The obligatory involvement of a C21 intermediate in the biosynthesis of cardenolides from cholesterol

Cardenolide Biosynthesis in Foxglove1

“…In similar experiments with 3'-14C-mevalonic acid the label appeared in C-18, C-19 and C-21 (6). Evidence against a route via a C20-steroid and in favour of a route via C21-pregnanes was obtained by feeding 3-14C-mevalonic acid (7) and [1,7,15,22,26-'4C5J-cholesterol (1) (8). These results are consistent with a biosynthetic route via the mevalonic acid pathway.…”

Effects of Mineral Salts, Initial pH and Precursors on Digitoxin Formation by Shoot-forming Cultures ofDigitalis purpureaL. Grown in Liquid Media

“…5). Growth was not repressed by 1 mg or less of progesterone, although 10 Cholesterol. Growth was only slightly affected even at 50 mg of cholesterol per 100 ml of medium, but digitoxin formation was repressed by cholesterol at 0.1 mg or more (Fig.…”

ACTH-Modulated Membrane Guanylate Cyclase Signaling System: Origin and Creation

“…Ignited by the fervor of the author's early findings that a common evolutionary link exists between the generation of plant steroids, cardenolides, and the mammalian steroid hormones (Wickramsinghe et al, 1969 ; Sharma, 1970a , b , c ; Kitabchi et al, 1971a , b ), he decided to decode this link, and thus, entered the field of hormonal signal transduction. Because cholesterol in both generations was the central precursor molecule, it became the subject matter of the author's research for the next 18 years, from 1969 to 1987.…”

“…The basis of the concept was that in both plant and mammalian kingdoms, biosynthetic pathways of the cholesterol formation are identical; they start from the primordial mevalonic acid molecule (Wickramsinghe et al, 1969 ; Sharma, 1970b ; Kitabchi et al, 1971b ). In the evolutionary ladder, a change occurs, however.…”

“…Then, the signal is transmitted selectively to the isolated fasciculate cell of the adrenal gland; the cell using its stored cholesterol synthesized from mevalonic acid transforms it into the steroid hormone and cortisol/corticosterone (Kitabchi et al, 1971b ). In the plant, in contrast, cholesterol is transformed into cardenolides (Wickramsinghe et al, 1969 ; Sharma, 1970a , b , c ). Outstandingly, in both cases, the targeted site of cholesterol is its side chain: cleavage in mammals and rearrangement in plants.…”