Progesterone metabolism in Digitalis lanata

Bennett, Raymond D.; Sauer, Horst H.; Heftmanń, Erich

doi:10.1016/s0031-9422(00)88203-5

Cited by 43 publications

(5 citation statements)

References 6 publications

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“…Since all Digitalis cardenolides are 5/3H-configured, the administration of 3 should result in the formation of 5/3-pregnanes. However, only small amounts of 5I3-pregnane-3,20-dione (4) and 5/3-pregnan-31'3-ol-20-one (6) have been detected (22,23), which may be best explained by the assumption that the stereospecific 513-reduction of 3 is a rate-limiting step in cardenolide formation; once accomplished the products are rapidly processed and channelled into the cardenolides. In most of the feeding experiments carried out, 5a-pregnanes were the main pregnane products accumulating after the administration of 3 (20, 24,25).…”

Section: Studies With Precursors In Vivomentioning

confidence: 99%

“…Indirect evidence of a favoured route not involving I was provided by studies with a specific inhibitor of 24-alkyl sterol biosynthesis. indicating that the pregnenolone oxidation/double bond migration is a reversible process (22). Since all Digitalis cardenolides are 5/3H-configured, the administration of 3 should result in the formation of 5/3-pregnanes.…”

Section: Studies With Precursors In Vivomentioning

confidence: 99%

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Cardenolide Biosynthesis in Foxglove¹

Kreis¹,

Hensel²,

Stuhlemmer³

1998

Planta Med

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The article reviews the state of knowledge on the biosynthesis of cardenolides in the genus Digitalis. It summarizes studies with labelled and unlabelled precursors leading to the formulation of the putative cardenolide pathway. Alternative pathways of cardenolide biosynthesis are discussed as well. Special emphasis is laid on enzymes involved in either pregnane metabolism or the modification of cardenolides.About 20 enzymes which are probably involved in cardenolide formation have been described "downstream" of cholesterol, including various reductases, oxido-reductases, glycosyl transferases and glycosidases as well as acyl transferases, acyl esterases and P450 enzymes. Evidence is accumulating that cardenolides are not assembled on one straight conveyor belt but instead are formed via a complex multidimensional metabolic grid. For example "fucose-type" cardenolides and "digitoxosetype" cardenolides seem to form via different biosynthetic branches and the "norcholanic acid pathway" identified recently seems to be operative only in the formation of fucosetype cardenolides.

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Section: Studies With Precursors In Vivomentioning

confidence: 99%

Section: Studies With Precursors In Vivomentioning

confidence: 99%

Cardenolide Biosynthesis in Foxglove¹

Kreis¹,

Hensel²,

Stuhlemmer³

1998

Planta Med

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“…This might be due to enhanced consumption of progestogens in the form of PO by 5β‐reduction catalyzed by steroid 5β‐reductase/iridoid synthase‐like enzymes (PRISEs). Exogenously applied PR and PO are partially converted by PRISEs in 5β‐cardenolide‐containing plants (Sauer et al ., 1967; Bennett et al ., 1968; Klein et al ., 2022). PRISE conversion of progesterone is essential for 5β‐cardenolide formation and RNAi‐mediated knockdown reduced 5β‐cardenolides in D. lanata shoots (Klein et al ., 2022).…”

Section: Discussionmentioning

confidence: 99%

Occurrence and conversion of progestogens and androgens are conserved in land plants

Shiko,

Paulmann,

Feistel

et al. 2023

New Phytologist

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Summary Progestogens and androgens have been found in many plants, but little is known about their biosynthesis and the evolution of steroidogenesis in these organisms. Here, we show that the occurrence and biosynthesis of progestogens and androgens are conserved across the viridiplantae lineage. An UHPLC‐ESI‐MS/MS method allowed high‐throughput analysis of the occurrence and chemical conversion of progestogens and androgens in 41 species across the green plant lineage. Dehydroepiandrosterone, testosterone, and 5α‐dihydrotestosterone are plants' most abundant mammalian‐like steroids. Progestogens are converted into 17α‐hydroxyprogesterone and 5α‐pregnane‐3,20‐dione. Androgens are converted into testosterone and 5α‐dihydrotestosterone. 17,20‐Lyases, essential for converting progestogens to androgens, seem to be most effective in monocot species. Our data suggest that the occurrence of progestogens and androgens is highly conserved in plants, and their biosynthesis might favor a route using the Δ4 pathway.

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“…After application of ["4C]progesterone to the leaves of foxglove (Digitalis lanata), labelled compounds were isolated. In addition to a number of cardenolides, 5a-pregnane-3,20-dione, 5,/pregnane-3,20-dione, 5a-pregnan-3,-ol-20-one and A5-pregnen-3f-ol-20-one could be found (Bennett et al, 1968). The importance of the 5a.-pregnanes for cardenolide biosynthesis is not yet established, since no Sacardenolides have been found in Digitalis lanata.…”

Section: Introductionmentioning

confidence: 99%

Characterization and localization of progesterone 5α-reductase from cell cultures of foxglove (Digitalis lanata EHRH)

Wendroth

Seitz

1990

Biochemical Journal

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Progesterone 5 alpha-reductase, which catalyses the reduction of progesterone to 5 alpha-pregnane-3,20-dione, was isolated and characterized from cell cultures of Digitalis lanata (foxglove). Optimum enzyme activity was observed at pH 7.0, and the enzyme had an apparent Km value of 30 microM for its substrate progesterone. The enzyme needs NADPH as reductant, which could not be replaced by NADH. For NADPH, the apparent Km value is 130 microM. The optimum temperature was 40 degrees C; at temperatures below 45 degrees C, the product 5 alpha-pregnane-3,20-dione was reduced by a second reaction to 5 alpha-pregnan-3 beta-ol-20-one. Progesterone 5 alpha-reductase activity was not dependent on bivalent cations. In the presence of EDTA, 0.1 mM-Mn2+ had no influence on enzyme activity, whereas 0.1 mM-Ca2+, -Co2+ and -Zn2+ decreased progesterone 5 alpha-reductase activity. Only 0.1 mM-Mg2+ was slightly stimulatory. EDTA and thiol reagents such as dithiothreitol stimulate progesterone 5 alpha-reductase activity. By means of linear sucrose gradient fractionation of the cellular membranes, progesterone 5 alpha-reductase was found to be located in the endoplasmic reticulum.

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Progesterone metabolism in Digitalis lanata

Cited by 43 publications

References 6 publications

Cardenolide Biosynthesis in Foxglove¹

Cardenolide Biosynthesis in Foxglove¹

Occurrence and conversion of progestogens and androgens are conserved in land plants

Characterization and localization of progesterone 5α-reductase from cell cultures of foxglove (Digitalis lanata EHRH)

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Progesterone metabolism in Digitalis lanata

Cited by 43 publications

References 6 publications

Cardenolide Biosynthesis in Foxglove1

Cardenolide Biosynthesis in Foxglove1

Occurrence and conversion of progestogens and androgens are conserved in land plants

Characterization and localization of progesterone 5α-reductase from cell cultures of foxglove (Digitalis lanata EHRH)

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Cardenolide Biosynthesis in Foxglove¹

Cardenolide Biosynthesis in Foxglove¹