Bilobalide is a biologically active
terpenic tri
lactone
Lactones are cyclic carboxylic esters, containing a 1-oxacycloalkan-2-one structure (), or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring.
Lactones are formed by intramolecular esterification of the co ...
present in ''
Ginkgo biloba
''Ginkgo biloba'', commonly known as ginkgo or gingko ( ), also known as the maidenhair tree, is a species of tree native to China. It is the last living species in the order Ginkgoales, which first appeared over 290 million years ago. Fossils ...
''.
Chemistry
Bilobalide is a main constituent of the terpenoids found in Ginkgo leaves. It also exists in minor amounts in the roots. It is a sesquiterpenoid, i.e. it has a 15-carbon skeleton. Its exact synthesis pathway from
farnesyl pyrophosphate
Farnesyl pyrophosphate (FPP), also known as farnesyl diphosphate (FDP), is an intermediate in the biosynthesis of terpenes and terpenoids such as sterols and carotenoids. It is also used in the synthesis of CoQ (part of the electron transport ch ...
is still unknown.
Biosynthesis
Bilobalide and ginkgolide have similar biosynthetic pathways. Bilobalide is formed by partially degraded ginkgolide. Bilobalide is derived from
geranylgeranyl pyrophosphate
Geranylgeranyl pyrophosphate is an intermediate in the biosynthesis of diterpenes and diterpenoids. It is also the precursor to carotenoids, gibberellins, tocopherols, and chlorophylls.
It is also a precursor to geranylgeranylated proteins, whic ...
(GGPP), which is formed by addition of
farnesyl pyrophosphate
Farnesyl pyrophosphate (FPP), also known as farnesyl diphosphate (FDP), is an intermediate in the biosynthesis of terpenes and terpenoids such as sterols and carotenoids. It is also used in the synthesis of CoQ (part of the electron transport ch ...
(FPP) to an
isopentenyl pyrophosphate
Isopentenyl pyrophosphate (IPP, isopentenyl diphosphate, or IDP) is an isoprenoid precursor. IPP is an intermediate in the classical, HMG-CoA reductase pathway (commonly called the mevalonate pathway) and in the ''non-mevalonate'' MEP pathway of i ...
(IPP) unit to form a C
15 sesquiterpene
Sesquiterpenes are a class of terpenes that consist of three isoprene units and often have the molecular formula C15H24. Like monoterpenes, sesquiterpenes may be cyclic or contain rings, including many unique combinations. Biochemical modifica ...
. Such formation went through the
mevalonate pathway
The mevalonate pathway, also known as the isoprenoid pathway or HMG-CoA reductase pathway is an essential metabolic pathway present in eukaryotes, archaea, and some bacteria. The pathway produces two five-carbon building blocks called isopenteny ...
(MVA) and
methylerythritol phosphate MEP pathway. In order to generate bilobalide, C
20 ginkgolide 13 must form first. To transform from GGPP to abietenyl cation 5, a single bifunctional enzyme
abietadiene synthase
The enzyme abieta-7,13-diene synthase (EC 4.2.3.18) catalyzes the chemical reaction
:(+)-copalyl diphosphate \rightleftharpoons abieta-7,13-diene + diphosphate
This enzyme belongs to the family of lyases, specifically those carbon-oxygen lyases ...
E1 is required. However, due to the complexity of ginkgolide structures for rearrangement, ring cleavage, and formation of lactone rings, diterpene 8 is used to explain instead. Levopimaradiene 6 and abietatriene 7 are precursors for ginkgolide and bilobalide formation. The unusual tert-butyl substituent is formed from A ring cleavage in 9. Bilobalide 13 then formed in loss of carbons through degradation from ginkgolide 12, and lactones are formed from residual carboxyl and alcohol functions. The end product of bilobalide contains sesquiterpenes and three lactones units.
Pharmacology
Bilobalide is important for producing several of the effects of ''Gingko biloba'' extracts, and it has neuroprotective effects,
as well as inducing the liver enzymes CYP3A1 and 1A2,
which may be partially responsible for interactions between gingko and other herbal medicines or pharmaceutical drugs. Bilobalide has recently been found to be a
negative allosteric modulator at the
GABAA and
GABAA-rho receptors.
Of GABA
A, it may possibly be selective for the subunits predominantly implicated in cognitive and memory functioning such as
α1.
See also
*
Ginkgolide
References
External links
*
{{Glycinergics
Sesquiterpene lactones
Oxygen heterocycles
GABAA receptor negative allosteric modulators
GABAA-rho receptor negative allosteric modulators
Glycine receptor antagonists
Tert-butyl compounds
Heterocyclic compounds with 4 rings
Nootropics