Possible inhibition mechanism of dobutamine hydrochloride as potent inhibitor for human glucose-6-phosphate dehydrogenase enzyme

Glucose-6-phosphate dehydrogenase (G6PD) is the first rate-limiting enzyme in the pentose phosphate pathway. One of the enzyme's most important functions is the production of a reducing agent that is essential for preserving the level of reduced glutathione (GSH). However, some chemicals, such as industrial waste and the active ingredients of several drugs, can cause reduction or blockage in this enzyme's activity. This case causes the occurrence of anemia by damaging erythrocytes. In this study, the G6PD enzyme was purified 21,981 fold with affinity chromatography and the effects of the active ingredients of some antiarrhythmic drugs on enzyme activity were investigated within vitroandin silicomethods. We found that dobutamine hydrochloride significantly decreased enzyme activity and its inhibitory constant (K-i) value was calculated as 19.02 +/- 4.83 mM. Thein vitrostudy results also show that dobutamine hydrochloride is a potent inhibitor of enzyme activity. We also found that dobutamine hydrochloride inhibits the hG6PD enzyme's activity by causing structural alterations in substrate and coenzyme binding sites. Communicated by Ramaswamy H. Sarma

Automated summary

Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway, responsible for producing a reducing agent necessary for maintaining reduced glutathione levels. This study investigated the effects of certain drugs on G6PD enzyme activity using purification and in vitro/in silico methods. The results showed that dobutamine hydrochloride significantly reduced enzyme activity by causing structural alterations in substrate and coenzyme binding sites.