Ranitidine induces inhibition and structural changes in sucrase.

Area of Science:

• Biochemistry
• Enzymology

Background:

• Ranitidine is a histamine-2 receptor antagonist used to reduce gastric acidity.
• Congenital sucrase-isomaltase deficiency (CSID) is treated with yeast sucrase.
• Investigating drug interactions with therapeutic enzymes is crucial for safety and efficacy.

Purpose of the Study:

• To investigate the effect of ranitidine on yeast sucrase activity.
• To determine the mechanism and kinetics of ranitidine inhibition on sucrase.

Main Methods:

• Enzyme activity assays were performed to measure sucrase inhibition.
• Kinetic parameters (Ki, IC50) were calculated.
• Fluorescence spectroscopy was used to detect conformational changes upon ranitidine binding.

Main Results:

• Ranitidine demonstrated noncompetitive inhibition of yeast sucrase.
• The inhibition constant (Ki) was approximately 2.3 mM, and IC50 was 2.2 mM.
• Ranitidine binding induced conformational changes in sucrase, affecting both free enzyme and enzyme-substrate complex, evidenced by fluorescence quenching and red-shift.

Conclusions:

• Ranitidine inhibits yeast sucrase activity through noncompetitive binding.
• The observed conformational changes suggest a direct interaction affecting enzyme function.
• These findings are important for understanding potential drug-enzyme interactions in CSID treatment.