Fig. 2: Schematic representation of key steps of the mevalonate (MVA) pathway leading to sterol and non-sterol isoprenoid synthesis. | Oncogenesis

Fig. 2: Schematic representation of key steps of the mevalonate (MVA) pathway leading to sterol and non-sterol isoprenoid synthesis.

From: Lipids in cancer: a global view of the contribution of lipid pathways to metastatic formation and treatment resistance

Fig. 2

MVA is produced from acetyl-CoA, through reactions that are catalyzed by the acetoacetyl-CoA thiolase (Thiolase), HMG-CoA synthase 1 (HMGCS1) and HMGCR enzymes. MVA is converted into farnesyl-pyrophosphate (FPP), which with the geranylgeranyl-PP are responsible of protein prenylation. FPP molecules can also be condensed by the squalene synthase (SQS) to produce squalene. Then, squalene is oxidized and cyclized to lanosterol by the squalene epoxidase (SQLE) and lanosterol synthase (LSS), respectively. Finally, lanosterol is converted to cholesterol by 19 oxygen-based reactions through the Kandutsch-Russell or the Bloch pathway. De novo synthetized cholesterol and diet-derived cholesterol taken up through the LDL receptor (LDLR)-mediated endocytosis can give rise to cholesteryl esters, hydroxycholesterol (HC) or steroid hormones. HMG-CoA 3-Hydroxy-3-methylglutaryl-coenzyme A, ETC electron transport chain, TCA tricarboxylic acid, CE cholesteryl ester, Chol. cholesterol, 22-, 24-, 25- and 27-HC 22-, 24-, 25- and 27-hydroxycholesterol, CH25H Cholesterol 25-hydroxylase, CYP11A1 cytochrome P450 family 11 subfamily A member 1, CYPs cytochrome P450 enzymes, LDL low density lipoprotein. Indirect and direct chemical reactions are illustrated by dotted and solid arrows, respectively.

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