Reaction of Nitroxyl, an Aldehyde Dehydrogenase Inhibitor, with N-Acetyl-L-Cysteine

• Published in: Alcohol Vol. 20; no. 1; pp. 55 - 59
• Main Authors: Shoeman, Don W., Shirota, Frances N., DeMaster, Eugene G., Nagasawa, Herbert T.
• Format: Book Review Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 2000; Elsevier Science
• Subjects: Acetylcysteine - chemistry; Alcohol deterrent; Alcoholism and acute alcohol poisoning; Aldehyde dehydrogenase; Aldehyde Dehydrogenase - antagonists & inhibitors; Aldehyde Dehydrogenase - chemistry; Biological and medical sciences; Cyanamide; Hydroxamic Acids - chemistry; Medical sciences; N-Acetyl-L-cysteine; Nitrogen Oxides - chemical synthesis; Nitroxyl; Piloty's acid; Sulfhydryl inhibition; Sulfonamides - chemistry; Toxicology; Nitroxyl; Piloty's acid; Alcohol deterrent; Sulfhydryl inhibition; Cyanamide; N-Acetyl-L-cysteine; Aldehyde dehydrogenase; Cysteine; Antialcohol drug; Enzyme; Sulfinamide; Enzyme inhibitor; ); Structure function relationship; Trapping; Chemical reactor; Aldehyde dehydrogenase (NAD; Oxidoreductases; Mechanism of action; Chemical synthesis; Structural analysis
• ISSN: 0741-8329; 1873-6823
• DOI: 10.1016/S0741-8329(99)00056-7

Nitroxyl (HNO) is the aldehyde dehydrogenase (AlDH) inhibitor produced by catalase action on cyanamide. Incubation of N-acetyl-L-cysteine (NAC), a reagent with a free sulfhydryl group, with Piloty's acid (a nitroxyl generator) suggested that NAC was acting as a competitive “trap” for nitroxyl. Elucidation of the structure of this reaction product should give an insight as to how nitroxyl interacts with AlDH, a sulfhydryl enzyme. We now present evidence that the product formed is N-acetyl-L-cysteinesulfinamide (NACS). We have synthesized NACS and showed that this synthetic product was identical to the product formed in the trapping experiment. Both had identical RT values by reverse phase HPLC and identical RF values by TLC using three different solvent systems. The structural identification of this nitroxyl trapped product as a sulfinamide now allows the chemical confirmation of the active-site cysteine residue of AlDH as Cys-302. Published by Elsevier Science Inc.