Hepatic microsomal. omega. -oxidation of leukotriene B/sub 4/

Conference · Sat Mar 01 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5320592

Mukhtar, H; Bik, D P; Das, M; Bickers, D R

In this study the authors investigated the metabolism of LTB/sub 4/ by rat hepatic microsomes. /sup 3/H-LTB/sub 4/ (9 ..mu..M) was incubated for 20 min in the presence3 of oxygen, NADPH and liver microsomes (1.5 mg). Incubation was followed by extraction and analysis by HPLC. Metabolite identification was based on cochromatography with reference standards. At least three radioactive peaks were observed; two of which were ..omega..-oxidation products 20-OH-LTB/sub 4/ and 20-COOH-LTB/sub 4/. The rate of formation of 20-OH-LTB/sub 4/ (14.6 nmoles/min/mg protein) was higher than that of 20-COOH-LTB/sub 4/ (2.5 nmoles/min/mg protein). The third radioactive peak remains unidentified. Product formation was negligible with boiled microsomes. LTB/sub 4/ ..omega..-hydroxylase activity required NADPH and oxygen, was linear with respect to incubation time and protein, and was maximal at pH 7.4. Enzyme activity was inhibited (>90%) by carbon monoxide, SKF 525A (1 mM), but was not affected by ..cap alpha..-naphthoflavone. Phenobarbital (PB, 80 mg/kg for 3 days), AROCLOR 1254 (100 mg/kg for 3 days) or 3-methylcholanthrene (40 mg/kg for 3 days) administration to rats resulted in only slight (<20%) or no increase in LTB/sub 4/ ..omega..-hydroxylase activity. However, the formation of the unidentified peak was increased (>100%) by PB treatment. These results suggest that ..omega..-oxidation is the major pathway for biotransformation of LTB/sub 4/ in liver microsomes and that this reaction is mediated by cytochrome P-450.

• Research Organization: Case Western Research Univ., Cleveland, OH
• OSTI ID: 5320592
• Report Number(s): CONF-8604222-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:3
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANESTHETICS
ANTICONVULSANTS
ARACHIDONIC ACID
AROMATICS
AZINES
BARBITURATES
BIOLOGICAL EFFECTS
BIOLOGICAL PATHWAYS
BODY
CARBON COMPOUNDS
CARBON MONOXIDE
CARBON OXIDES
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHALCOGENIDES
CHOLANTHRENE
CHROMATOGRAPHY
COENZYMES
CONDENSED AROMATICS
CYTOCHROMES
DIGESTIVE SYSTEM
DRUGS
ENZYME ACTIVITY
ENZYMES
GLANDS
HETEROCYCLIC COMPOUNDS
HYDROXYLASES
HYPNOTICS AND SEDATIVES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
LIVER
METABOLISM
METABOLITES
MICROSOMES
MONOCARBOXYLIC ACIDS
NADP
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANOIDS
ORGANS
OXIDES
OXIDOREDUCTASES
OXYGEN COMPOUNDS
PHENOBARBITAL
PIGMENTS
PROTEINS
PYRIMIDINES
SEPARATION PROCESSES
TRACER TECHNIQUES
TRITIUM COMPOUNDS