General Information of MET (ID: META00534)
Name Farnesol
Synonyms   Click to Show/Hide Synonyms of This Metabolite
(2-trans,6-trans)-3,7,11-Trimethyldodeca-2,6,10-trien-1-ol; (2E,6E)-3,7,11-Trimethyl-2,6,10-dodecatrien-1-ol; (2E,6E)-Farnesol; (e)-Farnesol; (e,e)-Farnesol; 2-cis,6-trans-Farnesol; 2-trans,6-trans-Farnesol; 3,7,11-Trimethyl-2,6,10-dodecatrien-1-ol; Ditrans,polycis-polyprenol; FCI 119a; Farnesol; Farnesyl alcohol; Nikkosome; all-trans-Farnesol; trans,trans-Farnesol; trans,trans-alpha-Farnesol; trans-Farnesol
Source Endogenous;Yeast Metabolite;Prenol lipids;Food;Toxins/Pollutant;Microbial
Structure Type   Sesquiterpenoids  (Click to Show/Hide the Complete Structure Type Hierarchy)
Lipids and lipid-like molecules
Prenol lipids
Sesquiterpenoids
PubChem CID
445070
HMDB ID
HMDB0004305
Formula
C15H26O
Structure
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3D MOL 2D MOL
  Click to Show/Hide the Molecular/Functional Data (External Links/Property/Function) of This Metabolite
KEGG ID
C06081
ChEBI ID
16619
FooDB ID
FDB014891
ChemSpider ID
392816
METLIN ID
7048
Physicochemical Properties Molecular Weight 222.37 Topological Polar Surface Area 20.2
XlogP 4.8 Complexity 265
Heavy Atom Count 16 Rotatable Bond Count 7
Hydrogen Bond Donor Count 1 Hydrogen Bond Acceptor Count 1
Function
Farnesol is a signaling molecule that is derived from farnesyl diphosphate, an intermediate in the isoprenoid/cholesterol biosynthetic pathway. Farnesol is a 15 carbon isoprenoid alcohol is the corresponding dephosphorylated form of the isoprenoid farnesyl diphosphate. Farnesol has a potential role in controlling the degradation of 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase (EC 1.1.1.34, NADPH-hydroxymethylglutaryl-CoA reductase). The enzyme is stabilized under conditions of cellular sterol depletion (e.g. statin-treated cells) and rapidly degraded in sterol-loaded cells. In mammalian cells, this enhanced degradation is dependent on the presence of both a sterol and a non-sterol derived from the isoprenoid pathway; farnesol, the dephosphorylated form of farnesyl diphosphate, can function as the non-sterol component. Farnesol has been shown to activate the farnesoid receptor (FXR), a nuclear receptor that forms a functional heterodimer with RXR. Thus, dephosphorylation of farnesyl diphosphate, an intermediate in the cholesterol synthetic pathway, might produce an active ligand for the FXR:RXR heterodimer. The physiological ligand for FXR remains to be identified; farnesol, may simply mimic the unidentified natural ligand(s). In addition, exogenous farnesol have an effect on several other physiological processes, including inhibition of phosphatidylcholine biosynthesis, induction of apoptosis, inhibition of cell cycle progression and actin cytoskeletal disorganization. Farnesol cellular availability is an important determinant of vascular tone in animals and humans, and provides a basis for exploring farnesyl metabolism in humans with compromised vascular function as well as for using farnesyl analogues as regulators of arterial tone in vivo. A possible metabolic fate for farnesol is its conversion to farnesoic acid, and then to farnesol-derived dicarboxylic acids (FDDCAs) which would then be excreted in the urine. Farnesol can also be oxidized to a prenyl aldehyde, presumably by an alcohol dehydrogenase (ADH), and that this activity resides in the mitochondrial and peroxisomal. Liver Endoplasmic reticulum and peroxisomal fractions are able to phosphorylate farnesol to Farnesyl diphosphate in a Cytosine triphosphate dependent fashion. Prenol is polymerized by dehydration reactions; when there are at least four isoprene units (n in the above formula is greater than or equal to four), the polymer is called a polyprenol. Polyprenols can contain up to 100 isoprene units (n=100) linked end to end with the hydroxyl group (-OH) remaining at the end. These isoprenoid alcohols are also called terpenols These isoprenoid alcohols are important in the acylation of proteins, carotenoids, and fat-soluble vitamins A, E and K. They are also building blocks for plant oils such as farnesol and geraniol. Prenol is also a building block of cholesterol (built from six isoprene units), and thus of all steroids. Prenol has sedative properities, it is probably GABA receptor allosteric modulator.When the isoprene unit attached to the alcohol is saturated, the compound is referred to as a dolichol. Dolichols are important as glycosyl carriers in the synthesis of polysaccharides.
Regulatory Network
Full List of Protein(s) Regulating This Metabolite
      Transferases (EC 2)
            Squalene synthase (FDFT1) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Mutation of FDFT1
                      Induced Change Farnesol concentration: increase
                      Summary Introduced Variation         Induced Change 
                      Disease Status Lipid metabolism disorders [ICD-11: 5C52]
                      Details It is reported that mutation (patients with variants in FDFT1) of FDFT1 leads to the increase of farnesol levels compared with control group.
References
1 Squalene Synthase Deficiency: Clinical, Biochemical, and Molecular Characterization of a Defect in Cholesterol Biosynthesis. Am J Hum Genet. 2018 Jul 5;103(1):125-130.

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