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Vitamin D in Nature: A Product of Synthesis and/or Degradation of Cell Membrane Components

  • Göring Consulting


The review discusses the data on vitamin D accumulation in animals, plants, and other organisms. 7-Dehydrocholesterol (7-DHC) and ergosterol are considered to be the only true precursors of vitamin D, although even vitamin D2 (ergocalciferol) is not fully comparable to vitamin D3 (cholecalciferol) in regard to their functions. These precursors are converted by UV radiation into the corresponding D vitamins. There are a few published reports that this reaction can also occur in the dark or under blue light, which is unexpected and requires explanation. Another unexpected result is conversion of pro-vitamins D (7-DHC and ergosterol) into vitamin D3 and D2 via pre-vitamin D at low temperatures (<16°C) in the lichen Cladonia rangiferina. An extensive survey of literature data leads to the conclusion that vitamin D is synthesized from (1) 7-DHC via lanosterol (D3) in land animals; (2) 7-DHC via cycloartenol (D3) in plants; (3) ergosterol via lanosterol (D2) in fungi; and (4) 7-DHC or ergosterol (D3 or D2) in algae. Vitamin D primarily accumulates in organisms, in which it acts as a pro-hormone, e.g., land animals. It can also be found as a degradation product in many other species, in which spontaneous conversion of some membrane sterols upon UV irradiation leads to the formation of vitamins D3 or D2, even if they are not necessarily needed by the organism. Such products accumulate due to the absence of metabolizing enzymes, e.g., in algae, fungi, or lichens. Other organisms (e.g., zooplankton and fish) receive vitamins D with food; in this case, vitamins D do not seem to carry out biological functions; they are not metabolized but stored in cells. A few exceptions were found: the rainbow trout and at least four plant species that accumulate active hormone calcitriol (but not vitamin D) in relatively high amounts. As a result, these plants are very toxic for grazing animals (cause enzootic calcinosis). In connection with the proposal of some scientists to produce large quantities of vitamin D with the help of plants, the accumulation of calcitriol in some plants is discussed.
At present, the importance of vitamin D should be
considered a global issue [1, 2]. The functions of vitamin
D extend far beyond its participation in the bone tissue
metabolism [3]. The vast majority of people and animals
receive only a small amount of vitamin D (~10% or even
less) with food [3]. In humans, the main source of vitamin
D3is its synthesis in skin from the precursor 7dehydro
cholesterol (7DHC) upon exposure to UV radiation.
Unlike cholecalciferol (vitamin D3), humans and animals
receive ergocalciferol (vitamin D2) exclusively from food.
Therefore, ergocalciferol,in contrast to cholecalciferol,is a
true vitamin for them.
A scheme that is widely used when discussing vitamin
D synthesis was suggested by Holick et al. [4]. This scheme
was primarily developed for vitamin D synthesis in humans.
Further in this paper, we will discuss the problem of vitamin
D formation in a broader sense, since new data have recent
ly appeared in the published literature that should be taken
into consideration. In particular, it was found that vitamin
Ddependent organisms can exist under a wide variety of
conditions, for example, at ambient temperatures below
1516°C and at very low intensity of UV radiation [5, 6].
The stages of calcitriol synthesis are shown in the
scheme. Let us consider in more detail the part of this
scheme that preceeds vitamin D3formation.
It is generally accepted that 7DHC and ergosterol
are two initial compounds in the chain of reactions of
ISSN 00062979, Biochemistry (Moscow), 2018, Vol. 83, No. 11, pp. 13501357. © Pleiades Publishing, Ltd., 2018.
Original Russian Text © H. Göring, 2018, published in Biokhimiya, 2018, Vol. 83, No. 11, pp. 16631672.
Abbreviations: 7DHC, 7dehydrocholesterol; UV, ultraviolet;
vitamin D2, ergocalciferol; vitamin D3, cholecalciferol.
Vitamin D in Nature: A Product of Synthesis
and/or Degradation of Cell Membrane Components
H. Göring1,a
1Göring Consulting, De 12555, Berlin, Germany
aemail: horst
Received June 4, 2018
Revision received July 3, 2018
Abstract—The review discusses the data on vitamin D accumulation in animals, plants, and other organisms. 7Dehydro
cholesterol (7DHC) and ergosterol are considered to be the only true precursors of vitamin D, although even vitamin D2
(ergocalciferol) is not fully comparable to vitamin D3(cholecalciferol) in regard to their functions. These precursors are
converted by UV radiation into the corresponding D vitamins. There are a few published reports that this reaction can also
occur in the dark or under blue light, which is unexpected and requires explanation. Another unexpected result is conver
sion of provitamins D (7DHC and ergosterol) into vitamin D3and D2via previtamin D at low temperatures (<16°C) in
the lichen Cladonia rangiferina. An extensive survey of literature data leads to the conclusion that vitamin D is synthesized
from (1) 7DHC via lanosterol (D3) in land animals; (2) 7DHC via cycloartenol (D3) in plants; (3) ergosterol via lano
sterol (D2) in fungi; and (4) 7DHC or ergosterol (D3or D2) in algae. Vitamin D primarily accumulates in organisms, in
which it acts as a prohormone, e.g., land animals. It can also be found as a degradation product in many other species, in
which spontaneous conversion of some membrane sterols upon UV irradiation leads to the formation of vitamins D3or D2,
even if they are not necessarily needed by the organism. Such products accumulate due to the absence of metabolizing
enzymes, e.g., in algae, fungi, or lichens. Other organisms (e.g., zooplankton and fish) receive vitamins D with food; in this
case, vitamins D do not seem to carry out biological functions; they are not metabolized but stored in cells. A few excep
tions were found: the rainbow trout and at least four plant species that accumulate active hormone calcitriol (but not vita
min D) in relatively high amounts. As a result, these plants are very toxic for grazing animals (cause enzootic calcinosis). In
connection with the proposal of some scientists to produce large quantities of vitamin D with the help of plants, the accu
mulation of calcitriol in some plants is discussed.
