Isopentenyl adenine as a mediator of mevalonate-regulated DNA replication.
The model in Figure 6 may serve to explain these findings. Our previous studies have shown that mevalonic acid is essential for DNA replication and that this function is independent of its role as a cholesterol precursor. The present study suggests that the isoprene purine, isopentenyl adenine, or a related isoprene, may mediate this essential role of mevalonic acid in DNA replication. The fact that isopentenyl adenine will also reverse the inhibition of DNA synthesis caused by nalidixic acid (a compound that does not influence cholesterol synthesis and acts directly on DNA replication) suggests that isopentenyl adenine and nalidixic acid may act at a common reaction site in the process of DNA replication. Finally, these findings provide a possible mechanism by which the early steps of cholesterol synthesis may influence the rate of cell replication in normal cells. Coupled with our earlier observation that the feedback inhibition of mevalonate is lost in all malignant tumors, the present results also suggest that a derangement in these early steps of mevalonic acid metabolism may figure in the transformation of normal cells into cancer cells.
D000241:Adenosine / Q000031:analogs & derivatives*; D000818:Animals; D002453:Cell Cycle; D002784:Cholesterol / Q000096:biosynthesis / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects*; D066298:In Vitro Techniques; D007541:Isopentenyladenosine / Q000494:pharmacology*; D008798:Mevalonic Acid / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000494:pharmacology
D007541:Isopentenyladenosine; D002784:Cholesterol; D000241:Adenosine; D008798:Mevalonic Acid