David A. Schooley

Chemical structure and absolute configuration of a juvenile hormone from grasshopper corpora allata in vitro

Abstract One juvenile hormone was isolated from culture medium containing isolated corpora allata of the grasshopper Schistocerca vaga (Orthoptera: Acrididae) and was shown by microchemical methods to be methyl (2 E , 6 E ) - (10 R ) - 10, 11-epoxy-3, 7, 11-trimethyldodeca-2, 6-dienoate. This compound (JH III), which occurs in a sphingid moth Manduca sexta , is the first juvenile hormone identified in an insect order other than the Lepidoptera. Grasshopper organs incorporate both [2− 14 C] acetate and [methyl- 14 C] methionine into JH III showing de novo biosynthesis, but no indication of the synthesis of JH I or JH II was seen.

Environmental degradation of the insect growth regulator methoprene: V. Metabolism by houseflies and mosquitoes☆

Abstract The metabolism of methoprene ( I , isopropyl ( 2E,4E )-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate, trademark Altosid) was investigated in larval mosquitoes and houseflies. The most abundant primary metabolite in third- and fourth-instar Aedes and fourth-instar Culex larvae was the hydroxy ester while the hydroxy acid predominated in third-instar Musca larvae. Biological isomerization of the double bond at C-2 in I (i.e., conversion of ( E ) to ( Z )) was an effective mode of insect detoxication, but these dipterans apparently cannot isomerize the (2 Z ) isomer of I to methoprene. In general, piperonyl butoxide and tri ortho cresyl phosphate slightly increased the morphogenetic activity of I in these insects.

Precocene II metabolism: Comparative in vivo studies among several species of insects, and structure elucidation of two major metabolites

Abstract Several species of insects, exhibiting varying responsiveness to the juvenile hormone antagonist precocene II (6,7-dimethoxy-2,2-dimethylchromene), were challenged topically with a tritiated preparation of the title compound. Metabolism of [ 3 H]precocene II was subsequently examined by withdrawing hemolymph samples from treated animals at appropriate time intervals and characterizing the extractable radiolabel chromatographically. Quantitative (or qualitative) differences observed between the respective metabolic profiles were found not correlative with specimen sensitivity to precocene. Production of two heretofore unreported metabolites, identified by spectral and chemical means as O -β-glucosides of 6- and 7-monodemethylated precocene II, was demonstrated in both sensitive and insensitive species. No evidence for the presence of a hemolymphborne, biologically effective “activated metabolite” produced in vivo by precocene-susceptible insects could be found. The latter finding may well argue for in situ bioactivation of precocene at the target tissue(s) by these sensitive insects.

Hydration of an 18O epoxide by a cytosolic epoxide hydrolase from mouse liver

Abstract The mechanism of enzymatic epoxide hydration by a cytosolic or 100,000 g soluble mammalian liver enzyme (in contrast to the microsomal enzymes) was examined by monitoring 18 O distribution following chemical and enzymatic hydrations of 16 O or 18 O epoxide labeled (±) 1-(4′-ethylphenoxy)-3, 7-dimethyl-6, 7-epoxyoctane. Acid catalyzed hydration of the 18 O epoxide in 16 O water, and hydration of the 16 O epoxide in 18 O water, indicated that attack by water was predominantly on the tertiary carbon (C-7). Enzymatic epoxide hydration led to attack predominantly on secondary carbon (C-6). These data are consistent with water attacking as a nucleophile in the enzymatic reaction.

Cholesterol and bile acids via acetate from the insect juvenile hormone analog methoprene

Abstract Metabolism of the insect growth regulator methorpene by a steer produced labeled cholesterol, cholic acid, and deoxycholic acid. Cholesterol and deoxycholic acid were degraded chemically by Kuhn-Roth and Barbier-Wieland oxidations to show catabolism of [5-14C] methoprene to [2-14C] acetate. Unless radioactive residues are rigorously characterized as primary metabolites rather than natural products, misinterpretations will occur when assessing metabolic pathways for extremely biodegradable compounds such as methoprene.

CONJUGATION REACTIONS OF PESTICIDE METABOLITES WITH LIPIDS IN ANIMALS

Abstract The last decade has seen the discovery of a number of conjugation reactions of pesticide metabolites with lipids. Improvements in isolation techniques have allowed the identification of conjugates which would previously have been regarded as unknowns, and it is probable that numerous lipid conjugates exist but have escaped identification. We review the known types of these conjugation reactions, together with specific examples of each class: 1) certain acidic metabolites are susceptible to chain elongation by inclusion into the normal fatty acid biosynthetic pathway and the resultant products have a net addition of from one to as many as seven acetate units; 2) conjugation of acidic metabolites with glycerides and/or cholesterol, yielding lipophilic esters, is being discovered with increasing frequency; and 3) hydroxyl-containing metabolites are known to conjugate with natural fatty acids to form lipophilic esters. In addition to the above transformations which afford conjugates more lipophilic than the metabolite, two examples are known of formation of polar lipid conjugates. One is the incorporation of acidic metabolites of cycloprate, an acaricide, into phospholipids; the other is the formation of bile acid conjugates with an acidic metabolite of the experimental insecticide fluvalinate.