title: Folate-Dependent Hydrolysis of Acetyl-Coenzyme A by Recombinant Human and Rodent Arylamine N-Acetyltransferases.
abstract: ArylamineN-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.
authors: Department of Pharmacology and Toxicology, James Graham Brown Cancer Center, School of Medicine, University of Louisville.
authors: Marcus W
authors: MW
authors: Stepp
authors: Department of Pharmacology and Toxicology, James Graham Brown Cancer Center, School of Medicine, University of Louisville.
authors: Galina
authors: G
authors: Mamaliga
authors: Department of Pharmacology and Toxicology, James Graham Brown Cancer Center, School of Medicine, University of Louisville.
authors: Mark A
authors: MA
authors: Doll
authors: Department of Pharmacology and Toxicology, James Graham Brown Cancer Center, School of Medicine, University of Louisville.
authors: J Christopher
authors: JC
authors: States
authors: Department of Pharmacology and Toxicology, James Graham Brown Cancer Center, School of Medicine, University of Louisville.
authors: David W
authors: DW
authors: Hein
keywords: Acetyl-Coenzyme A (AcCoA); Arylamine N-acetyltransferase (NAT); Folate; Para-aminobenzoic acid (PABA); Recombinant expression