Juvenile hormone epoxide hydrolase (JHEH) is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

that inactivates insect

juvenile hormone Juvenile hormones (JHs) are a group of acyclic sesquiterpenoids that regulate many aspects of insect physiology. The first discovery of a JH was by Vincent Wigglesworth. JHs regulate development, reproduction, diapause, and polyphenisms.The chem ...

s. This inactivation is accomplished through hydrolysis of the

epoxide In organic chemistry, an epoxide is a cyclic ether () with a three-atom ring. This ring approximates an equilateral triangle, which makes it strained, and hence highly reactive, more so than other ethers. They are produced on a large scale ...

functional group contained within these hormones into diols. JHEH is one of two enzymes involved in the termination of signaling properties of the various juvenile hormones. The other is juvenile-hormone esterase, or JHE. The first observation of activity from JHEH was in ''

Rhodnius prolixus ''Rhodnius prolixus'' is the principal triatomine vector of the Chagas parasite due to both its sylvatic and domestic populations in northern South America as well as to its exclusively domestic populations in Central America. It has a wide ran ...

'' and ''

Schistocerca gregaria The desert locust (''Schistocerca gregaria'') is a species of locust, a periodically swarming, short-horned grasshopper in the family Acrididae. They are found primarily in the deserts and dry areas of northern and eastern Africa, Arabia, and sou ...

''. JH esterase was also first observed in this same work.

Mechanism

JH esterase and epoxide hydrolase are the only known enzymes involved in primary degradation of JH. The inactivated carboxylic acid products of juvenile hormone esterase can be reactivated in peripheral tissues by

esterification In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...

restoring its biological activity. In contrast, the juvenile hormone diols that are the product of the epoxide hydrolase are very hydrophilic and cannot be converted back to JH. Thus, this enzyme permanently terminates the action of juvenile hormone, unlike JH esterase. The enzyme mechanism involves the addition of water at the secondary carbon, C-10. In ''

Trichoplusia ni The cabbage looper (''Trichoplusia ni'') is a medium-sized moth in the family Noctuidae, a family commonly referred to as owlet moths. Its common name comes from its preferred host plants and distinctive crawling behavior. Cruciferous vegetab ...

'', JH has been found to be the preferred substrate of this enzyme as compared with JH acid.

Isoforms

Two forms of JHEH have been cloned from '' Leptinotarsa decemlineata'', which are found in all tissues studied. Knockdown of these enzymes by injected appropriate

RNA interference RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by ...

has been found to increase JH titers, prolong larval development, and delay adult emergence, all symptoms of excessive levels of JH.

Structure

JHEH is a membrane associated protein, and by photoaffinity labeling has been shown to be a 50 kDA protein in ''

Manduca sexta ''Manduca sexta'' is a moth of the family Sphingidae present through much of the Americas. The species was first described by Carl Linnaeus in his 1763 ''Centuria Insectorum''. Commonly known as the Carolina sphinx moth and the tobacco hawk mo ...

''. It has been noted by several that properties of JHEH are similar to those of animal

microsomal epoxide hydrolase In enzymology, a microsomal epoxide hydrolase (mEH) () is an enzyme that catalyzes the hydrolysis reaction between an epoxide and water to form a diol. This enzyme plays a role in the uptake of bile salts within the large intestine. It functio ...

. Sequence alignments showed that the exact

catalytic triad A catalytic triad is a set of three coordinated amino acids that can be found in the active site of some enzymes. Catalytic triads are most commonly found in hydrolase and transferase enzymes (e.g. proteases, amidases, esterases, acylases, li ...

of the animal enzyme (Asp-226, Glu-403 and His-430) is present in JHEH. In addition, the X-ray structure of ''

Bombyx mori The domestic silk moth (''Bombyx mori''), is an insect from the moth family Bombycidae. It is the closest relative of ''Bombyx mandarina'', the wild silk moth. The silkworm is the larva or caterpillar of a silk moth. It is an economically imp ...

'' JHEH was recently determined.;

Post translational modification

Juvenile hormone diol is acted on by juvenile hormone diol kinase, to give juvenile hormone diol

phosphate In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phosph ...

, with the phosphate attached to the hydroxyl group on carbon atom 10. This modification greatly enhances the water solubility, making it easier to excrete.

References

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