Abstract:
:The first required step in ecdysteroid (molting hormone) biosynthesis, dietary cholesterol (C) conversion to 7-dehydrocholesterol (7dC) via 7,8-dehydrogenation, is mediated by a microsomal cytochrome-P450 monooxygenase specific to the larval prothoracic gland. A subsequent series of unknown "black-box" oxidations of 7dC result in the unusual ring geometry (cis-A/B) and functionality (6-keto-7-ene-14-alpha-ol) of the ecdysteroids and has been thought to involve the initial formation of alpha-5,6-epoxy-7-dehydrocholesterol (alpha epo7dC). Pharmacological studies indicated that conversion of C to 7dC in prothoracic gland homogenates was strongly and equally inhibited by the isomeric cholesterol substrate analogues alpha- and beta-5,6-epoxycholesterol (alpha- and beta epoC) and alpha- and beta-5,6-iminocholesterol (alpha- and beta iminoC). With respect to the conversion of C to ecdysteroids by disrupted glands, however, the two alpha-isomeric substrates were 10-fold more inhibitory than were their beta-analogues. Indeed, alpha amino C was as active as the non-specific pyrimidyl cytochrome-P450 monooxygenase inhibitor fenarimol that shows moderate toxicity in many insect species. All four cholesterol analogues competitively inhibited cholesterol 7,8-dehydrogenation, but only alpha epoC and possibly alpha iminoC were desaturated to delta 7-products. Although the KmS (and KiS) for all the substrates were similar (1.7-6.0 x 10(-5) M), the Vmax for alpha epoC dehydrogenation was eight-fold higher than that of C, making it a superior substrate for following this reaction in ecdysteroidogenic tissues rich in endogenous C. The 7,8-dehydrogenation of alpha epoC and alpha iminoC by prothoracic glands would produce the potentially reactive intermediates, alpha epo7dC and alpha imino7dC, respectively. They, in turn, could then undergo facile, acid-catalyzed ring-opening to the allylic-stabilized carbo-cation electrophiles. These very reactive, transient species, if formed in the active site of the monooxygenase, would then alkylate either the heme group or the apoprotein of the cytochrome or both, leading to the irreversible inhibition of the enzyme. The present data show that alpha epoC and probably alpha iminoC are mechanism-based suicide inhibitors of the enzyme catalyzing cholesterol 7,8-dehydrogenation and may be the prototypes of a new class of selective insect control agents.
journal_name
Insect Biochem Mol Bioljournal_title
Insect biochemistry and molecular biologyauthors
Warren JT,Rybczynski R,Gilbert LIdoi
10.1016/0965-1748(95)00007-isubject
Has Abstractpub_date
1995-06-01 00:00:00pages
679-95issue
6eissn
0965-1748issn
1879-0240pii
0965-1748(95)00007-Ijournal_volume
25pub_type
杂志文章abstract::Fourteen different cDNA fragments encoding serine proteinases were isolated by reverse transcription-PCR from cotton boll weevil (Anthonomus grandis) larvae. A large diversity between the sequences was observed, with a mean pairwise identity of 22% in the amino acid sequence. The cDNAs encompassed 11 trypsin-like sequ...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章
doi:10.1016/j.ibmb.2004.06.001
更新日期:2004-09-01 00:00:00
abstract::PFA (Phalera flavescens agglutinin) lectin purified from larvae of the lobster moth (P. flavescens) shows a strong binding ability specific to the N-acetyllactosamine (Galβ1-4GlcNAc) site. We determined the genomic and cDNA sequences of the PFA gene, which consists of five exons and spans approximately 5 kb of a genom...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章
doi:10.1016/j.ibmb.2014.09.005
更新日期:2014-11-01 00:00:00
abstract::Using in vitro methods, we investigated the transfer of cholesterol from larval Manduca sexta midgut to the hemolymph lipoprotein, lipophorin, and the transfer of cholesterol from lipophorin to larval fat body. In the midgut, transfer of free cholesterol shows saturation kinetics, but the apparent Km is higher than th...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章
doi:10.1016/s0965-1748(02)00051-6
更新日期:2002-09-01 00:00:00
abstract::A blood meal induces the ovaries of female Aedes aegypti mosquitoes to produce ecdysteroid hormones that regulate many processes required for egg maturation. Various proteins involved in the intracellular transport and biosynthesis of ecdysteroid precursors have been identified by analysis of Drosophila melanogaster m...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章
doi:10.1016/j.ibmb.2005.01.011
更新日期:2005-05-01 00:00:00
abstract::A pheromonotropic peptide was isolated from brain-suboesophageal ganglion complexes of the adult female gypsy moth, Lymantria dispar, using a 5-step HPLC purification protocol and an in vivo bioassay in Helicoverpa zea. The intact peptide was sequenced by automated Edman degradation. The L. dispar pheromone biosynthes...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章
doi:10.1016/0965-1748(94)90111-2
更新日期:1994-09-01 00:00:00
abstract::We have previously cloned and characterized BmJHE, a juvenile hormone (JH)-selective esterase (JHE) that is important for JH titer regulation in the silkworm Bombyx mori. Here, we sought to determine whether multiple genes might function as JH-specific esterase in this species. We searched for putative carboxyl/cholin...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章
