Abstract
Carbonic anhydrase is a ubiquitous metalloenzyme that catalyzes the reversible interconversion of CO2/HCO3−. Equilibrium of these species is maintained by the action of carbonic anhydrase. Recent advances in magnetic resonance spectroscopy have allowed, for the first time, in vivo characterization of carbonic anhydrase in the human brain. In this article, we review the theories and techniques of in vivo 13C magnetization (saturation) transfer magnetic resonance spectroscopy as they are applied to measuring the rate of exchange between CO2 and HCO3− catalyzed by carbonic anhydrase. Inhibitors of carbonic anhydrase have a wide range of therapeutic applications. Role of carbonic anhydrases and their inhibitors in many diseases are also reviewed to illustrate future applications of in vivo carbonic anhydrase assessment by magnetic resonance spectroscopy.
Highlights
Carbonic anhydrase (CA, known as carbonate dehydratase or carbonic dehydratase) is a family of enzymes that are present in many different isoforms or carbonic anhydrase-related proteins.CO2 is a toxic by-product of cellular respiration, so it needs to be removed from the body
In this article we review in vivo magnetic resonance spectroscopy (MRS) theories and techniques for detecting carbonic anhydrase activities
Effect of CA inhibitors (CAIs) and CA activators on carbon dioxide–bicarbonate saturation transfer can be monitored using in vivo MRS because they alter the rate of carbon dioxide–bicarbonate interconversion
Summary
Carbonic anhydrase (CA, known as carbonate dehydratase or carbonic dehydratase) is a family of enzymes that are present in many different isoforms or carbonic anhydrase-related proteins. Assessing carbonic anhydrase activities required biopsied tissues and in vitro techniques, making it impossible to study brain CA function and dysfunction in vivo. Our laboratory discovered the phenomenon of in vivo enzyme-specific 13C magnetization transfer [38,39,40,41,42,43] and developed in vivo 13C magnetization transfer MRS techniques for measuring carbonic anhydrase-catalyzed interconversion between carbon dioxide and bicarbonate [40]. As abnormalities in CA are widespread and many drugs target or act on CA, noninvasive in vivo MRS techniques are poised to play an important role in characterizing and elucidating the function and dysfunction of carbonic anhydrase in many brain disorders as well as in monitoring treatment. Effect of CAIs and CA activators on carbon dioxide–bicarbonate saturation transfer can be monitored using in vivo MRS because they alter the rate of carbon dioxide–bicarbonate interconversion
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