile pigments. Bilirubin production is two to three times elevated in newborns compared with normal adults, because of the switching from fetal to adult hemoglobin (Maines and Trakshel, 1992). Approximately 5% of newborns suffer from neonatal jaundice, or hyperbilirubinemia. If the bilirubin levels become dangerously high, bilirubin passes through the blood-brain barrier and can cause neuronal damage associated with kernicterus (Gourley, 1997). The most common treatment for hyperbilirubinemia is phototherapy, in which the jaundiced infant is exposed to blue light. The therapeutic effect is mediated by photoisomerization of unconjugated bilirubin, resulting in more polar and readily excretable photoisomers (McDonagh and Lightner, 1985). Recently, alternative treatment with competitive inhibitors of HO activity, such as stannic mesoporphyrin (single dose of 6 umol/kg), has shown to prevent and to reverse bilirubinemia (Kappas et al., 1995a, 2001). CO has been considered a dangerous poisonous gas for a long time (Johnson et al., 1999). It is usually generated during the incomplete burning of organic materials. Bernard reported already in 1857 that CO could bind to hemoglobin. In fact, this odorless, colorless, tasteless gas binds about 200 times better to hemoglobin than oxygen, resulting in the formation of carboxyhemoglobin. This subsequently results in decreased oxygen release to the metabolizing tissues and ultimately death (Johnson et al., 1999). CO was shown to be an endogenous metabolic product in man by Sjoestrand (1949), who also observed that the rate of CO production was elevated in patients with increased destruction of erythrocytes (Sjoestrand, 1949a,b). The hypothesis that heme is the source of endogenous CO production in mammals was confirmed in vivo by investigators who used radioactive tracers to show that the -meso carbon of heme is oxidized to CO and bilirubin (Coburn et al., 1967). The rate of CO production in the human body is normally approximately 16 umol/h (Marks, 1994), but it can get 10-fold higher in pathological circumstances, such as hemolysis (Coburn et al., 1966). http://www.tkuhn.ch/bel2nanopub/RALRNzmL06ZCOV2HlCRKwGipUbcIPZCuqHv7jeL126iLw#_4 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/12869663 http://www.tkuhn.ch/bel2nanopub/RALRNzmL06ZCOV2HlCRKwGipUbcIPZCuqHv7jeL126iLw#_5 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RALRNzmL06ZCOV2HlCRKwGipUbcIPZCuqHv7jeL126iLw#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/12869663 http://www.tkuhn.ch/bel2nanopub/RALRNzmL06ZCOV2HlCRKwGipUbcIPZCuqHv7jeL126iLw#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RALRNzmL06ZCOV2HlCRKwGipUbcIPZCuqHv7jeL126iLw#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RALRNzmL06ZCOV2HlCRKwGipUbcIPZCuqHv7jeL126iLw#_4 http://www.tkuhn.ch/bel2nanopub/RALRNzmL06ZCOV2HlCRKwGipUbcIPZCuqHv7jeL126iLw#pubinfo http://www.tkuhn.ch/bel2nanopub/RALRNzmL06ZCOV2HlCRKwGipUbcIPZCuqHv7jeL126iLw http://purl.org/dc/terms/created 2014-07-03T14:30:14.806+02:00 http://www.tkuhn.ch/bel2nanopub/RALRNzmL06ZCOV2HlCRKwGipUbcIPZCuqHv7jeL126iLw http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RALRNzmL06ZCOV2HlCRKwGipUbcIPZCuqHv7jeL126iLw http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234