doi:10.1016/j.ibmb.2009.12.015
更新日期:2010-02-01 00:00:00
abstract::Inflammation is an important vertebrate defense mechanism against ecto-parasites for which ticks have evolved numerous mechanisms of modulation. AM-33 and TSGP4, related lipocalins from the soft ticks Argas monolakensis and Ornithodoros savignyi bind cysteinyl leukotrienes with high affinity as measured by isothermal ...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章
doi:10.1016/j.ibmb.2008.06.002
更新日期:2008-09-01 00:00:00
abstract::It is noted that insect insulin/insulin-like growth factor/target of rapamycin signaling is critical for the regulation of metamorphosis in holometabolous insects. However, the molecular mechanism remains undetermined. Our previous findings reveal that RNA interference (RNAi)-mediated knockdown of an insulin gene (LdI...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章
doi:10.1016/j.ibmb.2018.10.001
更新日期:2018-12-01 00:00:00
abstract::NADH-dependent glutamate synthase (Nadh-Gogat; EC 1.41.14) was purified 766-fold from the fat body of 5th instar larvae of the silkworm with a final specific activity of 13.8 units/mg protein by a produce including ammonium sulfate fraction, Q-Sepharose HP ion exchange column chromatography, Blue Sepharose FF affinity...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章
doi:10.1016/s0965-1748(98)00019-8
更新日期:1998-07-01 00:00:00
abstract::The male ejaculate contains a multitude of seminal fluid proteins (SFPs), many of which are key reproductive molecules, as well as sperm. However, the identification of SFPs is notoriously difficult and a detailed understanding of this complex phenotype has only been achieved in a few model species. We employed a rece...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章
doi:10.1016/j.ibmb.2018.12.002
更新日期:2019-01-01 00:00:00
abstract::In this overview, some of the more significant recent developments in bioengineering natural products from insects with use or potential use in modern medicine are described, as well as in utilisation of insects as models for studying essential mammalian processes such as immune responses to pathogens. To date, insect...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章,评审
doi:10.1016/j.ibmb.2011.05.007
更新日期:2011-10-01 00:00:00
abstract::Specific binding to midgut membrane proteins is required for the toxicity of insecticidal crystal proteins (ICP) from Bacillus thuringiensis. A direct relationship between toxicity and binding has been proposed. It has been hypothesized that sharing of a single receptor by more than one ICP could lead to the occurrenc...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章
doi:10.1016/s0965-1748(97)00039-8
更新日期:1997-07-01 00:00:00
abstract::The three-member Egf gene family from the polydnavirus Microplitis demolitor bracovirus (MdBV) encodes novel proteins distinguished by a shared cysteine-rich motif. Prior studies determined that one family member, Egf1.0, inhibits melanization of hemolymph from the moth Manduca sexta by disabling phenoloxidase activat...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章
doi:10.1016/j.ibmb.2010.04.009
更新日期:2010-07-01 00:00:00
abstract::Three laminarinases (LAM, LIC 1, and LIC 2) and two cellulases (CEL 1 and CEL 2) were purified to homogeneity from Periplaneta americana midguts. These beta-glucanases are secreted by salivary glands, stabilized by calcium ions, and have pH optima around 6. LAM (46 kDa) is active only on laminarin, native or with oxid...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章
doi:10.1016/s0965-1748(03)00121-8
更新日期:2003-11-01 00:00:00
abstract::Caste differentiation in the female honey bee is one of the most intriguing polyphenism phenomena. This developmental switch depends on the differential expression of entire suites of the genes involved in the larval fate between the queens and workers. In this study, we compared the transcriptome differences between ...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章
doi:10.1016/j.ibmb.2012.05.004
更新日期:2012-09-01 00:00:00
abstract::UDP-glycosyltransferases (UGTs) catalyze the conjugation of a variety of small lipophilic molecules with uridine diphosphate (UDP) sugars, altering them into more water-soluble metabolites. Thereby, UGTs play an important role in the detoxification of xenobiotics and in the regulation of endobiotics. Recently, the gen...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章
doi:10.1016/j.ibmb.2014.04.003
更新日期:2014-07-01 00:00:00
abstract::Genomic DNA from tsetse flies (Diptera: Glossinidae: Glossina Wiedemann) was analyzed by hybridization using the whole M13 phage as a probe to reveal DNA fingerprinting (DNAfp) profiles. Intrapopulation variability, measured by comparison of DNAfp profiles of tsetse flies from a large colony of G. brevipalpis, showed ...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章
doi:10.1016/0965-1748(93)90111-5
更新日期:1993-12-01 00:00:00
abstract::A cDNA for a midgut chymotrypsin, induced by a blood meal, has been cloned and sequenced from the mosquito Aedes aegypti. The 938 base sequence codes for a 268 amino acid protein, which contains an 18-residue signal peptide and a seven-residue activation peptide. The deduced amino acid sequence contains several featur...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章
doi:10.1016/s0965-1748(97)00001-5
