Steroidal triterpenes of cholesterol synthesis

Ačimovič, Jure (author), Rozman, Damjana (author)

Cholesterol synthesis is a ubiquitous and housekeeping metabolic pathway that leads to cholesterol, an essential structural component of mammalian cell membranes, required for proper membrane permeability and fluidity. The last part of the pathway involves steroidal triterpenes with cholestane ring structures. It starts by conversion of acyclic squalene into lanosterol, the first sterol intermediate of the pathway, followed by production of 20 structurally very similar steroidal triterpene molecules in over 11 complex enzyme reactions. Due to the structural similarities of sterol intermediates and the broad substrate specificity of the enzymes involved (especially sterol-Δ$^{24}$-reductase; DHCR24) the exact sequence of the reactions between lanosterol and cholesterol remains undefined. This article reviews all hitherto known structures of post-squalene steroidal triterpenes of cholesterol synthesis, their biological roles and the enzymes responsible for their synthesis. Furthermore, it summarises kinetic parameters of enzymes (V$_{max}$ and K$_m$) and sterol intermediate concentrations from various tissues. Due to the complexity of the post-squalene cholesterol synthesis pathway, future studies will require a comprehensive meta-analysis of the pathway to elucidate the exact reaction sequence in different tissues, physiological or disease conditions. A major reason for the standstill of detailed late cholesterol synthesis research was the lack of several steroidal triterpene standards. We aid to this efforts by summarizing commercial and laboratory standards, referring also to chemical syntheses of meiosis-activating sterols.

• Language: English
• Keywords: sterols, steroidal triterpenes, cholesterol synthesis, post-squalene pathway
• Work type: Article
• Typology: 1.02 - Review Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2013
• Number of pages: Str. 4002-4017
• Numbering: Vol. 18, iss. 4
• PID: 20.500.12556/RUL-129498
• UDC: 577
• ISSN on article: 1420-3049
• DOI: 10.3390/molecules18044002
• COBISS.SI-ID: 30538457
• Publication date in RUL: 02.09.2021

Record is a part of a journal

• Title: Molecules
• Shortened title: Molecules
• Publisher: MDPI
• ISSN: 1420-3049
• COBISS.SI-ID: 18462981

Licences

• License: CC BY 3.0, Creative Commons Attribution 3.0 Unported
• Link: https://creativecommons.org/licenses/by/3.0/deed.en
• Description: You are free to reproduce and redistribute the material in any medium or format. You are free to remix, transform, and build upon the material for any purpose, even commercially. You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
• Licensing start date: 04.04.2013

Secondary language

• Language: Slovenian
• Keywords: steroli, steroidni triterpeni, sinteza holesterola

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0104
• Name: Funkcijska genomika in biotehnologija za zdravje

• Funder: ARRS - Slovenian Research Agency
• Project number: J7-4053
• Name: Funkcijska genomika ravnovesja holesterola: vloga lanosterol 14alfa-demetilaze (CYP51) pri razvoju metaboličnih obolenj