Cimetidine is a histamine H2-receptor antagonist which is used in gastrointestinal
diseases. Although this drug is designed for H2 receptor, it can also attach to other enzymes.
Alkaline phosphatase (ALP) is an important enzyme used for obtaining inorganic phosphate
from organic phosphorylated substrate in microorganisms.
In this study, effect of cimetidine on the ALP of Escherichia coli and Saccharomyces cerevisiae
was investigated and compared. Cultured cells were disrupted by ultrasound and the cell
free extract was used for enzyme assay. The results showed that cimetidine inhibited ALP
with un-competitive and competitive inhibition in E. coli and S. cerevisiae, respectively. Lower IC50 and Ki of
the drug in E. coli determined that the drug bound to ALP of E. coli with higher affinity than the ALP of S.
cerevisiae. The proposed molecular modeling suggested that, in E. coli, cimetidine bound to Mg2+ ion of active
site, while in S. cerevisiae, the drug bound to Zn2+ ion. In conclusion, different patterns of pH, temperature profile,
kinetic parameter, and type of inhibition demonstrated that the ALP of E. coli and S. cerevisiae were
isozymes and cimetidine bound to these isozymes with different mechanisms.