The enzyme juvenile hormone esterase (EC 3.1.1.59, systematic name methyl-(2E,6E,10R)-10,11-epoxy-3,7,11-trimethyltrideca-2,6-dienoate acylhydrolase, JH esterase) catalyzes the hydrolysis of juvenile hormone:
(1) juvenile hormone I + H2O = juvenile hormone I acid + methanol
(2) juvenile hormone III + H2O = juvenile hormone III acid + methanol
Nomenclature and function
This enzyme belongs to the family of hydrolases, specifically those acting on carboxylic ester bonds. The systematic name of this enzyme class is methyl-(2E,6E)-(10R,11S)-10,11-epoxy-3,7,11-trimethyltrideca-2,6-dienoate acylhydrolase. Other names in common use include JH esterase, juvenile hormone esterase, and juvenile hormone carboxyesterase.
Juvenile hormone (JH) controls insect metamorphosis. High JH titers maintain the larval state while a decrease in the JH titer initiates the pupation sequence as well as a change in tissue commitment away from synthesis of larval tissues to pupal tissues at the pupal stage. The drop in JH titer at the beginning of the last larval instar in the Lepidoptera appears to be due to a combination of increased metabolism and decreased synthesis. In the Lepidoptera, JH is initially metabolized by ester hydrolysis; esterases capable of hydrolyzing JH are detectable in the hemolymph at times during the last larval instar that appear to coincide with reported drops in the JH titre. The JHE's are also selective for the 2E methyl ester of the naturally occurring JH's. These studies suggest that the JHE's may be important in the regulation of the JH titre and therefore involved in the initiation of and the commitment to the pupal stage. JHE's appear to be produced by the fat body and this production can be stimulated by exogenous JH in Hyalophora pupae, a stage devoid of JHE activity. Stimulation of JHE activity by JH has also been noted recently in adults of Leptinotarsa decemlineata and pupae of Galleria mellonella. However, to date, no reported studies have examined this phenomenon during the last larval instar when these enzymes are thought to be of primary importance. Thus this laboratory undertook an investigation of the hemolymph JHE regulation during the last larval instar of the cabbage looper, Trichoplusia ni.
JH esterase induction
Juvenile hormone esterase is induced by factors naturally occurring in the head of insects. In addition, it is induced by treatment of insects with either natural juvenile hormone, with JH I being the most potent inducer. Synthetic agonists of JH have been shown to possess this same activity, albeit at a lower potency than JH I. In another study, it has been shown that factors present in the head of the insect are potent inducers of JH activity. Starvation of lepidopteran larvae also induces appearance of JH esterase.
JH esterase inhibitors
A number of compounds have been discovered which are potent inhibitors of JH esterase. Many of these are insecticides falling into two major structural groups, the phosphoamidothiolates and S-phenylphosphates; carbamate insecticides were also tested. By far the most potent inhibitor was an ethoxythiophenylphospamidothiolate, with IC50 < 1 nM. Of particular interest in this study is that ethyl and isopropyl analogs of natural JHs were NOT cleaved by the esterase, showing that it is methyl ester specific. JH I and JH III were tested at nominal concentrations of 5 μM. Later a trifluoromethyl ketone (3-octylthio-1,1,1-trifluoro-2-propanone) was shown to be a highly potent, high affinity slow, tight binding inhibitor of the JH esterase of Trichoplusia ni, the same Lepidopteran which was used in the other study in this section. This study reported very sophisticated kinetic analyses of the inhibition of this compound (acronym OTFP), JH I was shown to be degraded more readily by the enzyme than JH III, with a Km value about twice the value of JH III.