Xanthohumol is a
natural product found in the female
inflorescence
An inflorescence is a group or cluster of flowers arranged on a Plant stem, stem that is composed of a main branch or a complicated arrangement of branches. Morphology (biology), Morphologically, it is the modified part of the shoot of sperma ...
s of ''
Humulus lupulus
''Humulus lupulus'', the common hop or hops, is a species of flowering plant in the hemp family Cannabinaceae, native to Europe, western Asia and North America. It is a perennial, herbaceous climbing plant which sends up new shoots in early s ...
'', also known as hops. This compound is also found in
beer
Beer is one of the oldest and the most widely consumed type of alcoholic drink in the world, and the third most popular drink overall after water and tea. It is produced by the brewing and fermentation of starches, mainly derived from ce ...
and belongs to a class of compounds that contribute to the bitterness and flavor of hops.
Xanthohumol is a prenylated
chalconoid, biosynthesized by a type III
polyketide synthase
Polyketides are a class of natural products derived from a precursor molecule consisting of a chain of alternating ketone (or reduced forms of a ketone) and methylene groups: (-CO-CH2-). First studied in the early 20th century, discovery, biosynth ...
(PKS) and subsequent modifying
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
s.
Biosynthesis
Xanthohumol is a prenylated chalconoid derived from a plant type III PKS, and is synthesized in the glandular trichromes of hop cones.
L-Phenylalanine
Phenylalanine (symbol Phe or F) is an essential α-amino acid with the formula . It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amin ...
serves as the starting material, which is converted to
cinnamic acid
Cinnamic acid is an organic compound with the formula C6H5-CH=CH- COOH. It is a white crystalline compound that is slightly soluble in water, and freely soluble in many organic solvents. Classified as an unsaturated carboxylic acid, it occurs na ...
by the PLP-dependent
phenylalanine ammonia lyase
The enzyme phenylalanine ammonia lyase (EC 4.3.1.24) catalyzes the conversion of L-phenylalanine to ammonia and ''trans''-cinnamic acid.:
:L-phenylalanine = ''trans''-cinnamate + NH3
Phenylalanine ammonia lyase (PAL) is the first and committed ...
.
Cinnamic acid is oxidized by
cinnamate-4-hydroxylase and loaded onto
Coenzyme A (CoA) by
4-coumarate CoA ligase to yield
4-hydroxy-cinnamoyl CoA, the starter unit for PKS extension.
This molecule is extended three times with
malonyl CoA
Malonyl-CoA is a coenzyme A derivative of malonic acid.
Functions
It plays a key role in chain elongation in fatty acid biosynthesis and polyketide biosynthesis.
Fatty acid biosynthesis
Malonyl-CoA provides 2-carbon units to fatty acids and commi ...
, cyclized through a
Claisen condensation
The Claisen condensation is a carbon–carbon bond forming reaction that occurs between two esters or one ester and another carbonyl compound in the presence of a strong base, resulting in a β-keto ester or a β-diketone. It is named after Ra ...
, and aromatized through
tautomer
Tautomers () are structural isomers (constitutional isomers) of chemical compounds that readily interconvert.
The chemical reaction interconverting the two is called tautomerization. This conversion commonly results from the relocation of a hyd ...
ization to form
naringenin chalcone
Naringenin chalcone is a common chalconoid (or chalcone, not to be confused with the compound chalcone). It is synthesized from 4-coumaroyl-CoA and malonyl-CoA by chalcone synthase (CHS), a key enzyme in the phenylpropanoid pathway. Naringenin ...
(chalconaringenin).
This intermediate has the potential to form a variety of different products depending on the enzymes that modify the core structure.
In the case of xanthohumol, a
prenyltransferase
Prenyltransferases (PTs) are a class of enzymes that transfer allylic prenyl groups to acceptor molecules. Prenyl transferases commonly refer to isoprenyl diphosphate syntheses (IPPSs). Prenyltransferases are a functional category and include seve ...
called ''Humulus lupulus'' prenyltransferase 1 (HlPT-1) attaches a molecule of
dimethylallyl pyrophosphate
Dimethylallyl pyrophosphate (DMAPP; or alternatively, dimethylallyl diphosphate (DMADP); also isoprenyl pyrophosphate) is an isoprenoid precursor. It is a product of both the mevalonate pathway and the MEP pathway of isoprenoid precursor biosynt ...
from the
DXP pathway.
HlPT-1 has a broad substrate specificity and also participates in making other prenylated flavonoids in the hop plant.
Finally, an
O-methyltransferase methylates a phenol substituent using
S-adenosyl methionine
''S''-Adenosyl methionine (SAM), also known under the commercial names of SAMe, SAM-e, or AdoMet, is a common cosubstrate involved in methyl group transfers, transsulfuration, and aminopropylation. Although these anabolic reactions occur throug ...
.
Total syntheses of xanthohumol and derivatives have been achieved, though extraction from hops remains a primary source.
Beer
In commercial beers, the concentration of xanthohumol ranges from about 2 μg/L – 1.2 mg/L.
During the
brewing process, xanthohumol and other prenylated flavonoids are lost as they are converted to the corresponding
flavanone
The flavanones, a type of flavonoids, are various aromatic, colorless ketones derived from flavone that often occur in plants as glycosides.
List of flavanones
* Blumeatin
* Butin
* Eriodictyol
* Hesperetin
* Hesperidin
* Homoeriodictyol
* ...
s. Different hop varieties and different beers contain varying quantities of xanthohumol.
Research
Xanthohumol is under
basic research
Basic research, also called pure research or fundamental research, is a type of scientific research with the aim of improving scientific theories for better understanding and prediction of natural or other phenomena. In contrast, applied rese ...
for its potential biological properties.
Xanthohumol can be
extracted with pressurized hot water.
[A. Gil-Ramírez, J.A. Mendiola, E. Arranz, A. Ruíz-Rodríguez, G. Reglero, E. Ibáñez, F.R. Marín]
Highly isoxanthohumol enriched hop extract obtained by pressurized hot water extraction (PHWE). Chemical and functional characterization
Innovative Food Science and Emerging Technologies 2012 October, vol 16 Pages 54-60
doi: 10.1016/j.ifset.2012.04.006
See also
*
Isoxanthohumol, the corresponding prenylated flavanone
*
8-Prenylnaringenin, a related prenylflavanoid with anti-estrogenic activity
*
Alpha acid
Alpha acids (α acids) are a class of chemical compounds primarily of importance to the production of beer. They are found in the resin glands of the flowers of the hop plant and are the source of hop bitterness.
Alpha acids may be isomerize ...
s, a class of bitter compounds in hops
*
Myrcene
Myrcene, or β-myrcene, is a monoterpene. A colorless oil, it occurs widely in essential oils. It is produced mainly semi-synthetically from '' Myrcia'', from which it gets its name. It is an intermediate in the production of several fragrances. ...
,
humulene
Humulene, also known as α-humulene or α-caryophyllene, is a naturally occurring monocyclic sesquiterpene (C15H24), containing an 11-membered ring and consisting of 3 isoprene units containing three nonconjugated C=C double bonds, two of them be ...
, and
caryophyllene
Caryophyllene (), more formally (−)-β-caryophyllene, (BCP), is a natural bicyclic sesquiterpene that is a constituent of many essential oils, especially clove oil, the oil from the stems and flowers of ''Syzygium aromaticum'' (cloves), the ess ...
, essential oils in hops
References
{{reflist, 30em
Chalconoids
O-methylated natural phenols
Humulus