Capsaicin: a potent inhibitor of carbonic anhydrase isoenzymes.

Betul Arabaci,Ilhami Gulcin,Saleh Alwasel

doi:10.3390/molecules190710103

Betul Arabaci, Ilhami Gulcin + Show 1 more

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https://doi.org/10.3390/molecules190710103

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Abstract

Carbonic anhydrase (CA, EC 4.2.1.1) is a zinc containing metalloenzyme that catalyzes the rapid and reversible conversion of carbon dioxide (CO2) and water (H2O) into a proton (H+) and bicarbonate (HCO3–) ion. On the other hand, capsaicin is the main component in hot chili peppers and is used extensively used in spices, food additives and drugs; it is responsible for their spicy flavor and pungent taste. There are sixteen known CA isoforms in humans. Human CA isoenzymes I, and II (hCA I and hCA II) are ubiquitous cytosolic isoforms. In this study, the inhibition properties of capsaicin against the slow cytosolic isoform hCA I, and the ubiquitous and dominant rapid cytosolic isozymes hCA II were studied. Both CA isozymes were inhibited by capsaicin in the micromolar range. This naturally bioactive compound has a Ki of 696.15 µM against hCA I, and of 208.37 µM against hCA II.

Highlights

Carbonic anhydrase (CA) enzymes are virtually ubiquitous in all living systems and have important roles in pH regulation, carboxylation reactions, fluid balance, bone resorption, tumorigenicity, calcification, the synthesis of bicarbonate and in many other pathological and physiological processes [1,2,3,4]
The vanillylamine moiety of capsaicin is biologically synthesized from phenylalanine
The logic of working with capsaicin was first to identify a potent CA inhibitor because phenolic compounds with aromatic rings have been previously identified as inhibitors of CA

Summary

Introduction

Carbonic anhydrase (CA) enzymes are virtually ubiquitous in all living systems and have important roles in pH regulation, carboxylation reactions, fluid balance, bone resorption, tumorigenicity, calcification, the synthesis of bicarbonate and in many other pathological and physiological processes [1,2,3,4]. As seen in Scheme 1, to regenerate the basic form of the enzyme, a proton is transferred from the active site to the solvent. Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) comes from the plants of genus Capsicum and is a pungent constituent of capsicum fruits, which are used extensively in condiments in Asian, African, and Latin American countries [19]. It is used in a number of over-the-counter weight loss products because of its potential role in increasing metabolic activity [20]. We identify the potential inhibition profile and mechanism for human CA isoenzymes I, and II (hCA I, and II), which are widely used in the food and pharmaceutical industries

Results and Discussion

Experimental

Conclusions