Molecular cloning and characterization of the human and mouse UDP- glucose dehydrogenase genes

Andrew P. Spicer, Lee A. Kaback, Terry J. Smith, Michael F Seldin

Research output: Contribution to journalArticle

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Abstract

The enzyme UDP-glucose dehydrogenase (Udpgdh) (EC 1.1.1.22) converts UDP-glucose to UDP-glucuronate, a critical component of the glycosaminoglycans, hyaluronan, chondroitin sulfate, and heparan sulfate. Although Udpgdh is a comparatively well characterized enzyme, no vertebrate genes encoding this enzyme have been reported to date. We report the cloning and characterization of the human and mouse UDP-glucose dehydrogenase genes. Mouse and human cDNAs predicted proteins of 493 and 494 amino acids, 24-25 residues longer at their carboxyl termini than the previously reported bovine Udpgdh sequence. The mouse Ugdh gene is composed of 10 exons, spanning 15 kilobases. Northern analyses indicated widespread expression of the gene in embryo and adult. Through interspecific backcross analyses, we localized the Ugdh gene to mouse chromosome 5 at approximately 39 centimorgans, suggesting that the human UGDH gene is localized to chromosome 4p13-15. Results from Southern analyses strongly suggest that Udpgdh is encoded by a single gene in the mouse. Transfection of mouse Ugdh expression vectors led to an increase in detectable Udpgdh activity in mammalian cells. Preliminary expression studies indicated that proinflammatory cytokines, such as interleukin 1β, can substantially increase the expression of human UGDH in cultured human fibroblasts, suggesting that glycosaminoglycan biosynthesis may be partly regulated by the availability of activated UDP-glucuronate, as determined by relative Udpgdh expression levels.

Original languageEnglish (US)
Pages (from-to)25117-25124
Number of pages8
JournalJournal of Biological Chemistry
Volume273
Issue number39
DOIs
StatePublished - Sep 25 1998

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Uridine Diphosphate Glucose Dehydrogenase
Cloning
Molecular Cloning
Genes
Glucuronic Acid
Uridine Diphosphate
Chromosomes
Glycosaminoglycans
Enzymes
Uridine Diphosphate Glucose
Chromosomes, Human, Pair 15
Chromosomes, Human, Pair 5
Gene encoding
Heparitin Sulfate
Chondroitin Sulfates
Biosynthesis
Hyaluronic Acid
Fibroblasts
Interleukin-1
Transfection

ASJC Scopus subject areas

  • Biochemistry

Cite this

Molecular cloning and characterization of the human and mouse UDP- glucose dehydrogenase genes. / Spicer, Andrew P.; Kaback, Lee A.; Smith, Terry J.; Seldin, Michael F.

In: Journal of Biological Chemistry, Vol. 273, No. 39, 25.09.1998, p. 25117-25124.

Research output: Contribution to journalArticle

Spicer, Andrew P. ; Kaback, Lee A. ; Smith, Terry J. ; Seldin, Michael F. / Molecular cloning and characterization of the human and mouse UDP- glucose dehydrogenase genes. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 39. pp. 25117-25124.
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