Cholesterol and its relatives possessing the 1,2-cyclopentanoperhydrophenanthrene ring system (Figure ​(Figure1)1) form the sterolome, which comprises a chemical library of more than 1000 natural products found in all forms of eukaryotes and some prokaryotes that serve a myriad of biological functions.1,2 The structural and stereochemical commonality of these compounds derive in large part from the action of oxidosqualene synthases (formerly cyclases) that generate the parent sterol frame. In their 1985 Nobel lecture, Brown and Goldstein stated that “cholesterol is the most highly decorated small molecule in biology”, a comment supported by the many Nobel prizes awarded to individuals who devoted a large part of their lives to research one or more aspects of the chemistry and chemical biology of sterols, their metabolites, or other isoprenoids.2,3



Figure 1

Common tetracyclic steroid frame containing the 1,2-cyclopentanoperhydrophenanthrene ring skeleton.

Biosynthesis of cholesterol and other sterols.

Aims : Phytosterols are a subgroup of the steroids, as an important class of bioorganic molecules,widespread in plants, animals, marines as well as fungi and have similarity to cholesterol in structure. These compounds have a long history of consumption as food or pharmaceutical products, and generally recognized as safe without undesirable side effects.

The Story of Beta-sitosterol-A Review

Material dealing with the chemistry, biochemistry, and biological activities of oxysterols is reviewed for the period 1987-1995. Particular attention is paid to the presence of oxysterols in tissues and foods and to their physiological relevance.

Review of progress in sterol oxidations: 1987–1995

Unlike most animals, insects lack the capacity to synthesize sterols that are required in lipid biostructures, as precursors to important steroid hormones and as regulators of developmental processes. Therefore insects must acquire sterols from their diet. Hundreds of different sterols have been identified and the review starts by documenting the occurrence of sterols in different insect foods. Next we look at the various nutritional and biochemical studies that have been conducted, and organize them according to insect relatedness, which allows insect sterol use and metabolic capabilities to be viewed from an evolutionary perspective. How sterol structure influences insect feeding behavior is examined, and the fate of sterols once they have been ingested, including the processes of absorption and transport, their distribution in different tissues, and their role in reproduction, is detailed. The extent to which sterols may influence ecological outcomes is also considered, especially in phytophagous insects with known sterol metabolic constraints. Finally, mention is made of the potential use of exploiting insect sterol requirements and constraints for pest control, as well as the ability of insects to adapt to the presence of novel sterols in their diet.

Insect Sterol Nutrition and Physiology: A Global Overview

The differences between the biosynthesis of sterols in higher plants and yeast/mammals are believed to originate at the cyclization step of oxidosqualene, which is cyclized to cycloartenol in higher plants and lanosterol in yeast/mammals. Recently, lanosterol synthase genes were identified from dicotyledonous plant species including Arabidopsis, suggesting that higher plants possess dual biosynthetic pathways to phytosterols via lanosterol, and through cycloartenol. To identify the biosynthetic pathway to phytosterol via lanosterol, and to reveal the contributions to phytosterol biosynthesis via each cycloartenol and lanosterol, we performed feeding experiments by using [6-13C2H3]mevalonate with Arabidopsis seedlings. Applying 13C-{1H}{2H} nuclear magnetic resonance (NMR) techniques, the elucidation of deuterium on C-19 behavior of phytosterol provided evidence that small amounts of phytosterol were biosynthesized via lanosterol. The levels of phytosterol increased on overexpression of LAS1, and phytosterols derived from lanosterol were not observed in a LAS1-knockout plant. This is direct evidence to indicate that the biosynthetic pathway for phytosterol via lanosterol exists in plant cells. We designate the biosynthetic pathway to phytosterols via lanosterol “the lanosterol pathway.” LAS1 expression is reported to be induced by the application of jasmonate and is thought to have evolved from an ancestral cycloartenol synthase to a triterpenoid synthase, such as β-amyrin synthase and lupeol synthase. Considering this background, the lanosterol pathway may contribute to the biosynthesis of not only phytosterols, but also steroids as secondary metabolites.

https://www.pnas.org/content/pnas/106/3/725.full.pdf

Robert A. Norton

Papers

Carbon-13 nmr studies on sitosterol biosynthesized from [13C]mevalonates

Environmental and chemical effects on growth, resin and rubber production in guayule tissue cultures

Morphogenetic influences on rubber content and molecular weight in tissue cultures of guayule

(S)-Adenosyl-L-Methionine: _24-Sterol Methyl Transferase: Mechanism, Enzymology, Inhibitors and Physiological Importance