Precursor/product studies of macrophage synthesis of nitrite, nitrate and N-nitrosamines

Conference · Fri May 01 04:00:00 EDT 1987 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6374876

Iyengar, R; Marletta, M A

Previous experiments showed that nitrite, nitrate and N-nitrosamine synthesis was carried out by both stimulated macrophages (M phi) and a number of M phi cell lines. Here the authors report the precursor to NO/sub 2//sup -/, NO/sub 3//sup -/, and the source of the nitrosating agent. Previous kinetic studies established a time lag for NO/sub 2//sup -//NO/sub 3//sup -/ synthesis during which protein synthesis required for product formation occurred. Medium change after the protein synthesis phase showed that L-arginine was the only amino acid essential for the synthesis. Other precursors were homoarginine, arginine methyl ester, arginine infinity-hydroxamate, argininamide and the peptide arginine-aspartate. Glutamine, citrulline, ornithine, hydroxylamine and D-arginine were among some of the non-precursors. Canavanine though not a precursor inhibited arginine-derived NO/sub 2/-/NO/sub 3//sup -/ synthesis while D-arginine had no effect. When /sup 15/N-arginine (guanido-/sup 15/N/sub 2/, 95%) was used, GC/MS results showed that all the NO/sub 2//sup -//NO/sub 3//sup -/ synthesized was derived exclusively from these two guanido nitrogens. Similar labeling experiments carried out in the presence of morpholine showed that the isotopic enrichment of N-nitrosomorpholine was the same as that of NO/sub 2//sup -//NO/sub 3//sup -/ synthesized, suggesting that the nitrosating agent is a common intermediate. In conclusion, NO/sub 2//sup -//NO/sub 3//sup -/ and N-nitrosomorpholine synthesis by stimulated macrophages is derived specifically from the two guanido nitrogens of arginine.

• Research Organization: Massachusetts Institute of Technology, Cambridge
• OSTI ID: 6374876
• Report Number(s): CONF-870644-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 46:6
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
AMINO ACIDS
ANIMAL CELLS
ARGININE
BIOSYNTHESIS
CARBOXYLIC ACIDS
CONNECTIVE TISSUE CELLS
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MACROPHAGES
NITRATES
NITRITES
NITROGEN 15
NITROGEN COMPOUNDS
NITROGEN ISOTOPES
NITROSAMINES
NITROSO COMPOUNDS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXYGEN COMPOUNDS
PHAGOCYTES
PRECURSOR
SOMATIC CELLS
STABLE ISOTOPES
SYNTHESIS
TRACER TECHNIQUES