Differences in the metabolism and metabolic effects of the carbocyclic adenosine analogs, neplanocin A and aristeromycin.
Neplanocin A and aristeromycin are carbocyclic adenosine analogs that differ only in that neplanocin A contains a double bond in the carbocyclic ring, whereas this ring in aristeromycin is saturated. We have compared the metabolism and some of the metabolic effects of neplanocin A and synthetic (+/-)-aristeromycin (C-Ado) in murine leukemia L1210 cells in culture. C-Ado, as shown earlier, was not only converted to its own phosphates but also was metabolized to phosphates of carbocyclic guanosine. Both rapidly proliferating and slowly proliferating or resting cells phosphorylated C-Ado, but C-Ado was not converted to phosphates of carbocyclic guanosine in detectable amounts in cells whose growth had reached a plateau. When the metabolism of neplanocin and C-Ado was examined in the same experiment, both analogs were converted to the triphosphate analogs of ATP; no conversion of neplanocin A to the corresponding carbocyclic analogs of guanine nucleotides was detected, whereas C-Ado was converted to the carbocyclic analog of GTP in amounts that approximated the GTP pool. This difference in metabolism was associated with a marked difference in effects of the two analogs on the utilization of hypoxanthine and guanine which was inhibited by C-Ado but not by neplanocin. The failure of neplanocin A to be converted to analogs of guanine nucleotides apparently is the result of poor capacity of its monophosphate to serve as a substrate for AMP deaminase; the Vmax for deamination of neplanocin-5'-monophosphate by this enzyme was only 5% of that for C-Ado monophosphate. In contrast, neplanocin A was a better substrate than C-Ado for adenosine deaminase.
Bennett
L L
LL
Allan
P W
PW
Rose
L M
LM
Comber
R N
RN
Secrist
J A
JA
D000659:AMP Deaminase / Q000378:metabolism; D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000243:Adenosine Deaminase / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002455:Cell Division; D002460:Cell Line; D006147:Guanine / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D007536:Isomerism; D007700:Kinetics; D007939:Leukemia L1210 / Q000378:metabolism; D051379:Mice
D007042:Hypoxanthines; C030034:aristeromycin; D019271:Hypoxanthine; D006147:Guanine; C031096:neplanocin A; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D000243:Adenosine Deaminase; D000659:AMP Deaminase; D000241:Adenosine