DOI: 10.1134/S0006297918110056
Keywords: vitamin D synthesis, UV radiation, vitamin D precursors, vitamin D thermal isomerization, vitamin D accumu
lation, vitamin D degradation product, plant calcitriol
BIOCHEMISTRY (Moscow) Vol. 83 No. 11 2018
vitamin D synthesis. However, if we discuss this issue in
more general terms, i.e., search for the precursors of
compounds that possess the properties or functions of
vitamin D, the range of such precursors becomes much
Firstly, there is a group of other sterols that could be
converted into substances similar to vitamin D in the UV
induced photochemical reaction [7]:
22,23dehydroergosterol vitamin D4;
7dehydrositosterol vitamin D5;
7dehydrostigmasterol vitamin D6;
7dehydrocampesterol vitamin D7.
As early as 1968, the first study was published that
compared distribution and functions of vitamins D4and
D3in rat tissues [8]. Unfortunately, no results were
obtained that would have allowed the representatives of
this group to be considered functionally similar to vita
mins D3or D2. Therefore, there is no reason to consider
the original sterols as vitamin D precursors as well.
Secondly, 7DHC is hydroxylated by CYP11A1 with
the formation of 22(OH)7DHC and 20,22(OH)27
DHC that are further converted into 7dehydropreg
nenolon and, finally, into Δ7steroids. In skin, Δ7
steroids form secosteroids under UV radiation. Their
physiological activity is similar to the activity of some
vitamin D metabolites. For example, 21(OH)pregnacal
ciferol inhibits formation of melanoma cell colonies to
the same extent as 1,25(OH)2D3[9]. At the same time,
these compounds display no typical hormonal effects on
bone metabolism and other organism functions.
Assuming that we are searching for a precursor in the
synthesis of active calcitriol hormone or a functionally simi
lar compound,we can reliably refer only to 7DHC and
In our earlier review, we concluded that “without the
UV part of the solar radiation spectrum, no vitamin D
would be present on the Earth at all!” [3]. This statement
is based on the data of many papers published already in
the first years of studying vitamin D [1013]. It is assumed
that the B ring in the 7DHC molecule can be opened by
the energy of photons (18 mJ/cm2) in the 282310 nm
range, which corresponds to UVB radiation [14, 15].
However, the results of some studies contradict this
view. A new mechanism of vitamin D synthesis in the
Scheme of calcitriol synthesis (based on the study by Chen et al. [4] with modifications)
1) 7DHC (provitamin D) “previtamin D”
2) “previtamin D” vitamin D3
3) vitamin D325(OH)D3(calcidiol)
4) 25(OH)D31,25(OH)2D3(calcitriol)
(Hormone active form)
(Inactive circulating form?)
(At what temperature can thermal isomerization take place?
Is vitamin D3inactive intermediate?)
(Are there other precursors? Is UV radiation necessary?)
BIOCHEMISTRY (Moscow) Vol. 83 No. 11 2018
absence of UV radiation was discovered in cultured
Solanum glaucophyllum cells [16, 17]. In these cells (both
in tissue culture and in suspension), the B ring in 7DHC
was opened in the dark. Unfortunately, the cited studies
did not provide explanation for the observed phenome
Several years ago, the effect of UVB radiation on the
accumulation of vitamin D and its hydroxylated metabo
lites in plants from the Solanaceae family was studied in
special climatic chambers [18]. In these experiments,
control plants were grown at a 16 h light/8 h dark cycle
without UV irradiation. If even a small fraction of UV
were present in the light source, photochemical forma
tion of certain amounts of vitamin D and 25(OH)D
should have been expected. And if not? In the review [19]
published soon after, the authors wrote that “vitamin D3
synthesis without the action of UVB has also been report
Another interesting example is formation of vitamin
D from 7DHC in the skin of rainbow trout
(Oncorhynchus mykiss) under blue light (380480 nm). It
is interesting that in this case as well, 1,25(OH)2D3was
accumulated instead of vitamin D3or 25(OH)D3. It
should also be noted that in trout, calcitriol is synthesized
in the liver and not in kidneys (as in land animals) [20].
Nevertheless, considering a large number of pub
lished works and theoretical considerations, one should
proceed from the assumption that UV radiation is essen
tial for the photochemical reaction of 7DHC and ergo
sterol conversion. Under its action, photolysis of 7DHC
and ergosterol can occur even in a test tube with hexane
[21] or other solvents of lipids. This reaction proceeds
faster by an order of magnitude when the sterols are
embedded in biological membranes. It also takes place
under the sunlight in biological waste (e.g., in feces) or,
for example, in hay [3]. At the same time, the rate of this
process largely depends on already existing conditions
(see below).
The optimal condition for the previtamin D ther
mal isomerization is considered to be at a temperature of
25°C [13, 21]. Such temperature conditions may fully
explain the wide occurrence of vitamin D in nature: in the
skin of warmblooded (homoiothermic) animals, on
land, and in the upper layers of the oceans, reservoirs and
rivers in equatorial areas inhabited by vast amounts of
plankton organisms of various phylogenetic origin. The
membranes of plankton cells contain many different
sterols, including 7DHC and ergosterol.
However, humans and animals also live in colder ter
ritories away from the coasts, for example, in the Arctic
and Subarctic tundra. Although the intensity of UV radi
ation in the farnorth regions is low, it remains sufficient
for the synthesis of vitamin D from sterols [22, 23], espe
cially in summer, when the sun shines for almost 24 h a
Another important question is the role of thermal
isomerization in the process of vitamin D formation from
the previtamin in arctic conditions. According to the
scheme, a temperature of 25°C is required for previta
min D thermal isomerization [13]. However, in this case,
specific conditions of isomerization are important [4]. If
conversion of 50% previtamin D into vitamin D at 37°C
in hexane solution takes 30 h, achieving the same result in
human skin at the same temperature takes only 2.5 h [24,
25]. Not only the equilibrium of this reaction is shifted
toward the vitamin D formation, but the reaction rate is
increased by more than 10 times [25]. The reaction rate
changes significantly in aqueous medium in the presence
of βcyclodextrin [26]. Under these conditions, the reac
tion rate constant for previtamin D conversion into vita
min D, as well as the reaction rate constant for the reverse
reaction, increases more than 40 and 600 times, respec
tively, compared to the reaction in nhexane.
