Steroidal Triterpenes of Cholesterol Synthesis

Molecules

Jure Ačimovič¹ 

[1] id="af1-molecules-18-04002">Centre for Functional Genomics and Bio-Chips, Faculty of Medicine, Institute of Biochemistry, University of Ljubljana, Zaloška 4, Ljubljana SI-1000, Slovenia; E-Mail: [e-mail]-lj.

关键词: sterols;    steroidal triterpenes;    cholesterol synthesis;    post-squalene pathway;   

DOI  :  10.3390/molecules18044002

来源: mdpi

【 摘 要 】

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-Δ²⁴-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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.