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Reduction of blood and liver cholesterol in the rat by straight and branched chain alkyl amines
Author(s) -
Svoboda J. A.,
Wrenn T. R.,
Thompson M. J.,
Weyant J. R.,
Wood D. L.,
Bitman J.
Publication year - 1977
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02570897
Subject(s) - desmosterol , chemistry , cholesterol , sterol , reductase , campesterol , biochemistry , manduca sexta , sterol o acyltransferase , endocrinology , biology , enzyme , botany , lipoprotein , larva
The activities of a branched chain and several straight chain amines (C 12 to C 18 chain length), and the azasteroid 25‐aza‐5α‐cholestane were compared with those of 20,25‐diazacholesterol dihydrochloride, which is a potent hypocholesterolemic agent in the rat. These amines and azasteroids inhibit the Δ 24 ‐sterol reductase system in the tobacco hornworm, Manduca sexta (L.), and also block the conversion of C 28 and C 29 plant sterols to cholesterol, with a resulting accumulation of desmosterol. The effects of these compounds in the rat were determined on body weight gain, cholesterol, desmosterol, and lipid composition of blood, feces, liver, and epididymal fat pad weight. The two azasteroids and the branched chain amine, N,N‐dimethyl‐3, 7,11‐trimethyldodecanamine, had the greatest effect, reducing total plasma lipids and plasma sterols to approximately 40–50% of the levels in control rats and produced a concomitant increase in plasma and liver desmosterol. The branched chain dodecanamine caused a reduction in both feed consumption and body weight gain. The branched and straight chain dodecanamines also severely reduced epididymal fat pad weight. Our results demonstrate that the simple azasteroid, 25‐aza‐5α‐cholestane, is a more potent inhibitor of cholesterol biosynthesis than the diazasterol and that the Δ 24 ‐sterol reductase system in a mammal can be inhibited by simple, nonsteroidal, acyclic amines.