Cholesterol Biosynthesis: A Mechanistic Overview.
Cholesterol is an essential component of cell membranes and the precursor for the synthesis of steroid hormones and bile acids. The synthesis of this molecule occurs partially in a membranous world (especially the last steps), where the enzymes, substrates, and products involved tend to be extremely hydrophobic. The importance of cholesterol has increased in the past half-century because of its association with cardiovascular diseases, which are considered one of the leading causes of death worldwide. In light of the current need for new drugs capable of controlling the levels of cholesterol in the bloodstream, it is important to understand how cholesterol is synthesized in the organism and identify the main enzymes involved in this process. Taking this into account, this review presents a detailed description of several enzymes involved in the biosynthesis of cholesterol. In this regard, the structure and catalytic mechanism of the enzymes involved in cholesterol biosynthesis, from the initial two-carbon acetyl-CoA building block, will be reviewed and their current pharmacological importance discussed. We believe that this review may contribute to a deeper level of understanding of cholesterol metabolism and that it will serve as a useful resource for future studies of the cholesterol biosynthesis pathway.
UCIBO-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto , 4169-007 Porto, Portugal.
Nuno M F S A
NM
Cerqueira
UCIBO-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto , 4169-007 Porto, Portugal.
Eduardo F
EF
Oliveira
UCIBO-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto , 4169-007 Porto, Portugal.
Diana S
DS
Gesto
UCIBO-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto , 4169-007 Porto, Portugal.
Diogo
D
Santos-Martins
UCIBO-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto , 4169-007 Porto, Portugal.
Cátia
C
Moreira
UCIBO-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto , 4169-007 Porto, Portugal.
Hari N
HN
Moorthy
UCIBO-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto , 4169-007 Porto, Portugal.
Maria J
MJ
Ramos
UCIBO-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto , 4169-007 Porto, Portugal.
P A
PA
Fernandes
D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis* / Q000378:metabolism; D004798:Enzymes / Q000378:metabolism; D006801:Humans
D004798:Enzymes; D002784:Cholesterol