It is known that vitamins D2and D3are accumulat
ed, for example, in the reindeer lichen Cladonia rangiferi
na in the Arctic and Subarctic regions [5, 27], where the
maximum temperature rarely exceeds 16°C (mostly stays
within 510°C in summer). Unfortunately, there are little
data on the rate of vitamin D formation under these con
ditions, when all biological processes occur at extremely
slow rates. The annual growth rate of reindeer lichen is
~15 mm at its best. The vitamin D content in the lichen
depends not only on the rate of its synthesis, but also on
the rate of its metabolism (see the next section).
In some organisms, thermal isomerization of previta
min D into vitamin D occurs at temperatures significantly
below 25
C. Do these organisms possess specific adaptations
or “catalysts” for the thermal isomerization of previtamin D
into vitamin D at low temperatures? Might vitamin D accu
mulation occur due to its lowrate formation in the absence
of metabolization or at its significant slowdown?
It is obvious that the formation of the precursor is a
prerequisite for vitamin D synthesis, since the next stage
of this process is carried out without any contribution
from specific enzymes. Certainly, one can expect that
morphological and anatomical features, as well as intra
cellular compartmentalization of the reaction compo
nents, may influence the rate of formation and the quan
tity of the reaction products. Plants synthesize a large
variety of chemical compounds, but this does not mean
that these compounds may be found in tissues in more or
less significant amounts, since they may be intermediate
BIOCHEMISTRY (Moscow) Vol. 83 No. 11 2018
products in the chains of reactions. On the other hand, if
a compound is consumed with food by an organism lack
ing enzymes for further metabolization of this compound,
it simply accumulates in the cells. Fatsoluble products
accumulate in special fat cells (adipocytes), as vitamin D
does in animals [2830].
To illustrate this, let us consider an organism that is
often mentioned in literature on vitamin D, namely the
planktonic coccolithophore Emiliania huxleyi. This species
of plankton has existed in the Sargasso Sea for over 750
million years [11, 31]. In terms of dry weight, E. huxleyi
contains up to 0.1% ergosterol. Ergosterol is an essential
component of cell membranes of many organisms. If
plankton accidentally enters the upper layers of the ocean,
a certain portion of ergosterol is converted into vitamin D2
by UV radiation at sufficiently high temperatures. This
process occurs without any participation of specific
enzymes. The product of this accidental exposure to UV
radiation does not undergo further metabolization, since
cells do not have the necessary enzymes. In this case,vita
min D2is most likely a product of damage or even degradation
of biological membranes under the action of UV radiation.
Which organisms are capable of vitamin D synthesis
and which organisms accumulate it as a degradation prod
uct? 7DHC and animals. The fact that in the animal
world, 7DHC serves as a precursor for the synthesis of
vitamin D under the action of UV light is generally
accepted. This process takes place in most land animals,
from amphibians to primates [11]. In animals, cholesterol
is formed from lanosterol [32, 33]. At the same time, 7
DHC and cholesterol are also found in many plants,
algae, and cyanobacteria.
7DHC and plants. For a long time, it had been
assumed that only vitamin D2is synthesized in plants.
The synthesis of vitamin D3was discovered later [34]. In
fact, all data demonstrating vitamin D2formation in
plants result from contamination of plant material with
fungal hyphae [3537]. Although plants possess a fairly
high number of sterols, they lack ergosterol and, conse
quently, vitamin D2[38]. In plants, 7DHC is commonly
found in very low concentrations, amounting to only 1
2% of the total content of sterols, although in some
plants, the concentration of 7DHC can be approximate
ly an order of magnitude higher [3944].
Vitamin D3and its metabolites, including calcitriol
(1,25(OH)2D), were found in some plants. The following
plants contain vitamin D3and its metabolites, including
calcitriol, in relatively large amounts: Solanum malacoxy
lon [45], Lycopersicon esculentum [46, 47], S. tuberosum
[33, 46], S. melongena [46], Cucurbita pepo subsp. pepo
convar. giromontina [46], S. glaucophyllum (plants and
cell culture) [16, 17, 48], Nicotiana glauca [33, 49],
Cestrum diurnum [50], and Trisetum flavescens [51, 52]. It
is surprising that some of these plants not only synthesize
vitamin D3, but also accumulate extremely high concen
trations of calcitriol. This primarily applies to four
species: S. malacoxylon [45], S. glaucophyllum [48], C.
diurnum [53], and T. flavescens [51, 52] that prove to be
very dangerous for livestock (cows, sheep, horses, goats,
pigs, and other animals). After eating them, animals fall
ill with hypercalcemia (enzootic calcinosis). This disease
develops as a result of massive intake of vitamin D3, as
well as its active metabolite calcitriol. In Europe, a com
mon cause of hypercalcemia is the yellow oat grass T.
flavescens that typically grows in the European Alps and
the Caucasus [51, 52, 54, 55]. The toxic effect of this
plant is greatly increased after it dries in the sun [56]. In
South America, the toxic effects of vitamin D in some
animals can result from consumption of S. glaucophyllum
and S. malacoxylon of the Solanaceae family. Cestrum
diurnum, which is another Solanaceae species often con
sumed by livestock, grows in North America (USA) [50].
It had been believed before that plants do not contain
vitamin D3. This view was based, on one hand, on a very
low vitamin D3content in most plants [32], and on the
other hand, the use of insufficiently sensitive analytical
methods [19]. In recent years, some authors have come to
the conclusion that cholesterol is characteristic of all
plants, since it is an intermediate product in the synthesis
of steroid glycoalkaloids and phytoecdysteroids [32].
Cycloartenol is considered to be a precursor of 7DHC in
plants [32, 33].
7DHC and algae. Cholesterol was found in green
[57], brown [58] and red [59] algae [19]. Seckbach and
Ikan [59] suggested that cholesterol apparently occurs in
all groups of plants, since it occupies a key position in the
biosynthesis of other steroids.
Ergosterol and fungi. The presence of ergosterol,
often in relatively high concentrations, is characteristic of
all fungi [60]. Ergosterol is a dominant sterol in fruit bod
ies of wild and cultivated fungal species [61]. Moreover,
three other sterols were found in fungi, although in low
concentrations: ergosta7,22dienol, ergosta5,7dienol,
and ergosta7enol. The content of vitamin D2in fungal
fruit bodies could be increased 9 to 14fold by UV irra
diation at 254 nm for 2 h at a distance of ~20 cm. Similar
data were obtained in other laboratories as well [62, 63].
