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Title: Mechanisms of vitamin K transport and metabolism in Swiss 3T3 mouse fibroblasts

Transport of vitamin K into isolated fibroblasts was followed using /sup 3/H vitamin K/sub 1/. The initial rate is saturable by 5 min. at 25..mu..M vitamin K with a Km(app) of 10..mu..M and V/sub max/ of 50 pmols/min/10/sup 6/ cells. Kinetics of uptake are biphasic with a second slower rate ensuing after 10 minutes. Insensitivity of the initial rate of uptake to FCCP or ouabain indicates an ATP-independent transport mechanism. Specificity of transport is shown by competition of uptake of /sup 3/H vitamin K by unlabelled vitamin and strong (>90%) inhibition of the initial rate by equimolar concentrations of the vitamin K analog, Chloro-K. In addition, following uptake, both vitamins K/sub 1/ and K/sub 2/ are metabolized to their respective epoxides. Vitamin K/sub 1/ epoxide is also transported into fibroblasts and metabolized to the parent quinone in a Warfarin-sensitive reaction. Following alkaline hydrolysis of isolated intracellular protein, the vitamin K-dependent amino acid, gamma carboxyglutamic acid (gla) was detected. It is concluded that vitamin K is specifically transported into fibroblasts and metabolized via the classical pathway described in liver with the concomitant production of vitamin K-dependent proteins.
Authors:
; ;
Publication Date:
OSTI Identifier:
5392358
Report Number(s):
CONF-8604222-
Journal ID: CODEN: FEPRA; TRN: 86-028417
Resource Type:
Conference
Resource Relation:
Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States); Journal Volume: 45:3; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
Research Org:
Texas A and M Univ., College Station
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; VITAMIN K; MEMBRANE TRANSPORT; METABOLISM; ATP; BIOCHEMICAL REACTION KINETICS; BIOLOGICAL PATHWAYS; FIBROBLASTS; MICE; OUABAIN; TRACER TECHNIQUES; TRITIUM COMPOUNDS; ANIMAL CELLS; ANIMALS; AROMATICS; CARBOHYDRATES; CARDIAC GLYCOSIDES; CARDIOTONICS; CARDIOVASCULAR AGENTS; COAGULANTS; CONNECTIVE TISSUE CELLS; DRUGS; GLYCOSIDES; HEMATOLOGIC AGENTS; HEPARIN ANTAGONISTS; ISOTOPE APPLICATIONS; KINETICS; LABELLED COMPOUNDS; MAMMALS; NUCLEOTIDES; ORGANIC COMPOUNDS; ORGANIC OXYGEN COMPOUNDS; QUINONES; REACTION KINETICS; RODENTS; SOMATIC CELLS; STROPHANTHINS; VERTEBRATES; VITAMINS 550501* -- Metabolism-- Tracer Techniques