Inducible Nitric Oxide Synthase Activity in Hepatocytes is Dependent on the Coinduction of Tetrahydrobiopterin Synthesis

  • M. Di Silvio
  • D. A. Geller
  • S. S. Gross
  • A. Nussler
  • P. Freeswick
  • R. L. Simmons
  • T. R. Billiar
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 338)

Abstract

Nitric oxide (NO) is a short-lived radical derived from the oxidation of one of the two chemically equivalent quanido nitrogens of L-arginine1. Three isoforms of the enzyme which produces NO, NO synthase (NOS), have been identified thus far. Two NOS isoforms, endothelial and neuronal are expressed constitutively (cNOS) and release relatively small amounts of NO immediately upon stimulation. A third isoform has been termed inducible NOS (iNOS) because it is not present in resting cells but is expressed if cells are exposed to inflammatory stimuli, such as bacterial lipopolysaccharide (LPS) and/or cytokines. Upon purification all three isoforms are known to be dependent on tetrahydrobiopterin (BH4) for maximal activity2–5. This observation adds to the list of four enzymes previously known to be dependent on BH4. Although the precise role of BH4 in the five-electroh oxidation of L-arginine to NO and citrulline remains uncertain, recent reports using intact cells in culture indicate that both endothelial cNOS6 and smooth muscle cell7 isoforms are dependent on BH4 availability.

Keywords

HPLC Dexamethasone Methotrexate Folate Phenylalanine 

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Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • M. Di Silvio
    • 1
    • 2
  • D. A. Geller
    • 1
    • 2
  • S. S. Gross
    • 1
    • 2
  • A. Nussler
    • 1
    • 2
  • P. Freeswick
    • 1
    • 2
  • R. L. Simmons
    • 1
    • 2
  • T. R. Billiar
    • 1
    • 2
  1. 1.Department of SurgeryUniversity of PittsburghPittsburghUSA
  2. 2.The William Harvey InstituteLondonUK

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