LANOSTEROL

Description

Lanosterol occurs naturally in the eyes of mammals and has been shown to dissolve cataracts by revitalizing damaged cataract-causing crystallin proteins. Lanosterol’s amphipathic nature is believed to play a large role in its ability to prevent and reverse cataract formation.

Source

Lanosterol is the first sterol in lipid biosynthetic pathway, which is initially converted by acetyl-CoA. The complex process of lanosterol synthesis involves several enzymes, including 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, squalene epoxidase, and lanosterol synthase (LSS). LSS is a microsomal enzyme that functions as a downstream element in the lanosterol biosynthetic pathway, catalyzing the cyclization of the linear 2,3-monoepoxysqualene to lanosterol.

Function

A cytochrome P450 monooxygenase involved in sterol biosynthesis. Catalyzes 14-alpha demethylation of lanosterol and 24,25-dihydrolanosterol likely through sequential oxidative conversion of 14-alpha methyl group to hydroxymethyl, then to carboxylaldehyde, followed by the formation of the delta 14,15 double bond in the sterol core and concomitant release of formic acid (PubMed:20149798, PubMed:8619637). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase.

Biosynthesis pathway

The lanosterol pathway refers to a segment of the cholesterol biosynthesis pathway comprising twelve enzymes, namely acetyl-CoA acetyltransferase, hydroxymethylglutaryl-CoA synthase, hydroxymethylglutaryl-CoA reductase, mevalonate kinase, phosphomevalonate kinase, diphoshomevalonate decarboxylase, isopentenyl-diphosphate delta isomerase, geranylgeranyl diphosphate synthase, farnesyl diphosphate synthase, squalene synthase, squalene monooxygenase and lanosterol synthase. The lanosterol pathway describes the stages of cholesterol biosynthesis between the conversion of substrates acetyl CoA and acetoacetyl CoA to (S)-3-hydroxy-3-methylglutaryl-CoA, through to the formation of intermediate metabolite lanosterol, the precursor of cholesterol. Metabolites of the lanosterol pathway are either directed to the synthesis of cholesterol and other sterols, or to side branches of the pathway through which they are converted to isoprenoids and other non-sterols.

Description

Lanosterol is a naturally-occurring sterol and biosynthetic precursor of several animal, fungal, and protozoan steroids, including cholesterol and ergosterol. Defects in the processing of lanosterol contribute to a wide variety of disorders, including the formation of cataracts. Similarly, certain fungicides act by blocking lanosterol processing by fungi.

Uses

Lanosterol has been used:

• as a standard in HPLC for the quantification in testis samples
• in S-adenosyl-L-methionine:Δ²⁴-sterol-C-methyltransferase (SMT) assay
• to treat wild-type cells growing in rich medium to know its effects on Sre1 protein

Definition

ChEBI: A tetracyclic triterpenoid that is lanosta-8,24-diene substituted by a beta-hydroxy group at the 3beta position. It is the compound from which all steroids are derived.

General Description

Lanosterol, an amphipathic molecule, that is produced by?lanosterol?synthase (LSS). It is enriched in the lens.

Biochem/physiol Actions

Cholesterol precursor sterol.Lanosterol serves as an endogenous selective modulator of macrophage immunity.

Purification Methods

If very impure, then it should be acetylated, converted to the dibromide acetate [crystallised from EtOAc with slow cooling, m 168-170o, [] D +214o (CHCl3)], de-brominated with Zn dust to give the acetate (below) which is recrystallised from 3-4 parts of Me2CO/MeOH (4:1) and hydrolysed as for stigmasterol (below). Recrystallise it from anhydrous MeOH. Dry it in vacuo over P2O5 for 3hours at 90o. The purity is checked by proton magnetic resonance. The acetate crystallises from MeOH with m 131-133o and [ ] 25D +62o (c 1,CHCl3). [Block & Urech Biochemical Preparations 6 32 1958. van Tamelen et al. J Am Chem Soc 104 6479, 6480 1982, Beilstein 6 III 2880, 6 IV 4188.]