Species differences in the conjugation of 4-hydroxy-3-methoxyphenylethanol with glucuronic acid and sulphuric acid

Abstract

The biosynthesis of the glucuronide and sulfate conjugates of 4-hydroxy-3-methoxyphenylethanol was demonstrated in vitro by using the high-speed supernatant and microsomal fractions of liver respectively. These 2 conjugates were also produced simultaneously by using the post-mitochondrial fraction of rat, rabbit or guinea-pig liver. Only the glucuronide was synthesized by human liver and only the sulfate by mouse and cat livers. Neither of these conjugates was formed by the kidney or the small or large intestine of the rat. A high sulfate-conjugating activity was observed in mouse kidney; the rate of sulfation of 4-hydroxy-3-methoxyphenylethanol with kidney homogenate and high-speed supernatant preparations was 1.8 times greater than with liver preparations. The sulfo-conjugates of 4-hydroxy-3-methoxyphenylethanol and 4-hydroxy-3-methoxyphenylglycol were also formed by enzyme preparations of rabbit adrenal and rat brain; the glycol was the better substrate in the latter system. Mouse brain did not possess any sulfotransferase activity. For the conjugation of 4-hydroxy-3-methoxyphenylethanol by rabbit liver, the Km for UDP-glucuronic acid was 0.22 mM and that for Na2SO4 was 3.45 mM. The sulfotransferase has a greater affinity for 4-hydroxy-3-methoxyphenylethanol than has glucuronyltransferase, as indicated by their respective Km values of 0.036 and 1.3 mM. Sulfate conjugation of 4-hydroxy-3-methoxyphenylethanol predominates in most species of animals.