These results demonstrate that fungi possess significant
reserves of ergosterol that could be converted into vitamin
D2by UV radiation. Ergosterol in fungi, like 7DHC in
animals, is synthesized from lanosterol [32].
Ergosterol and algae. Ergosterol was also found in
various species of algae, e.g., Dunaliella tertiolecta [64],
Chlamydomonas reinhardtii [65, 66], Chlorella vulgaris
[67], and Cyanidium caldarium [59, 68] (see also the study
by Bjorn and Wang [6]).
Therefore, the pathways for the synthesis of vitamin D
precursors vary in different groups of organisms:
– land animals – 7DHC from lanosterol;
– higher plants – 7DHC from cycloartenol;
– fungi – ergosterol from lanosterol;
– algae – 7DHC or ergosterol.
BIOCHEMISTRY (Moscow) Vol. 83 No. 11 2018
Up to this moment, we have been mainly interested
in the occurrence of vitamin D and its precursors in vari
ous organisms and only briefly touched the issue of its
accumulation. After all, not all animals require vitamin
D; nevertheless, many of them can accumulate it in sig
nificant amounts.
For example, plankton, which is the first link in the
food chains for many animals, is rich in vitamins D2and
D3. This is particularly typical of plankton in tropical and
subtropical regions. Water circulation in the oceans, in
particular the Gulf Stream current, carries plankton to
distant oceans and seas. In this way, vitamin D is trans
ported, for example, far north, where it performs an
important function in land animals and humans [3].
However, this benefits only coastal regions, as well as
regions permanently covered with ice.
There are small nation populations inhabiting, for
example, the northern regions of Russia (between lati
tudes of 5767°N) [69]. They live relatively far from sea
coasts and are almost completely deprived of vitamin D
sources from the sea plankton. UV radiation in farnorth
ern habitats is clearly insufficient for providing humans
(and animals?) with required amounts of vitamin D.
Their survival depends on the presence of vitamin D in
food. In this case, the initial source of vitamin D is
lichens. Ergosterol and 7DHC, as well as vitamins D2
and D3, were found in the reindeer lichen (Cladonia
rangiferina) that grows in the far north of Russia and other
countries (5770°N) [27, 69]. This symbiotic organism
consisting of a fungus and an alga accumulates vitamins
D2and D3. It forms the first link in a food chain, since it
is the main food source for reindeer in winter. Reindeer
accumulate D vitamins in muscle tissue, giving humans
and predatory animals an opportunity to receive vitamin
D in sufficient quantities.
The concentrations of vitamins D3and D2in the
reindeer lichen are within 67204 and 2255 μg per 100 g
of dry matter, respectively [70]. Moreover, reindeer lichen
also has high ergosterol content. For example, let us
compare the known numbers for certain food products
with a high vitamin D concentration (μg per 100 g of fresh
matter): eggs – 0.412; cheese – 1.25; chicken liver –
1.20; beef liver – 014.1; herring – 2.238.0; trout – 4.2
34.5; fungi – 0.330.0. Reindeer lichen exceeds all the
abovementioned products in its vitamin D content.
A question arises on how can lichens form vitamin
D under these harsh conditions? Calculations demon
strate that even at 70°N, the daily dose of UV radiation in
summer may be quite sufficient for vitamin D biosynthe
sis in lichens [23]. It should be emphasized that even if
the growth rate of reindeer lichen is very low (~320 mm
per year), it grows on vast areas of tundra and light forests
of taiga. In winter, reindeer lichen is the main food
source for reindeer, which consume only the uppermost
part of lichen branches. In addition to reindeer, foxes,
arctic foxes, snow sheep, wolves, lemmings, brown hares,
and some other animals can be found in northern
regions. These regions are sparsely inhabited, but people
began to populate them already ~45,000 years ago [71],
when they moved from NorthEast Siberia to the west
and occupied these places as nomadic hunters or rein
deer shepherds.
There are many organisms in which the concentra
tions of vitamin D and its precursors are very low. Plants
are a good example. They possess these compounds only
as intermediates. In other cases, vitamin D can be accu
mulated in significant amounts, for example, in various
algae that use sterols as building materials for the mem
branes. Such sterols, including UVsensitive cholesterol
and ergosterol, are converted into vitamins D2and D3
under highintensity UV radiation at relatively high tem
peratures of water. The mechanism of formation of these
vitamins is clear; however, it is still unknown whether they
possess any function in these organisms. Most likely, they
do not. From an evolutionary viewpoint, as long as accu
mulated vitamin D does not harm the cells in which it is
formed, its excessive accumulation does not matter for the
natural selection. It may be assumed that similar passive
accumulation occurs in representatives from the protozoa
to aquatic lower vertebrates, as well as in fungi and lichens.
The situation is quite different in land animals,
including humans. These organisms can accumulate
additional amounts of vitamin D as a result of its synthe
sis under UV radiation or consumption with food. In this
case, a portion of vitamin D is accumulated as a reserve
together with other fatsoluble compounds (e.g., vitamins
A, E, and K) in adipocytes.
However, some cases were described that do not fit
into this scheme. For example, the blood levels of vitamin
D in naked mole rats living in the underground colonies
are very low, but at the same time, these animals have a
high content of the Klotho protein, a component of the
antiaging mechanism, whose role in life in the dark is
currently being studied [72]. In his review [72],
Dammann also discusses alterations in the Klotho levels
in another group of nocturnal animals, bats.
Articles with similar titles have appeared in scientific
journals, in which the authors declare the urge for inten
sifying efforts for creating plant mutants capable of vita
min D synthesis and accumulation [19, 38, 73]. Some
researchers believe that plants can also synthesize vitamin
D in the dark [73] (see the section “Vitamin D and UV
radiation”); for this reason, they call for studying the
capacity of underground plant organs to synthesize vita
min D. Other scientists refer to the necessity for UV radi
BIOCHEMISTRY (Moscow) Vol. 83 No. 11 2018
ation in this synthesis and emphasize that vitamin D is
synthesized in animal skin and plant leaves [38].
The idea of using plants as a source of organic vita
min D to meet human needs is tempting. Indeed, plants
with high vitamin D content have been found (four
species so far; see section “7DHC and plants”).
