A phospholipid derivative of cytosine arabinoside and its conversion to phosphatidylinositol by animal tissue.

Abstract

We have synthesized an analog (ara-CDP-DL-dipalmitin) of cytidine diphosphate diglyceride (CDP-diglyceride) in which the antitumor drug, cytosine arabinoside, is substituted for the cytidine moiety. Enzymes in rat and human liver convert this analog to phosphatidylinositol, thereby releasing cytosine arabinoside-5'-monophosphate, an obligatory intermediate in the activation of cytosine arabinoside. Unlike cytidine diphosphate diglyceride, however, ara-CDP-DL-diapalmitin is not an efficient substrate for phosphatidylglycerophosphate synthesis in liver or phosphatidylserine in Escherichia coli. The antitumor activity of ara-CDP-DL-dipalmitin in mice bearing L5178Y leukemia is described.

• Authors: C R Raetz, M Y Chu, S Srivastava, J G Turcotte
• Journal: Science (New York, N.Y.) (Science) Vol. 196 Issue 4287 Pg. 303-5 (Apr 15 1977) ISSN: 0036-8075 [Print] United States
• PMID: 191910 (Publication Type: Journal Article)

Chemical References

• Diglycerides
• Glycerides
• Phosphatidylglycerols
• Phosphatidylinositols
• Cytarabine
• Phosphotransferases
• CDPdiacylglycerol-Serine O-Phosphatidyltransferase

Topics

• Animals
• Biotransformation
• CDPdiacylglycerol-Serine O-Phosphatidyltransferase (metabolism)
• Cytarabine (analogs & derivatives, metabolism, therapeutic use)
• Diglycerides (metabolism)
• Glycerides (metabolism)
• Humans
• Leukemia, Experimental (drug therapy)
• Liver (metabolism)
• Mice
• Phosphatidylglycerols
• Phosphatidylinositols (biosynthesis)
• Phosphotransferases (metabolism)
• Rats