Concerning the Role of Lanosterol and Cycloartenol in Steroid Biosynthesis

An homogenate of rat liver which was capable of converting 2-3H-lanosta-8, 24-dien-3β-ol to 2-3H-cholest-5-en-3β-ol failed to convert 2-3H-9,19-cyclolanost-24-en-3β-ol to 2-3H-cholest-5-en-3β-ol. However, both substrates underwent reduction at C-24,25. 2-3H-9,19-Cyclolanost-24-en-3β-ol was not converted to 2-3H-lanosta-8,24-dien-3β-ol. Both the presence and biosynthesis (from 2-14C-mevalonate) of 9,19-cyclolanost-24-en-3β-ol were demonstrated in vivo in corn seedlings. The latter were also shown to contain 24ξ-stigmast-5-en-3β-o1 as their dominant sterol with lesser amounts of 24ξ-ergost-5-en-3β-ol and 24ξ-stigmasta-5, trans22-dien-3β-ol. A very small amount of cholest-5-en-3β-ol and traces of 9,19-cyclolanostan-3β-ol and 24-methylene-9,19-cyclolanostan-3β-ol were detected. The three major sterols as well as stigmasta-5,24(28)-dien-3β-ol and 24-methylene-9,19-cyclolanostan-3β-ol (but not lanosta-8,24-dien-3β-ol) were shown to be labeled after incubation with 2-14C-mevalonate in vivo. The corn seedlings, when presented with either lanosta-8,24-dien-3β-ol (labeled biosynthetically with 14C or chemically with tritium) or labeled 9,19-cyclolanost-24-en-3β-ol (similarly biosynthetically or chemically labeled), produced labeled 4-desmethyl-Δ5-sterols, primarily 24ξ-stigmast-5-en-3β-ol and stigmasta-5, 24(28)-dien-3β-ol. The yields were nearly the same from either substrate. The latter data, which were obtained in vivo with an angiosperm, confirm earlier observations made in vivo with an alga and with tissue cultures of an angiosperm. They indicate that lanosta-8,24-dien-3β-ol (lanosterol) and its 9,19-cyclo derivative (cycloartenol) are both acceptable precursors in the biosynthesis of the major sterols of photosynthetic organisms. However, the data obtained with the liver homogenate demonstrate that a typical (nonphotosynthetic) tissue of the animal kingdom is more restricted in its enzymatic capability. The liver preparation did not contain an isomerase for the opening of the 9,19-cyclo grouping, and, except for the Δ24-reductase, the enzymes in the pathway would not accept the 9,19-cyclosteroid. Consequently, discrimination between lanosta-8,24-dien-3β-ol and its 9,19-cyclo derivative in liver is made at two points in the sterol pathway (cyclization and utilization), whereas in photosynthetic systems only one point (cyclization) governs the choice.