Inactivation of GABA transaminase by 4-acryloylphenol.
Previous study showed that 4-hydroxybenzaldehyde is a competitive inhibitor of GABA transaminase. As a result, 4-acryloylphenol was synthesized as a 4-hydroxybenzaldehyde analogue, and shown to inactivate potently the enzyme in a time-dependent manner. The inactivation was protected by alpha-ketoglutarate, indicating that it occurs at the active site of the enzyme. Beta-mercaptoethanol also prevented the enzyme from inactivation. The possible mechanism involving a Michael addition was proposed to rationalize the inactivation.
Tao
Yun-Hai
YH
Institute of Materia Medica, College of Life Science and Technology, Huazhong University of Science and Technology, 430074 Wuhan, China.
Xu
Hui-Bi
HB
Yang
Xiang-Liang
XL
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D001547:Benzaldehydes / Q000737:chemistry; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007656:Ketoglutaric Acids / Q000494:pharmacology; D008623:Mercaptoethanol / Q000494:pharmacology; D010636:Phenols / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013997:Time Factors
C513650:4-acryloylphenol; D001547:Benzaldehydes; D004791:Enzyme Inhibitors; D007656:Ketoglutaric Acids; D010636:Phenols; D008623:Mercaptoethanol; D000612:4-Aminobutyrate Transaminase; C011483:4-hydroxybenzaldehyde