CDNA CLONING, CHARACTERIZATION, AND TISSUE-SPECIFIC EXPRESSION OF HUMAN XANTHINE DEHYDROGENASE XANTHINE-OXIDASE

We isolated cDNAs encoding xanthine dehydrogenase (XD; xanthine:NAD+ o xidoreductase, EC 1.1.1.204) from a human liver cDNA library. The comp lete nucleotide sequence of human XD was determined; the deduced amino acid sequence encoded a protein of 1336 amino acid residues of M(r) 1 47,782. Human XD possessed many of the signature sequences typical of XDs from flies and rodents, including an unusual cysteine distribution , a potential 2Fe/2S binding site, and a putative molybdopterin cofact or binding domain. Analysis of potential NAD binding sites suggested a simple hypothesis for the conversion of human XD into the oxygen meta bolite forming xanthine oxidase (XO; xanthine:oxygen oxidoreductase, E C 1.1.3.22). Using a human XD complementary RNA hybridization probe, w e found a 5100-base RNA in human liver by RNA blot-hybridization analy sis. This RNA exhibited tissue-specific distribution that may be perti nent to XD- and XO-mediated oxygen radical injury in ischemia/reperfus ion and inflammation. A second 4500-base RNA was detected in some tiss ues and may arise through differential transcription termination.