Cargando…
Steroidal Triterpenes of Cholesterol Synthesis
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...
Autores principales: | , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269928/ https://www.ncbi.nlm.nih.gov/pubmed/23558541 http://dx.doi.org/10.3390/molecules18044002 |
_version_ | 1783376581246320640 |
---|---|
author | Ačimovič, Jure Rozman, Damjana |
author_facet | Ačimovič, Jure Rozman, Damjana |
author_sort | Ačimovič, Jure |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6269928 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62699282018-12-14 Steroidal Triterpenes of Cholesterol Synthesis Ačimovič, Jure Rozman, Damjana Molecules Review 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. MDPI 2013-04-04 /pmc/articles/PMC6269928/ /pubmed/23558541 http://dx.doi.org/10.3390/molecules18044002 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Review Ačimovič, Jure Rozman, Damjana Steroidal Triterpenes of Cholesterol Synthesis |
title | Steroidal Triterpenes of Cholesterol Synthesis |
title_full | Steroidal Triterpenes of Cholesterol Synthesis |
title_fullStr | Steroidal Triterpenes of Cholesterol Synthesis |
title_full_unstemmed | Steroidal Triterpenes of Cholesterol Synthesis |
title_short | Steroidal Triterpenes of Cholesterol Synthesis |
title_sort | steroidal triterpenes of cholesterol synthesis |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269928/ https://www.ncbi.nlm.nih.gov/pubmed/23558541 http://dx.doi.org/10.3390/molecules18044002 |
work_keys_str_mv | AT acimovicjure steroidaltriterpenesofcholesterolsynthesis AT rozmandamjana steroidaltriterpenesofcholesterolsynthesis |