(In)organic anions as carbonic anhydrase inhibitors
Giuseppina De Simone1, Claudiu T Supuran
1Istituto di Biostrutture e Bioimmagini-CNR, via Mezzocannone 16, Naples, Italy.
Journal of Inorganic Biochemistry
|December 24, 2011
Summary
Carbonic anhydrases (CAs) are vital enzymes. This review details anion inhibition of CA enzymes, excluding sulfonamides, aiding understanding of their mechanisms and potential therapeutic applications.
Area of Science:
- Biochemistry
- Enzymology
- Molecular Biology
Background:
- Carbonic anhydrases (CAs) are ubiquitous metalloenzymes found across all kingdoms of life.
- Five genetic families (α, β, γ, δ, ζ-CAs) exist, with varying degrees of investigation.
- Inhibition studies are crucial for understanding CA function and developing therapeutic agents.
Purpose of the Study:
- To review existing data on the inhibition of various carbonic anhydrase families by inorganic and organic anions.
- To exclude sulfonamides and their bioisosteres from the scope, as previously reviewed.
- To discuss the role of CA inhibitors in understanding enzyme mechanisms and potential clinical applications.
Main Methods:
- Comprehensive literature review of studies investigating carbonic anhydrase inhibition.
- Focus on anion inhibitors, excluding specific classes (sulfonamides, sulfamates, sulfamides).
- Analysis of data across different CA families (α, β, γ, ζ) and organisms.
Main Results:
- Extensive data exists for the inhibition of α, β, γ, and ζ-CA families by a wide range of anions.
- The δ-class of carbonic anhydrases remains less explored regarding anion inhibition.
- Anions serve as valuable tools for probing CA catalytic and inhibition mechanisms.
Conclusions:
- Anion inhibitors are critical for elucidating carbonic anhydrase mechanisms and designing novel therapeutic strategies.
- Understanding CA inhibition is relevant for treating disorders involving these enzymes.
- Environmental CO(2) fixation by CAs and the impact of inhibitors are also considered.
Related Concept Videos
01:29Roles of Electrolytes: Chloride and Bicarbonate
Chloride ions contribute to the osmotic pressure gradient distinguishing the intracellular fluid (ICF) from the extracellular fluid (ECF). They counterbalance positively charged ions in the ECF and ensure its electrochemical stability. The renal system's process of chloride absorption and release generally mirrors that of sodium ions.
Conditions such as hypochloremia can arise from insufficient chloride reabsorption by the kidneys, often compounded by extended bouts of diarrhea, vomiting, or...
Conditions such as hypochloremia can arise from insufficient chloride reabsorption by the kidneys, often compounded by extended bouts of diarrhea, vomiting, or...
01:22Bicarbonate-Carbonic Acid Buffer
The carbonic acid-bicarbonate buffer system is critical for maintaining the body's pH balance. It operates on the equilibrium:
01:29Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
Indirect-acting cholinergic agonists are agents that interact with the acetylcholinesterase enzyme in the synaptic cleft, preventing the breakdown of acetylcholine into choline and acetate. Consequently, the concentration of acetylcholine in the synaptic cleft increases. These agonists can be classified into reversible and irreversible inhibitors based on their duration of action.
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
02:54Ions as Acids and Bases
Salts with Acidic Ions
Salts are ionic compounds composed of cations and anions, either of which may be capable of undergoing an acid or base ionization reaction with water. Aqueous salt solutions, therefore, may be acidic, basic, or neutral, depending on the relative acid-base strengths of the salt’s constituent ions. For example, dissolving the ammonium chloride in water results in its dissociation, as described by the equation:
Salts are ionic compounds composed of cations and anions, either of which may be capable of undergoing an acid or base ionization reaction with water. Aqueous salt solutions, therefore, may be acidic, basic, or neutral, depending on the relative acid-base strengths of the salt’s constituent ions. For example, dissolving the ammonium chloride in water results in its dissociation, as described by the equation:
00:49Gravimetry: Inorganic And Organic Precipitating Agents
In gravimetry, the precipitant is chosen carefully to obtain a pure solid that can be easily filtered. Common inorganic precipitants can be used to determine several cations and anions. In some cases, the formation of the same precipitate can be used to determine the cation and the anion. For example, the reaction of barium and chromate ions to give barium chromate is used to determine both barium and chromate. However, precipitates such as hydroxides, oxalates, and metal ammonium phosphates...
01:18Indirect-Acting Cholinergic Agonists: Mechanism of Action
Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex, leading to...
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex, leading to...