Abstract
4,4-Dimethylsterols and 4-methylsterols are sterol biosynthetic intermediates (C4-SBIs) acting as precursors of cholesterol, ergosterol, and phytosterols. Their accumulation caused by genetic lesions or biochemical inhibition causes severe cellular and developmental phenotypes in all organisms. Functional evidence supports their role as meiosis activators or as signaling molecules in mammals or plants. Oxygenated C4-SBIs like 4-carboxysterols act in major biological processes like auxin signaling in plants and immune system development in mammals. It is the purpose of this article to point out important milestones and significant advances in the understanding of the biogenesis and biological activities of C4-SBIs.
Highlights
4,4-Dimethylsterols and 4-methylsterols are sterol biosynthetic intermediates (C4-SBIs) acting as precursors of cholesterol, ergosterol, and phytosterols
The reversibility of the last step has been discussed [141]. These findings demonstrate that a sterol-C4-demethylation process has evolved twice independently and that the bacterial sterol demethylation (Sdm) enzymes are functionally restricted to demethylate at C4β without any further oxidation at C4α, explaining the production of C4-SBIs as pathway end-products in methanotrophs otherwise used as geological biomarkers
These findings demonstrate that a sterol‐C4‐demethylation process has evolved twice independently and that the bacterial Sdm enzymes are functionally restricted to demethylate at C4β without any further oxidation at
Summary
Post-squalene sterol biosynthesis consists in the enzymatic conversion of C30 H50 O steroidal triterpene precursors such as lanosterol or cycloartenol into pathway end-products among which the most popular are cholesterol, ergosterol, poriferasterol, sitosterol, and many others distributed among eukaryotes. The authors suggested that the accumulation of 3-ketosterols, the products of C4D like 22-hydroxy-5β-ergostan-3-one would alter membrane properties, auxin transporter activity and growth and development (Figure 2) [129] This conclusion is in line with possible modification of the sterol composition of membrane microdomains, which are tremendously important in cellular homeostasis and signaling [130]. Phenotypes of such plants were reminiscent of an auxin disrupted homeostasis: experimental evidence supports the function of oxojessic acid as an inhibitor of polar auxin transport [52] Taken together these results point out a novel critical role for C4-SBIs on growth and development that is distinct from the status of sterol end-products or brassinosteroids.
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