更新日期:1997-04-01 00:00:00
abstract::cAMP-dependent-protein kinase (PKA) is a central player of the adipokinetic signal that controls the mobilization of stored lipids in the fat body. Previous studies showed that adipokinetic hormone (AKH) rapidly activates PKA from the fat body of Manduca sexta (Arrese et al. (J. Lipid. Res. 40(3): 556)). As a part of ...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章
doi:10.1016/j.ibmb.2004.08.008
更新日期:2004-12-01 00:00:00
abstract::Sex-pheromone production in the night flying female moth, Helicoverpa armigera is under neuroendocrine control due to the timely release of Pheromone Biosynthesis-Activating Neuropeptide (PBAN). Males orient to the females by upwind anemotaxis which usually leads to a successful mating. During copulation insect males ...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章
doi:10.1016/j.ibmb.2011.03.004
更新日期:2011-08-01 00:00:00
abstract::The sequence of a alpha(2)-macroglobulin (alpha(2)M) from the soft tick Ornithodoros moubata (TAM) was determined by cloning and sequencing of overlapping polymerase chain reaction (PCR) and rapid amplification of cDNA ends PCR products. The TAM cDNA sequence is 4,944 bp long and contains one open reading frame coding...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章
doi:10.1016/s0965-1748(03)00083-3
更新日期:2003-08-01 00:00:00
abstract::Mate-finding communication in many moths is mediated by sex pheromones produced by females. Since the differentiation of sex pheromones is often associated with speciation, it is intriguing to elucidate how the changes in sex pheromones are tracked by the pheromone recognition system of the males. Moths of the genus O...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章
doi:10.1016/j.ibmb.2009.12.011
更新日期:2010-01-01 00:00:00
abstract::A novel serine protease, named as scolonase, was purified and characterized from the tissue of the Korean centipede, Scolopendra subspinipes mutilans. Purified scolonase showed an apparent molecular weight of 25 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and an isoelectric point of 4.8 o...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章
doi:10.1016/j.ibmb.2003.10.003
更新日期:2004-03-01 00:00:00
abstract::The major beta-1,3-glucanase from Tenebrio molitor (TLam) was purified to homogeneity (yield, 6%; enrichment, 113 fold; specific activity, 4.4 U/mg). TLam has a molecular weight of 50 kDa and a pH optimum of 6. It is an endoglucanase that hydrolyzes beta-1,3-glucans as laminarin and yeast beta-1,3-1,6-glucan, but is i...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章
doi:10.1016/j.ibmb.2009.10.003
更新日期:2009-12-01 00:00:00
abstract::Members of the pacifastin family have been characterized as serine peptidase inhibitors (PI), but their target enzyme(s) are unknown in insects. So far, the structural and biochemical characteristics of pacifastin-like PI have only been studied in locusts. Here we report the molecular identification and functional cha...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章
doi:10.1016/j.ibmb.2009.03.005
更新日期:2009-07-01 00:00:00
abstract::We characterized a Kunitz-type protease inhibitor (Gm KTPI) obtained from the hemolymph of Galleria mellonella larvae immunized with Escherichia coli. The structural analysis of the cloned cDNA showed that it consists of 56 residues derived from the precursor of 75 amino acids. The peptide was constitutively produced ...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章
doi:10.1016/j.ibmb.2010.08.007
更新日期:2010-12-01 00:00:00
abstract::Host plasma proteins and protein digestion in larval parasitoids were studied during trophic interactions of the ectoparasitoid Habrobracon hebetor Say (Hymenoptera: Braconidae), with a host, larvae of the Indianmeal moth, Plodia interpunctella Hübner (Lepidoptera: Pyralidae). We could detect no apparent differences i...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章
doi:10.1016/s0965-1748(00)00066-7
更新日期:2000-10-01 00:00:00
abstract::The ecdysone-inducible E75 gene responsible for the 75B puff of Drosophila melanogaster encodes a family of proteins which are members of the steroid receptor superfamily. These proteins are believed to be involved in the regulation of ecdysone response. In order to investigate the evolutionary conservation of E75, we...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章
doi:10.1016/0965-1748(93)90086-8
更新日期:1993-01-01 00:00:00
abstract::Diverse color patterns on the integument of lepidopteran larvae play important roles in their survival through camouflage, mimicry, sexual signaling, and aposematism. In the silkworm Bombyx mori, many color pattern variations have been preserved in inbred strains making them a good model for elucidating the molecular ...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章
doi:10.1016/j.ibmb.2015.10.016
更新日期:2016-01-01 00:00:00
abstract::In many insect species, sperm transferred in a single mating are stored by the female in specialized organs and are gradually used to fertilize eggs. Thus, insects must have mechanisms to ensure that substantial numbers of sperm reach and become stored in the storage organs. We report here that a glycoprotein, Acp36DE...
journal_title:Insect biochemistry and molecular biology
pub_type: 杂志文章
doi:10.1016/s0965-1748(96)00064-1
更新日期:1996-09-01 00:00:00