Arylamine N-acetyltransferases (NATs) are drug and xenobiotic metabolizing enzymes that catalyze the N-acetylation of arylamines and hydrazines and the O-acetylation of N-hydroxy-arylamines. Recently, studies report that human NAT1 and mouse Nat2 hydrolyze acetyl-coenzyme A (AcCoA) into acetate and coenzyme A in a folate-dependent fashion, a previously unknown function. In this study, our goal was to confirm these findings and determine the apparent Michaelis-Menten kinetic constants (Vmax and Km) of the folate-dependent AcCoA hydrolysis for human NAT1/NAT2, and the rodent analogs rat Nat1/Nat2, mouse Nat1/Nat2, and hamster Nat1/Nat2. We also compared apparent Vmax values for AcCoA hydrolysis and N-acetylation of the substrate para-aminobenzoic acid (PABA). Human NAT1 and its rodent analogs rat Nat2, mouse Nat2 and hamster Nat2 catalyzed AcCoA hydrolysis in a folate-dependent manner. Rates of AcCoA hydrolysis were between 0.25 – 1% of the rates for N-acetylation of PABA catalyzed by human NAT1 and its rodent orthologs. In contrast to human NAT1, human NAT2 and its rodent analogs rat Nat1, mouse Nat1, and hamster Nat1 did not hydrolyze AcCoA in a folate-dependent manner. These results are consistent with the possibility that human NAT1 and its rodent analogs regulate endogenous AcCoA levels.
The first synthesis of the tetracyclic aromatic compound furo[2,3-g]thieno[2,3-e]indole ("FTI") is described. The synthetic strategy features a photochemical benzannulation based on the reaction of an α-diazo ketone and ynamide which assembles a benzothiophene equipped with substituents that enable subsequent cyclizations to generate the nitrogen and oxygen heterocyclic rings.
Clinicians should be aware of the potential for cardiovascular involvement in COVID-19 infection.
Coronavirus disease-2019 (COVID-19) is a viral illness caused by severe acute respiratory syndrome-coronavirus-2. While it primarily causes a respiratory illness, a number of important cardiovascular implications have been reported. We describe a patient presenting with COVID-19 whose hospital course was complicated by ST elevation myocardial infarction requiring percutaneous coronary intervention. The goal is to help clinicians gain awareness of the possibility of cardiovascular disease in COVID-19 infection, and maintain a high index of suspicion particularly for patients with risk factors or a prior history of cardiovascular disease.
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