Unfortunately, these plants contain not only vitamin D3,
but even higher concentrations of active calcitriol. While
unicellular organisms accumulate vitamin D as the final
product and land animals accumulate it in the form of
25(OH)D3, in these four plant species, synthesized vita
min D is immediately hydroxylated, forming 25(OH)D3,
which is then converted into calcitriol.
The corresponding hydroxylases in plants are so
active that the entire chain of reactions of calcitriol for
mation occurs without any kind of reverse regulation. The
accumulation of significant amounts of calcitriol indi
cates the absence of its metabolization in plant tissues.
And how can the reaction chain be stopped at the vitamin
D stage? Cultivated plants with high calcitriol content
would be poisonous and unfit for human or animal con
sumption (see section “7DHC and plants”).
Using vitamin D from plant sources is likely to be
complicated. Is it possible that using algal cultures would be
a more promising approach to producing vitamin D
enriched food products?
If we proceed from the scheme, the last two reactions
remain out of our scope. They are rather linked to the
issue of the mechanism of vitamin D action. Neither the
role of vitamin D2, nor that of other D vitamins and their
analogs are discussed in this review. If we consider the
functions of vitamin D in treating rickets and some other
bone diseases, then D2should be obviously placed in the
group of D vitamins [62]. In literature, vitamins D3and
D2are often compared with respect to the accumulation
of the corresponding forms of 25(OH)D [7476]. Some
authors believe that vitamins D2and D3are equally avail
able biologically, regardless of whether they are consumed
with food or taken in capsules [77]. However, no direct
comparison of the effects of vitamins D2and D3has been
carried out [78]. On the other hand, it has been convinc
ingly demonstrated that vitamin D3significantly improves
the overall level of 25(OH)D with much higher efficiency
than vitamin D2[76, 79, 80]. It should be emphasized
that this applies only to the accumulation of 25(OH)D2
and 25(OH)D3. It is not the formation of 25(OH)D2and
25(OH)D3from vitamins D2and D3that is of interest, but
rather the physiological responses caused by the action of
these two forms of vitamin D. Unfortunately, there are
still very little data regarding this issue [81].
Conflict of Interests
The author declares no conflict of interests.
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... Both molecules are formed from distinct precursor sterols (i.e., cholesterol in animals and ergosterol in mushrooms) which are eventually transferred into the corresponding vitamins under ultraviolet (UV) radiation [4][5][6]. Hence, vitamin D is also known as the 'sunshine' vitamin, and levels in foods and humans naturally vary in dependence on UV exposure and lifestyle [5,7,8]. ...
... The third newly formed peak formed during the UV irradiation of vitamin D 2 originated from 5,6-trans vitamin D 2 (7) (verified by a standard). In GC/MS, 5,6-trans vitamin D 2 (7) and c(+)Zt trans vitamin D 2 (6) were converted into pyro-and isopyro-vitamin D 2 (i.e. the same compounds, Content courtesy of Springer Nature, terms of use apply. Rights reserved. ...
Full-text available
Vitamin D 2 is produced from its precursor ergosterol under the impact of ultraviolet (UV) light which is also commercially carried out to increase vitamin D 2 contents in mushrooms (‘Novel Food’). However, this process is accompanied by the formation of various isomers that partly co-elute with the target compound and are currently difficult to analyze. For this reason, vitamin D 2 and ergosterol were irradiated with the goal to generate and characterize various isomeric photoproducts with three analytical methods. High-performance liquid chromatography with ultraviolet detection (HPLC–UV) was accompanied by using a chiral detector (CD) which was serially linked with the UV detector. Applied for the first time in this research area, HPLC-CD chromatograms provided complementary information which was crucial for the identification of several co-elutions that would have been overlooked without this approach. Additional information was derived from gas chromatography with mass spectrometry analysis. Diagnostic fragment ions in the GC/MS spectra allowed to distinguish four classes of tri- ( n = 2), tetra-, and pentacyclic isomer groups. Despite several drawbacks of each of the applied methods, the shared evaluation allowed to characterize more than ten isomeric photoproducts of vitamin D 2 including previtamin D 2 , lumisterol 2, tachysterol 2, trans -vitamin D 2 isomers, and two pentacyclic isomers (suprasterols 2 I and II), which were isolated and characterized by proton magnetic resonance spectroscopy ( ¹ H NMR).
... Vitamin D (calciferol) refers to a group of fat-soluble secosteroids that exists in two forms: vitamin D 2 (ergocalciferol) and vitamin D 3 (cholecalciferol). Vitamin D 2 is derived from plant's ergosterol upon exposure to ultraviolet B (UVB) light [1], whereas vitamin D 3 is derived from 7dehydrocholesterol (7DHC) found in the human and animal skin following exposure also to UVB light [2]. e main exogenous sources of vitamin D 2 are plants, plankton, and fungi [3], whereas the main sources of vitamin D 3 are dairy products, fish, meat, and poultry [4,5]. ...
... Calcidiol is the major circulating form of vitamin D [9], and therefore, its serum concentration can be used to measure the vitamin D status [10]. In the kidney, calcidiol undergoes another hydroxylation process mediated by the 1α-hydroxylase (CYP27B1) enzyme to form calcitriol (1,25(OH) 2 ), which is a fully active hormone that is responsible for most (if not all) of the vitamin D biological actions [6,7]. At tissue levels, vitamin D in its active form (calcitriol) binds to the vitamin D receptor (VDR), which is an intracellular protein, and the vitamin D-VDR complex translocates into the nucleus to bind to target genes and modify the gene expression [11,12]. ...
Full-text available
Vitamin D deficiency is a common health problem worldwide. Despite its known skeletal effects, studies have begun to explore its extra-skeletal effects, that is, in preventing metabolic diseases such as obesity, hyperlipidemia, and diabetes mellitus. The mechanisms by which vitamin D deficiency led to these unfavorable metabolic consequences have been explored. Current evidence indicates that the deficiency of vitamin D could impair the pancreatic β-cell functions, thus compromising its insulin secretion. Besides, vitamin D deficiency could also exacerbate inflammation, oxidative stress, and apoptosis in the pancreas and many organs, which leads to insulin resistance. Together, these will contribute to impairment in glucose homeostasis. This review summarizes the reported metabolic effects of vitamin D, in order to identify its potential use to prevent and overcome metabolic diseases.
