The effect of the experimental antitumor agent caracemide on brain choline acetyltransferase.
Caracemide was found to inhibit choline acetyltransferase (CAT) from rat brain. A concentration of 0.5 mM caracemide inhibited the enzyme by 93%, whereas a degradation product from caracemide, N-(methylcarbamoyloxy)acetamide, produced only a 50% inhibition. Two other degradation products, N-(methyl-carbamoyloxy)-N'-methylurea and N-hydroxy-N'-methylurea, lacked any inhibitory activity. With bovine brain CAT, caracemide showed noncompetitive inhibition with the substrate choline, Km 337 microM, Ki240 microM, Vmax 2.83 nmol acetylcholine formed/min/mg protein and mixed inhibition with the substrate acetyl-CoA, Km 21 microM, Ki 146 microM, Vmax 3.85 nmol acetylcholine formed/min/mg protein.
Ho
B T
BT
Department of Neuro-Oncology, U.T.M.D. Anderson Hospital, Houston 77030.
Tansey
L W
LW
Feiffer
R
R
Newman
R A
RA
Farquhar
D
D
Fields
W S
WS
Krakoff
I H
IH
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001921:Brain / Q000201:enzymology*; D002795:Choline O-Acetyltransferase / Q000037:antagonists & inhibitors*; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats
D000970:Antineoplastic Agents; D002795:Choline O-Acetyltransferase; C044466:caracemide; D006918:Hydroxyurea