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Lanosterol is a tetracyclic triterpenoid and is the compound from which all animal and fungal steroids are derived. By contrast, plant steroids are produced via cycloartenol . [ 1 ] In the eyes of vertebrates, lanosterol is a natural constituent, having a role in maintaining health of the lens .
Squalene is a biochemical precursor to both steroids and hopanoids. [12] ... It then undergoes an enzyme-catalysed cyclisation to produce lanosterol, ...
Lanosterol synthase (EC 5.4.99.7) is an oxidosqualene cyclase (OSC) enzyme that converts -2,3-oxidosqualene to a protosterol cation and finally to lanosterol. [5] Lanosterol is a key four-ringed intermediate in cholesterol biosynthesis.
It is formed when squalene is oxidized by the enzyme squalene monooxygenase. 2,3-Oxidosqualene is the substrate of various oxidosqualene cyclases, including lanosterol synthase, which produces lanosterol, a precursor to cholesterol. [1] The stereoisomer (R)-2,3-oxidosqualene is an inhibitor of lanosterol synthase.
Research is being done for other compounds which block different steps in the biosynthesis of cholesterol, including the reaction performed by oxidosqualene cyclase which cyclizes squalene to form lanosterol. [7] Oxidosqualene cyclase, which is downstream of squalene in the pathway, is an attractive target for inhibition.
Squalene monooxygenase (also called squalene epoxidase) is a eukaryotic enzyme that uses NADPH and diatomic oxygen to oxidize squalene to 2,3-oxidosqualene (squalene epoxide). Squalene epoxidase catalyzes the first oxygenation step in sterol biosynthesis and is thought to be one of the rate-limiting enzymes in this pathway. [ 5 ]
Steroids feature a cucurbitane core, although in practice they are biosynthesised from either lanosterol (animals and fungi) or cycloartenol (plants) via the cyclization of squalene. Steroids have two principal biological functions, being either key components of cell membranes or signaling molecules that activate steroid hormone receptors.
Squalene biosynthesis is catalyzed by squalene synthase, which belongs to the squalene/phytoene synthase family. Subsequent epoxidation and cyclization of squalene generate lanosterol, which is the starting point for additional modifications into other steroids (steroidogenesis). [ 65 ]
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