Abstract
Many drug metabolism reactions take place in the endoplasmic reticulum of hepatocytes in mammals. The oxidative reactions may lead to either activation or inactivation of the drug, but the conjugation with glucuronic acid inactivates the biological effects of the aglycone (1). In the monooxygenase system, NADPH gives electrons to cytochrome P450, although NADH can also serve as an electron donor (2). The conjugation reaction, glucuronide formation, is catalyzed by UDPglucuronosyltransferase (E.C. 2.4.1.17). In this reaction, aglycones are conjugated with a d -glucuronic acid residue donated by UDPglucuronic acid (3). In mammalian liver there exists also a nucleotide pyrophosphatase (E.C. 3.6.1.9). This enzyme hydrolyzes several nucleotides including UDPglucuronic acid, NADP, NADPH, NAD, and NADH (4). This nucleotide pyrophosphatase competes with drug metabolism by consuming the same substrates and coenzymes. However, little is known about microsomal nucleotide pyrophosphatase compared to drug-metabolizing enzymes. In this work, the rat liver microsomal nucleotide pyrophosphatase and its effects on substrates and coenzymes needed in drug hydroxylation and conjugation have been studied in vitro.
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© 1977 Plenum Press, New York
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Puhakainen, E. (1977). Nucleotide Pyrophosphatase as a Competitor of Drug Hydroxylation and Conjugation in Rat Liver Microsomes. In: Jollow, D.J., et al. Biological Reactive Intermediates. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-4124-6_26
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DOI: https://doi.org/10.1007/978-1-4613-4124-6_26
Publisher Name: Springer, Boston, MA
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