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

Publisher Website
Google Scholar
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.

This publication has 30 references indexed in Scilit: