ABSTRACT
3 beta, 14 alpha-Dihydroxy-5 alpha-7-en-6-one (5 alpha-ketodiol) (1) is metabolized by the prothoracic glands to 2,22-dideoxy-5 alpha-ecdysone (4) and 2-deoxy-5 alpha-ecdysone (3) but not to ecdysone (5) or any other 5 beta-metabolites. Similarly, 3 beta,5 alpha,14 alpha-trihydroxy-cholest-7-en-6-one (5 alpha-ketotriol) (8) is hydroxylated at C-22 and C-25 (9,10) of the side chain. However, 3 beta,14 alhpa-dihydroxy-cholesta-4,7-diene-6-one (ketodienediol) (11) is not metabolized. The absence of 2 beta-hydroxymetabolites for substrates (1) and (8) implies that hydroxylation at C-2 can occur only when the A-B rings are cis fused (5 beta-configuration). By contrast, the enzyme complexes that introduce hydroxyls at C-22 and C-25 do not exhibit a preference for cis over trans fusion and appraently cannot recognize the planar A-B ring configuration.
Subject(s)
Ecdysone/biosynthesis , Endocrine Glands/metabolism , Lepidoptera/metabolism , Moths/metabolism , Animals , Chromatography, High Pressure Liquid , In Vitro Techniques , LarvaABSTRACT
alpha-Ecdysone (2beta,3beta,14alpha,22R,25-pentahydroxy-5beta-cholest-7-en-6-one) has been identified as the metabolism product of 3beta,14alpha-dihydroxy-5beta-cholest-7-en-6-one in isolated prothoracic glands of the tobacco hornworm, Manduca sexta. In contrast, 3beta-hydroxy-5beta-cholest-7-en-6-one is metabolized to 14-deoxy-alpha-ecdysone and a variety of intermediates all lacking the 14-hydroxy group. The results suggest that either the normal precursor for the synthesis of alpha-ecdysone by prothoracic glands is a sterol more highly oxygenated than cholesterol or that hydroxylation of a minimally oxygenated precursor at C-14 must precede introduction of the C-6 ketone and/or delta7 bond. The data further suggest that several alternative hydroxylation routes may exist for the latter steps of alpha-ecdysone biosynthesis.
Subject(s)
Cholestenes/metabolism , Cholestenones/metabolism , Lepidoptera/metabolism , Moths/metabolism , Sterols/metabolism , Animals , Chromatography , Ecdysone/metabolism , Hydroxysteroids/metabolism , Ketosteroids/metabolism , Sebaceous Glands/metabolism , Silicon Dioxide , Structure-Activity RelationshipABSTRACT
Makisterone A is the predominant ecdysone in the 96 +/- 4-hour-old embryo of the large milkweed bug and it is the first molting hormone with a C-24 alkyl substituent of the side chain to be isolated and identified from an insect. In addition, unknown compounds that may represent other C28 ecdysones were detected in very low concentrations. The milkweed bug could well possess a biosynthetic-metabolic pathway for C28 molting hormones instead of or in addition to known pathways for the C27 ecdysones.