... In each case, a precursor molecule ("provitamin") is converted to an intermediary molecule ("previtamin") by exposure to UV radiation (UVB, 280-310 nm), which, in turn, is converted into the vitamin itself by the action of heat (through a process of thermal isomerization). The provitamin molecules for vitamins D 2 and D 3 are ergosterol and 7-dehydrocholesterol (7-DHC), respectively (Cardwell et al., 2018), and the central process in the conversion is the opening of the B ring of the provitamin molecule by the energy of photons in the UVB range (Goring, 2018). Other sterols could also be converted to other vitamin D-like molecules, for example, Take-away • A major health problem today is the human population's vitamin D deficiency. ...
Full-text available
Vitamin D is an important human hormone, known primarily to be involved in the intestinal absorption of calcium and phosphate, but it is also involved in various non‐skeletal processes (molecular, cellular, immune, and neuronal). One of the main health problems nowadays is the vitamin D deficiency of the human population due to lack of sun exposure, with estimates of one billion people worldwide with vitamin D deficiency, and the consequent need for clinical intervention (i.e., prescription of pharmacological vitamin D supplements). An alternative to reduce vitamin D deficiency is to produce good dietary sources of it, a scenario in which the yeast Saccharomyces cerevisiae seems to be a promising alternative. This review focuses on the potential use of yeast as a biological platform to produce vitamin D, summarizing both the biology aspects of vitamin D (synthesis, ecology and evolution, metabolism, and bioequivalence) and the work done to produce it in yeast (both for vitamin D2 and for vitamin D3), highlighting existing challenges and potential solutions. This article is protected by copyright. All rights reserved.
... This is likely due to their clothing and/or cultural behaviours. [8,9] Despite being a well-known manifestation of VDD, osteomalacic myopathy is frequently overlooked in the differential diagnosis of muscle weakness in children, resulting in wasteful referrals, investigations, and treatment delays. [10,11] Our research aims to report our experience with osteomalacic myopathy in children and adolescents, emphasizing its importance in neurology practice. ...
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Aim: To assess the response of Vitamin D therapy in Vitamin D deficiency induced Myopathy in Children and Adolescents Study Design: Cross sectional study Methodology: The demographics, clinical presentation, laboratory findings, and treatment response of children and adolescents with osteomalacic myopathy were studied. Clinical, biochemical, and radiographic evidence was used to diagnose vitamin D deficiency. Vitamin D deficiency was identified as the source of myopathic symptoms after therapy with vitamin D. Results: In the final analysis, the children ranged in age from 21 months to 18 years. Eight children (53.33%) were under the age of six, three (26.66.5%) were between the ages of seven and twelve, and fifteen (20%) were between the ages of thirteen and eighteen. Difficulty climbing stairs was reported by 100 % of participants (n=15), followed by difficulty walking, which was reported by 93.33 % of participants (n=14). In 53.33 % of the participants (n=08), abnormal gait was seen. From 4 weeks to 6 months, patients' responses to treatment was recorded. Conclusion: To summarize, vitamin D deficiency in children can result in myopathic symptoms. Vitamin D therapy has had a fantastic clinical response. All the study participants responded to vitamin D therapy
... Except for mushrooms and egg yolk, fish liver and oily fish from seafood are found to be rich sources of vitamin D (Holick & Michael, 2017;Scurria, 2020). Some edible marine algae were found to have vitamin D2 and D3 (Göring, 2018;Ljubic, 2020). Recommended dietary intake for vitamin D stands at 25 μg/day, which depends on the fish diet, consumption of seaweed quantity, cooking methods. ...
Sea is acknowledged for its unexplored complex small molecules with potential health benefits in the field of nutraceutical research. The unique properties of marine compounds set an important part in our diet that play a major therapeutic role against various human diseases. Seafood including finfish, shellfish, and marine algae are rich in proteins, essential amino acids, omega-3 polyunsaturated fatty acids, carotenoids, vitamins, and minerals. Moreover, the by-products of fish processing industries include shell, bones, intestines, fin, and skin contains valuable bioactive molecules such as fish oils, carotenoids, collagen, gelatin, peptides, chitin, chitosan, glycosaminoglycans, and trace elements. These components possess varying health benefits including cardioprotective, neuroprotective, antioxidant, antiinflammatory, anticancer, antiobesity, anticoagulant, antimicrobial, and immunomodulatory activities. Thus, this chapter presents the currently available information/data of seafood bioactive components and their potential health benefits in human nutrition and health care.
... In addition, marine seaweed are a sustainable source of bioactive lipids with high concentrations of omega-3 fatty acids [73][74][75][76] and vitamin D 3 [77,78], whose beneficial effects in psoriasis patients have been outlined above. ...
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Psoriasis is a chronic inflammatory skin disease. Immunological, genetic, and environmental factors, including diet, play a part in the pathogenesis of psoriasis. Metabolic syndrome or its components are frequent comorbidities in persons with psoriasis. A change of eating habits can improve the quality of life of patients by relieving skin lesions and by reducing the risk of other diseases. A low-energy diet is recommended for patients with excess body weight. Persons suffering from psoriasis should limit the intake of saturated fatty acids and replace them with polyunsaturated fatty acids from the omega-3 family, which have an anti-inflammatory effect. In diet therapy for persons with psoriasis, the introduction of antioxidants such as vitamin A, vitamin C, vitamin E, carotenoids, flavonoids, and selenium is extremely important. Vitamin D supplementation is also recommended. Some authors suggest that alternative diets have a positive effect on the course of psoriasis. These diets include: a gluten-free diet, a vegetarian diet, and a Mediterranean diet. Diet therapy for patients with psoriasis should also be tailored to pharmacological treatment. For instance, folic acid supplementation is introduced in persons taking methotrexate. The purpose of this paper is to discuss in detail the nutritional recommendations for persons with psoriasis.
... First studies on the vitamin D2 content of mushrooms were already performed in the 1930s, but systematic assessments were only started almost 60 years later [49]. Ergosterol is a major compound of the fungal plasma membrane, and it was found that UV-B irradiation increases the vitamin D2 content in mushrooms and yeast [50][51][52]. Commercial utilisation of the method was initiated soon after that discovery, including attempts to gain an intellectual property for specific irradiation methods [53][54][55]. ...
