Lee, DH Kim, DH 2024-01-21T15:07:53Z 2024-01-21T15:07:53Z 2021-09-04 1999-09 0049-8254 https://pubs.kist.re.kr/handle/201004/141973 1. 2-(Allylthio)pyrazine (2-AP) has been demonstrated to protect the liver against toxicants by inhibiting CYP2E1 activity. Since 2-mercaptopyrazine (2-MP) is presumed to be a metabolite of 2-AP, the experiments were performed to determine whether rat liver microsomal and/or cytosolic preparations could catalyse the S-methylation of 2-MP. 2. It was found that both rat liver microsomes and cytosol could catalyse the S-methylation of 2-MP. The microsomal activity displayed biphasic substrate kinetics, with apparent K-m = 8.44+/-2.68 and 417+/-74 mu M for the high- and low-affinity activities respectively. The high-affinity activity had an apparent K-m for S-adenosyl-L-methionine (Ado-Met) of 3.52 mu M. The cytosolic activity also displayed biphasic substrate kinetics, with apparent K-m of 3.26+/-0.62 and 91.6+/-23.1 mu M for the high- and low-affinity activities respectively. 3. The microsomal S-methylation of 2-MP was inhibited by 2,3-dichloro-alpha-methylbenzylamine (DCMB), SKF-525A and benzylamine, known microsomal thiol methyltransferase (TMT) inhibitors, whereas cytosolic activity was inhibited by anisic acid and 3-chlorobenzoate, which also inhibit cytosolic thiopurine methyltransferase (TPMT). Both activities were inhibited by S-adenosyr-L-homocysteine (Met-Hcy). 4. These results suggest that both TMT and TPMT may be involved in the in vivo methylation of 2-MP. English TAYLOR & FRANCIS LTD THIOL METHYLTRANSFERASE THIOPURINE METHYLTRANSFERASE BIOCHEMICAL-PROPERTIES 2-(ALLYLTHIO)PYRAZINE INHIBITION ASSAY ACID S-methylation of 2-mercaptopyrazine in rat liver microsomes and cytosol Article 10.1080/004982599238155 1 XENOBIOTICA, v.29, no.9, pp.909 - 916 XENOBIOTICA 29 9 909 916 scie scopus 000082984700004 2-s2.0-0032830055 Pharmacology & Pharmacy Toxicology Pharmacology & Pharmacy Toxicology Article THIOL METHYLTRANSFERASE THIOPURINE METHYLTRANSFERASE BIOCHEMICAL-PROPERTIES 2-(ALLYLTHIO)PYRAZINE INHIBITION ASSAY ACID 2-mercaptopyrazine