title: Chloromethyl ketones are insulin-like stimulators of lipid synthesis in locust fat body.
abstract: N alpha-tosyl-L-lysine chloromethyl ketone (TLCK) stimulates lipid synthesis in locust fat body in vitro, and is able to reverse the inhibitory effects of AKH-I on lipid synthesis. Effective stimulatory concentrations of TLCK were in the range of 0.2-1.0 mM. Similar stimulatory effects were also achieved with phenylalanine chloromethyl ketone (PheCK) and leucine chloromethyl ketone (LeuCK), but not with tosyl-phenylalanine chloromethyl ketone (TPCK), dansyl-glu-gly-arg-CK, chloroacetone, chloroacetic acid, chloroacetamide, chloroacetaldehyde, chloroacetyl-L-leucine or acetylated or fluorescamine-labelled TLCK, PheCK, and LeuCK. The level of stimulation caused by TLCK was dependent on incubation time, so that after a 5-h preincubation of fat body tissue with TLCK the stimulated rate was severalfold higher than the control. TLCK also increased the rate of uptake of trehalose and uridine, but not glucose, deoxyglucose or glycine. Increasing concentrations of bovine serum albumin (BSA) in the incubation medium caused a reduction in the rate of TLCK-stimulated acetate uptake, such that levels of uptake were no higher with 1% BSA than in the controls. A range of more specific protease and kinase inhibitors was tested, but none caused stimulation; thus the mode of action of TLCK on the stimulation of acetate uptake has yet to be identified. Elucidation of the mode of action of TLCK may facilitate the development of novel compounds for insect pest control.
authors.affiliation: Department of Biology, Birkbeck College, University of London, England. michael.lee@unilever.com
authors.forename: M J
authors.initials: MJ
authors.lastname: Lee
authors.forename: G J
authors.initials: GJ
authors.lastname: Goldsworthy
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D006110:Grasshoppers / Q000378:metabolism*; D007301:Insect Hormones / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008055:Lipids / Q000096:biosynthesis*; D009479:Neuropeptides / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D014107:Tosyllysine Chloromethyl Ketone / Q000494:pharmacology
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D007301:Insect Hormones; D007328:Insulin; D008055:Lipids; D009479:Neuropeptides; D009842:Oligopeptides; C044833:adipokinetic hormone; D014107:Tosyllysine Chloromethyl Ketone; D012710:Serum Albumin, Bovine; D011761:Pyrrolidonecarboxylic Acid