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Substrate specificity ofO-alkylglycerol monooxygenase (E.C. 1.14.16.5), solubilized from rat liver microsomes

  • Published:
Lipids

Abstract

Synthetic alkyl lysophospholipids (ALP) show antineoplastic activity. In the present discussion, the cytotoxicity of ALP is attributed to their accumulation in tumor cells. Some neoplastic cell species, in contrast to normal cells, cannot metabolize ALP because of a lack ofO-alkylglycerol monooxygenase (AGMO) activity. To understand the metabolic fate of ether lipids and etherlinked phospholipids, AGMO substrate specificity studies were undertaken. Thirty-five different natural and synthetic ether lipids and their metabolites (including a thioether) were tested as substrates for AGMO. The study revealed that the potent cytostatic substance, 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine is not a substrate for AGMO. Therefore, its selective toxicity to tumor cells cannot be based on the differences in direct detoxification of 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine by AGMO in normal and malignant cells. However, 1-O-octadeyl-2-O-methyl-rac-glycerol, which can be formed by phospholipase C hydrolysis, is a good substrate for AGMO.

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Abbreviations

AGMO:

O-alkylglycerol monooxygenase

ALP:

alkyl lysophospholipid

PAF:

platelet-activating factor

PC:

phosphocholine

PtH:

D,L-6-methyl-5,6,7,8-tetrahydropterine

PtH2 :

D,L-6-methyl-dihydropterine

TLC:

thin layer chromatography

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Authors and Affiliations

  1. Max-Planck-Institut für biophysikal, Chemie Am Fassberg, D-3400, Goettingen, Federal Republic of Germany

    Jochem Kötting & Hansjörg Eibl

  2. Abt. Haematologie/Onkologie, Zentrum Innere Medizin, Robert-Koch-Str. 40, D-3400, Goettingen, Federal Republic of Germany

    Clemens Unger

Authors
  1. Jochem Kötting
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  2. Clemens Unger
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  3. Hansjörg Eibl
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Kötting, J., Unger, C. & Eibl, H. Substrate specificity ofO-alkylglycerol monooxygenase (E.C. 1.14.16.5), solubilized from rat liver microsomes. Lipids 22, 831–835 (1987). https://doi.org/10.1007/BF02535539

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  • DOI: https://doi.org/10.1007/BF02535539

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