Certain photooxidized derivatives of tryptophan bind with very high affinity to the Ah receptor and are likely to be endogenous signal substances

Journal Article · Sun Nov 15 04:00:00 EST 1987 · J. Biol. Chem.; (United States)

OSTI ID:5720714

Rannug, A; Rannug, U; Rosenkranz, H S; Winqvist, L; Westerholm, R; Agurell, E; Grafstroem, A K

The purpose of the present study was to determine whether ultraviolet light (UV) irradiation of amino acids produces compounds with affinity for the Ah receptor. Aqueous solutions of L-tryptophan were exposed to radiation from an unfiltered high-pressure mercury lamp. The photoproducts formed were solvent-extracted or concentrated on Sep-Pak C18 cartridges. The concentrated extracts or eluants were treated for their ability to compete with /sup 3/H-labeled 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Binding was assayed in liver cytosolic preparations from Sprague-Dawley rats using a technique based on hydroxylapatite separation. Photoproducts with receptor affinity were formed in a time-dependent manner. Histidine and tryptamine also gave products upon UV irradiation that competed with TCDD. Commercial tryptophan, at least aged, contained trace amounts of impurities with receptor affinity. Analysis by TLC and high-pressure liquid chromatography of the photo-products of tryptophan showed a minimum of three different binding compounds. Two of the products were studied in greater detail. One of them, showing UV absorbance and yellow fluorescence, gave a molecular ion (M+) of 284 and the other gave M+ 312 but showed little UV absorption and fluorescence. The concentration, based on mass spectrometry quantifications, of the two compounds that displaced more than 50% of TCDD was found to be extremely low, giving Kd values of 0.44 nM (M+ 312) and 0.07 nM (M+ 284). The existence of high affinity receptors for oxidized amino acids is postulated and their possible role in the proliferative cellular responses to TCDD and tryptophan is discussed briefly.

• Research Organization: National Board of Occupational Safety and Health, Solna, Sweden
• OSTI ID: 5720714
• Journal Information: J. Biol. Chem.; (United States), Journal Name: J. Biol. Chem.; (United States) Vol. 262:32; ISSN JBCHA
• Country of Publication: United States
• Language: English

Related Subjects

550201 -- Biochemistry-- Tracer Techniques
560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
560300 -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AFFINITY
AMINO ACIDS
ANIMALS
AROMATICS
AZAARENES
AZOLES
BIOCHEMICAL REACTION KINETICS
BODY
CARBOXYLIC ACIDS
CHEMICAL RADIATION EFFECTS
CHEMICAL REACTIONS
CHEMISTRY
CHROMATOGRAPHY
DIGESTIVE SYSTEM
DIOXIN
ELECTROMAGNETIC RADIATION
FLUORESCENCE
GLANDS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
INDOLES
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
LIVER
LUMINESCENCE
MAMMALS
MASS SPECTROSCOPY
MEMBRANE PROTEINS
METABOLISM
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PHOTOCHEMISTRY
PROTEINS
PYRROLES
RADIATION CHEMISTRY
RADIATION EFFECTS
RADIATIONS
RATS
REACTION KINETICS
RECEPTORS
REDOX REACTIONS
RODENTS
SEPARATION PROCESSES
SPECTROSCOPY
THIN-LAYER CHROMATOGRAPHY
TIME DEPENDENCE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TRYPTOPHAN
ULTRAVIOLET RADIATION
VERTEBRATES