Studies on the structural background on the cross-inhibition of the products in the arginine metabolism of macrophages

A. Hrabák, T. Bajor, A. Temesi, G. Meszaros

Research output: Contribution to journalArticle

Abstract

Arginase and nitric oxide synthase (NOS) were inhibited by nitrite and putrescine, respectively. Results showed a cross- inhibition by the products of the two arginine utilizing pathways in macrophages. The kinetics of these inhibitions have been described earlier. Arginase was measured by the release of urea; NOS activity was determined by measuring 14(C)-L-citrulline synthesis from 14(C)- labeled L-arginine. The structural changes of arginase were studied by fluorescence and gel filtration experiments. Nitrite caused a decrease of tryptophane fluorescence over 5 mM concentration without dissociating the arginase oligomers as indicated by gel filtration experiments. The differences in the structural features of L-arginine substrate and putrescine inhibitor made the binding of putrescine to the active site of NOS unlikely. In conclusion, our studies suggest that nitrite causes a non-competitive inhibition of arginase based on a conformational change without the dissociation of the arginase oligomers. For putrescine inhibition we suggest an allosteric mechanism also based on a conformational change.

Original languageEnglish
Pages (from-to)299-304
Number of pages6
JournalMedical Science Monitor
Volume3
Issue number3
Publication statusPublished - 1997

Fingerprint

Arginase
Arginine
Putrescine
Macrophages
Nitrites
Nitric Oxide Synthase
Gel Chromatography
Fluorescence
Citrulline
Urea
Catalytic Domain

Keywords

  • Arginase
  • Conformational change
  • Fluorescence
  • Gel filtration
  • Macrophage
  • NO synthase

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Studies on the structural background on the cross-inhibition of the products in the arginine metabolism of macrophages. / Hrabák, A.; Bajor, T.; Temesi, A.; Meszaros, G.

In: Medical Science Monitor, Vol. 3, No. 3, 1997, p. 299-304.

Research output: Contribution to journalArticle

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