Characterization of the arylalkylamine N -acetyltransferase in Onchocerca volvulus

Abstract

The characteristics and kinetic properties of an arylalkylamine N-acetyltransferase were studied in partially purified preparations of the human filarial parasite Onchocerca volvulus. The enzyme, which had a relative molecular mass (M(r)) of 37-38 kDa, catalyzed the acetylation of arylalkylamines but did not accept arylamines or polyamines as substrates. The optimal pH for enzyme activity was found to be 8.5 in TRIS-HCI. The apparent Michaelis constant (K(m)) and maximum velocity (Vmax) determined from Lineweaver-Burk plots for tryptamine were 1.8 microM and 29 nmol min-1 mg protein-1, respectively. Except for the catecholamines, the other arylalkylamines such as 5-hydroxytryptamine (5-HT), tyramine, and octopamine similarly exhibited high affinities and reaction rates. Whereas the enzyme is inhibited by metals and p-chloro-mercuribenzoate, it is inactivated neither by amethopterin nor by cystamine and is thereby distinguished from the mammalian arylamine N-acetyltransferase. Like other N-acetyltransferases whose function is the regulation of intracellular amine levels, the enzyme may have a role in the inactivation of excess biogenic amine in this parasite.

Onchocerca volvulus -neurotransmitter tyramine is a biomarker for river blindness

“…Accordingly, a high level of activity of this decarboxylase was identified in the third-stage larvae of O. volvulus, suggesting a critical role for this neurotransmitter in the worm's development (23), a point in fact that readily justifies the reduced concentration of biomarker NATOG in doxycyclinetreated patients, which leads to the sterilization of adult worms (16,17). Based on literature precedents, we concluded that N-acetylation of tyramine by arylalkylamine N-acetyltransferase (AANAT) is the second metabolic step (24,25) in the biosynthesis of NATOG. Importantly, N-acetylation and monoamine oxidation by monoamine oxidases (MAOs) are the two deactivation mechanisms of excess neurotransmitters that nematodes use before excretion.…”

“…Importantly, N-acetylation and monoamine oxidation by monoamine oxidases (MAOs) are the two deactivation mechanisms of excess neurotransmitters that nematodes use before excretion. To support this notion further, an AANAT has been isolated from O. volvulus, which has a high degree of specificity for arylalkylamines like tyramine, tryptamine, or octopamine over arylamines or polyamines (25).…”