Lanosterol, cholesterol metabolism

See also Presqualene Pyrophosphate, Lanosterol, Cholesterol Biosynthesis, Steroid Metabolism, Steroid Hormone Synthesis... 

According to earlier studies, acetate, mevalonate, and cholesterol (5) as well as cycloartenol (and lanosterol) (294) are significantly incorporated into tomatidine, solasodine, solanidine, solanocapsine, and/or spirostanols. Cholest-4-en-3-one and 26-hydroxycholesteroI were shown to be the first products of cholesterol metabolism in potato plants (295). The (25/ )- and... 

C]-(35)-2,3-epoxysqualene and its racemate have been prepared by two routes in a metabolically non-labile position relative to the demethylation of lanosterol to cholesterol (equation 70 and 71). The racemic [24,30-14C]-2,3-epoxysqualene, 192, has been obtained163 by condensation of (35, 3/ )-2,3-epoxytrisnorsqualene aldehyde 193 with freshly prepared 14C-labelled isopropylidenephosphorane, 194 (equation 70). 

From Lanosterol to Cholesterol Takes Approximately 20 Steps Summary of Cholesterol Biosynthesis Lipoprotein Metabolism... 

Concerning the metabolism of triterpenes and steroids, quite a number of P450 catalyzed transformations are very important, namely the 14a-demethyla-tion of lanosterol [50], the side-chain cleavage of cholesterol [51]and pregnenes [52], and the desaturation of ring A of androgens with concomitant oxidative removal of C(19) [53]. The latter reaction is catalyzed by human placental aromatase, associated with a NADPH-dependent reductase, and requires three moles of oxygen and three moles of NADPH in order to oxidize andro-stenedione 45 to formic acid and estrone 46, Fig. 10. 

Further work in the phylum Echinodermata shows a variable ability to biosynthesize steroids. In the class Holothuroidea and Echinoidea, the representatives examined could synthesize squalene but not triterpenoids or sterols from acetate. However, several examples from the class Asteroidea were able to synthesize squalene, lanosterol, and other steroids. In the later stages of steroid metabolism it was shown that cholesterol was converted into cholest-7-enol via cholestanol. 

Cytochrome P450 enzyme system The cytochromes P450 are mixed-function oxidases that require both NADPH and O. They are involved in a number of reactions in the conversion of lanosterol to cholesterol, as well as important steps in the synthesis of steroid hormones. Cytochromes P450 are very important in the detoxification of xenobiotics and in the metabolism of drags. 

Relatively little is known about plant sterols. (Most of the research effort in steroid metabolism has been expended in the investigation of steroid-related human diseases.) It appears, however, that the initial phase of plant sterol synthesis is very similar to that of cholesterol synthesis with the following exception. In plants and algae the cyclization of squalene-2,3-epoxide leads to the synthesis of cycloartenol (Figure 12.30) instead of lanosterol. Many subsequent reactions in plant sterol pathways involve SAM-mediated methylation reactions. There appear to be two separate isoprenoid biosynthetic pathways in plant cells the ER/cyto-plasm pathway and a separate chloroplast pathway. The roles of these pathways in plant isoprenoid metabolism are still unclear. 

A group of fungicides that inhibit squalene epoxidation has been developed primarily for use against pathogenic fungi in medicine. Epoxidation of squalene is catalyzed by squalene epoxidase (a flavoprotein) that starts the complicated cyclization of squalene. The squalene-2,3-epoxide formed by this enzyme is further metabolized to a protosterol cation intermediate, which is transformed to either cycloartenol in plants (cycloartenol synthase) or lanosterol (lanosterol synthase). Cycloartenol is the precursor to plant sterols, whereas lanosterol is the precursor of cholesterol and the other sterols in animals, and to ergosterol in plants. 

Lanosterol is converted to cholesterol by a series of oxidations, reductions, and demethylations. The required enzyme reactions have been defined and metabolic intermediates identified however, the precise sequence of reactions between lanosterol and cholesterol remains to be established [7] (Fig. 4). There is evidence for two alternative pathways that differ in the point at which the A24 double bond is reduced (Section 2.3). Both 7-dehydrocholesterol (DHC) and desmosterol have been postulated to be the... 

L and D amino acids amino acids whose stereochemistry is the same as the stereochemical standards L- and D-glyceraldehyde, respectively (3.1) lanosterol a precursor of cholesterol (21.8) leading strand in DNA replication, the strand that is continuously formed in one long stretch (10.3) Lesch-Nyhan syndrome a metabolic disease characterized by severe retardation and compulsive self-mutilation it is caused by a deficiency of an enzyme in the purine salvage pathway (23.8)... 

LSSA t Lanosterol synthase (2,3-oxidosqualene-lanosterol cyclase) Lipid metabolism/cholesterol biosynthesis... 

Preputial gland tumor sterols. III. A metabolic pathway from lanosterol to cholesterol. 

Kandutsch AA, Russell AE. Preputial gland tumor sterols. 3. A metabolic pathway from lanosterol to cholesterol. / Biol Chem. 1960 235 2256-2261. 

By incubation or perfusion of placental tissue Math acetate, this precursor is transformed into squalene, lanosterol, and cholesterol (Levitz et al., 1962, 1964 Van Leusden and Villee, 1965 C. A. Villee, 1967, 1969). On the other hand, placental perfusion with mevalonate results in the formation of squalene and lanosterol, but not of cholesterol (Tjcvitz et al., 1962). However, the in vi(7 o conversion of both acetate and mevalonate to cholesterol was found by Zelen-ski and Villee (1966) using a preparation of minced human term placenta. Tliese authors suggest that the formation of cholesterol from these precursors is through different metabolic pathways. 

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