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Vitamin D deficiency due to, e.g., nutritional and life style reasons is a health concern that is gaining increasing attention over the last two decades. Vitamin D3, the most common isoform of vitamin D, is only available in food derived from animal sources. However, mushrooms and yeast are rich in ergosterol. This compound can be converted into vitamin D2 by UV-light, and therefore act as a precursor for vitamin D. Vitamin D2 from UV-irradiated mushrooms has become an alternative source of vitamin D, especially for persons pursuing a vegan diet. UV-irradiated baker´s yeast (Saccharomyces cerevisiae) for the production of fortified yeast-leavened bread and baked goods was approved as a Novel Food Ingredient in the European Union, according to Regulation (EC) No. 258/97. The Scientific Opinion provided by the European Food Safety Authority Panel on Dietetic Products, Nutrition, and Allergies has assessed this Novel Food Ingredient as safe under the intended nutritional use. However, recent findings on the formation of side products during UV-irradiation, e.g., the photoproducts tachysterol and lumisterol which are compounds with no adequate risk assessment performed, have only been marginally considered for this EFSA opinion. Furthermore, proceedings in analytics can provide additional insights, which might open up new perspectives, also regarding the bioavailability and potential health benefits of vitamin D-fortified mushrooms and yeast. Therefore, this review is intended to give an overview on the current status of UV irradiation in mushrooms and yeast in general and provide a detailed assessment on the potential health effects of UV-irradiated baker´s yeast.
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Vitamin D has a well-known role in the calcium homeostasis associated with the maintenance of healthy bones. It increases the efficiency of the intestinal absorption of dietary calcium, reduces calcium losses in urine, and mobilizes calcium stored in the skeleton. However, vitamin D receptors are present ubiquitously in the human body and indeed, vitamin D has a plethora of non-calcemic functions. In contrast to most vitamins, sufficient vitamin D can be synthesized in human skin. However, its production can be markedly decreased due to factors such as clothing, sunscreens, intentional avoidance of the direct sunlight, or the high latitude of the residence. Indeed, more than one billion people worldwide are vitamin D deficient, and the deficiency is frequently undiagnosed. The chronic deficiency is not only associated with rickets/osteomalacia/osteoporosis but it is also linked to a higher risk of hypertension, type 1 diabetes, multiple sclerosis, or cancer. Supplementation of vitamin D may be hence beneficial, but the intake of vitamin D should be under the supervision of health professionals because overdosing leads to intoxication with severe health consequences. For monitoring vitamin D, several analytical methods are employed, and their advantages and disadvantages are discussed in detail in this review.
Vitamin D plays crucial roles in calcium absorption, bone metabolism, and immune, neurological and cardiovascular-related functions. In plants, it plays an important role in the form of D2 (ergocalciferol). Intake of vitamin D and its precursors by livestock varies with the specific forage crop, season, presence of fungal infestation and geographic location. Oral supplementation with vitamin D 3 is highly effective at raising plasma and tissue levels of vitamin D and its metabolites in livestock. The vitamin D 3 content varies in different cuts of meat, with higher levels typically correlated with increased fat content , although the same does not hold true for 25(OH)D 3. The highest vitamin D 3 content in meat is typically found in pork (mean content of 2.5 µg/kg) and chicken (mean of 2.4 µg/kg), followed by beef (mean of 2.2 µg/kg), with lamb containing the least (mean of 1.1 µg/kg). Storage and processing generally have minimal impact on the content of vitamin D or its metabolites in meat, aside from an increase on an as-is basis resulting from moisture loss. Due to their widespread availability and consumption, meat products appear to be a significant source of vitamin D and its hydroxylated forms for much of the global population.
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Siberia is one of the coldest environments on Earth and has great seasonal temperature variation. Long-term settlement in northern Siberia undoubtedly required biological adaptation to severe cold stress, dramatic variation in photoperiod, and limited food resources. In addition, recent archeological studies show that humans first occupied Siberia at least 45,000 years ago; yet our understanding of the demographic history of modern indigenous Siberians remains incomplete. In this study, we use whole-exome sequencing data from the Nganasans and Yakuts to infer the evolutionary history of these two indigenous Siberian populations. Recognizing the complexity of the adaptive process, we designed a model-based test to systematically search for signatures of polygenic selection. Our approach accounts for stochasticity in the demographic process and the hitchhiking effect of classic selective sweeps, as well as potential biases resulting from recombination rate and mutation rate heterogeneity. Our demographic inference shows that the Nganasans and Yakuts diverged ∼12,000 - 13,000 years ago from East-Asian ancestors in a process involving continuous gene flow. Our polygenic selection scan identifies seven candidate gene sets with Siberian-specific signals. Three of these gene sets are related to diet, especially to fat metabolism, consistent with the hypothesis of adaptation to a fat-rich animal diet. Additional testing rejects the effect of hitchhiking and favors a model in which selection yields small allele frequency changes at multiple unlinked genes.
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Vitamin D deficiency is a global concern. Much research has concentrated on the endogenous synthesis of vitamin D in human skin following exposure to ultraviolet-B radiation (UV-B, 280–315 nm). In many regions of the world there is insufficient UV-B radiation during winter months for adequate vitamin D production, and even when there is sufficient UV-B radiation, lifestyles and concerns about the risks of sun exposure may lead to insufficient exposure and to vitamin D deficiency. In these situations, dietary intake of vitamin D from foods or supplements is important for maintaining optimal vitamin D status. Some foods, such as fatty fish and fish liver oils, certain meats, eggs, mushrooms, dairy, and fortified foods, can provide significant amounts of vitamin D when considered cumulatively across the diet. However, little research has focussed on assessing edible plant foods for potential vitamin D content. The biosynthesis of vitamin D in animals, fungi and yeasts is well established; it is less well known that vitamin D is also biosynthesised in plants. Research dates back to the early 1900s, beginning with in vivo experiments showing the anti-rachitic activity of plants consumed by animals with induced rickets, and in vitro experiments using analytical methods with limited sensitivity. The most sensitive, specific and reliable method for measuring vitamin D and its metabolites is by liquid chromatography tandem mass spectrometry (LC-MS/MS). These assays have only recently been customised to allow measurement in foods, including plant materials. This commentary focuses on the current knowledge and research gaps around vitamin D in plants, and the potential of edible plants as an additional source of vitamin D for humans.
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The amount of cholesterol made by many plants is not negligible. Whereas cholesterogenesis in animals was elucidated decades ago, the plant pathway has remained enigmatic. Among other roles, cholesterol is a key precursor for thousands of bioactive plant metabolites, including the well-known Solanum steroidal glycoalkaloids. Integrating tomato transcript and protein co-expression data revealed candidate genes putatively associated with cholesterol biosynthesis. A combination of functional assays including gene silencing, examination of recombinant enzyme activity and yeast mutant complementation suggests the cholesterol pathway comprises 12 enzymes acting in 10 steps. It appears that half of the cholesterogenesis-specific enzymes evolved through gene duplication and divergence from phytosterol biosynthetic enzymes, whereas others act reciprocally in both cholesterol and phytosterol metabolism. Our findings provide a unique example of nature's capacity to exploit existing protein folds and catalytic machineries from primary metabolism to assemble a new, multi-step metabolic pathway. Finally, the engineering of a 'high-cholesterol' model plant underscores the future value of our gene toolbox to produce high-value steroidal compounds via synthetic biology.
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Adipose tissue has long been identified as the major site of vitamin D storage. Recent studies have demonstrated that VDR and vitamin D metabolizing enzymes are expressed in adipocytes. Furthermore, it has been shown that vitamin D regulates adipogenic gene expression as well as adipocyte apoptosis. Vitamin D is active in adipocytes at all levels. It interacts with membrane receptors, adaptor molecules, and nuclear coregulator proteins. Several functions of unliganded nVDR were discovered by studying human samples from patients having hereditary vitamin D resistant rickets, transgenic mice overexpressing the VDR and VDR knockout mice. Through its genomic action, vitamin D participates in the regulation of energy metabolism by controlling the expression of uncoupling proteins. In vitro, vitamin D stimulates lipogenesis and inhibits lipolysis by interacting with mVDR. mVDR is present in caveolae of the plasma membrane and is the same as the classic nVDR. In addition, vitamin D affects directly the expression of the appetite regulating hormone, leptin. Some researchers reported also that vitamin D regulates the expression of the insulin sensitizing hormone, adiponectin. Vitamin D reduced cytokine release and adipose tissue inflammation through the inhibition of NF-κB signaling. Scientific research investigating the role of adipose tissue resident immune cells in the pathogenesis of obesity-associated inflammation is scarce. Obesity is associated with vitamin D deficiency. However there is no scientific evidence to prove that vitamin D deficiency predispose to obesity. Vitamin D supplementation may prevent obesity but it does not lead to weight loss in obese subjects.
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Steroidal glycoalkaloids (SGAs) are cholesterol-derived molecules produced by solanaceous species. They contribute to pathogen defence but are toxic to humans and considered as anti-nutritional compounds. Here we show that GLYCOALKALOID METABOLISM 9 (GAME9), an APETALA2/Ethylene Response Factor, related to regulators of alkaloid production in tobacco and Catharanthus roseus, controls SGA biosynthesis. GAME9 knockdown and overexpression in tomato and potato alters expression of SGAs and upstream mevalonate pathway genes including the cholesterol biosynthesis gene STEROL SIDE CHAIN REDUCTASE 2 (SSR2). Levels of SGAs, C24-alkylsterols and the upstream mevalonate and cholesterol pathways intermediates are modified in these plants. Δ(7)-STEROL-C5(6)-DESATURASE (C5-SD) in the hitherto unresolved cholesterol pathway is a direct target of GAME9. Transactivation and promoter-binding assays show that GAME9 exerts its activity either directly or cooperatively with the SlMYC2 transcription factor as in the case of the C5-SD gene promoter. Our findings provide insight into the regulation of SGA biosynthesis and means for manipulating these metabolites in crops.
Traditionally, the main mammalian models used in aging research have been mice and rats, i.e. short-lived species that obviously lack effective maintenance mechanisms to keep their soma in a functional state for prolonged periods of time. It is doubtful that life-extending mechanisms identified only in such short-lived species adequately reflect the diversity of longevity pathways that have naturally evolved in mammals, or that they have much relevance for long-lived species such as humans. Therefore, some complementary, long-lived mammalian models have been introduced to aging research in the past 15–20 years, particularly naked mole-rats (and to a lesser extent also other mole-rats) and bats. Here, I summarize and compare the most important results regarding various aspects of aging – oxidative stress, molecular homeostasis and repair, and endocrinology – that have been obtained from studies using these new mammalian models of high longevity. I argue that the inclusion of these models was an important step forward, because it drew researchers’ attention to certain oversimplifications of existing aging theories and to several features that appear to be universal components of enhanced longevity in mammals. However, even among mammals with high longevity, considerable variation exists with respect to other candidate mechanisms that also must be taken into account if inadequate generalizations are to be avoided.
Ergosterol and 7-dehydroporiferasterol are the predominant sterols in the membranes of the alga Chlamydomonas reinhardtii Dangeard. Ergosterol is primarily found in most fungi, which produce their end-product sterols by way of the intermediate lanosterol. In contrast, plants rarely make ergosterol and plant sterols are made via the intermediate cycloartenol. The cycloartenol-lanosterol bifurcation has been used as a means to evolutionarily categorize species based on their sterol production. Use of bioinformatics has revealed that the green alga, C. reinhardtii is probably producing sterols using a pathway very similar to that of higher plants. The Chlamydomonas genome was searched for genes that encoded proteins exhibiting high similarity to sterol biosynthetic proteins in the higher plant Arabidopsis thaliana or the yeast Saccharomyces cerevisiae. Genes with the greatest similarity were chosen and annotated. To establish whether these genes were expressed, the presence of their transcripts was determined and quantitative RT-PCR was performed. It was observed that many of the transcripts coordinately increased in abundance after deflagellation, which induces an increase in membrane biosynthesis. This work demonstrates that C. reinhardtii has all of the genes necessary for the biosynthesis of ergosterol and 7-dehydroporiferasterol and that this alga uses the higher plant pathway to make a sterol normally associated with fungi. Evidence is also presented that other organisms commonly known as algae, including chlorophytes, haptophytes, rhodophytes, bacillariophytes, a phaeophyte and a cryptomonad, are likely to utilize the same biosynthetic pathway, making sterols via a cycloartenol intermediate.