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STEROLS JoAnn Guest

Feb 11, 2007 13:59 PST

 

STEROLS

http://www.cyberlipid.org/sterols/ster0003.htm

 

Sterols may be found either as free sterols, acylated (sterol

esters), alkylated (steryl alkyl ethers), sulfated (cholesterol

sulfate), or linked to a glycoside moiety (steryl glycosides) which

can be itself acylated (acylated sterol glycosides).

 

 

 

FREE STEROLS

 

Sterols form an important group among the steroids. Unsaturated

steroids with most of the skeleton of cholestane containing a 3b-

hydroxyl group and an aliphatic side chain of 8 or more carbon atoms

attached to position 17 form the group of sterols.

 

 

 

They are lipids resistant to saponification and are found in an

appreciable quantity in all animal and vegetal tissues. These

unsaponifiable lipids may include one or more of a variety of

molecules belonging to 3-hydroxysteroids, they are C27-C30

crystalline alcohols

(in Greek, stereos, solid). These lipids can be classed as

triterpenes

as they derive from squalene which gives directly by cyclization,

unsaturation and 3b-hydroxylation, lanosterol in animals or

cycloartenol in plants.

 

In the tissues of vertebrates, the main sterol is the C27 alcohol

cholesterol (Greek, chole, bile), particularly abundant in adrenals

(10%, w/w), nervous tissues (2%,w/w), liver (0.2%,w/w) and gall

stones, its fundamental carbon structure being a

cyclopentanoperhydrophenanthrene ring (also called sterane). It was

the first isolated sterol around 1770 by Poulletier de La Salle from

gall stones.

In 1815, it was isolated from the unsaponifiable fraction of

animal fats by M.E. Chevreul who named it cholesterine (Greek,

khole, bile and stereos, solid). The correct formula (C27H46O) was

proposed in 1888 by F. Reinitzer but structural studies from 1900 to

1932, mainly by H.O. Wieland " on the constitution of the bile acids

and related substances " (Nobel Prize Chemistry 1927) and by A.O.R.

Windaus on " the constitution of sterols and their connection with

the vitamins " (Nobel

Prize Chemistry 1928), led to the exact steric representation of

cholesterol. In 1936, Callow and Young have designated steroids all

compounds chemically related to cholesterol.

While it became clear very early that cholesterol plays an important

role in controlling cell membrane permeability by reducing average

fluidity, it appears now that it has a key role in the lateral

organization of membranes and free volume distribution. These two

parameters seem to be involved in controlling membrane protein

activity

and " raft " formation (review in Barenholz Y, Prog Lipid Res 2002,

41,

1).

In addition to these roles, cholesterol can form ester linkages with

a

class of secreted polypeptide signaling molecules encoded by the

hedgehog gene family. These proteins function in several patterning

events during metazoan development (Mann R et al., Biochim Biophys

Acta

2000, 1529, 188).

 

The vertebrate brain is the most cholesterol-rich organ , containing

roughly 25% of the total free cholesterol present in the whole body.

 

 

 

 

 

 

 

 

 

 

 

In late-step synthesis of cholesterol, discrete oxidoreductive

and/or

demethylation reactions occur, which start with the common precursor

lanosterol. It was also found as a major constituent of the

unsaponifiable portion of wool fat (lanoline). Animal tissues

contain in

addition to cholesterol small amounts of 7-dehydrocholesterol which,

on

UV irradiation, is converted to vitamin D3 (cholecalciferol).

Desmosterol (24-dehydrocholesterol), an intermediate between

lanosterol

and cholesterol, has been implicated with myelination processes.

While

high desmosterol levels could be detected in the brain of young

animals

(Paoletti R et al., J Am Oil Chem Soc 1965, 42, 400) no desmosterol

was

found in the brain of adult animals. It is also known as an abundant

membrane component in some mammalian cells, such as spermatozoa and

astrocytes (Lin DS et al., J Lipid Res 1993, 34, 491 - Mutka AL et

al.,

J Biol Chem 2004, 279, 48654). Inability to convert desmosterol to

cholesterol leads to the human disorder desmosterolosis (a severe

developmental defect and cognitive impairment) (Waterham HR et al.,

Am J

Hum Genet 2001, 69, 685).

 

In higher plants, the first sterols were isolated by Hesse (1878)

from

the Calabar beans (Phytostigma venenosum) which coined the term

" phytosterine " . This substance was later named stigmasterol (Windaus

and

Hault, 1906) from the plant genus. The denomination " phytosterol "

was

proposed in 1897 (Thoms H) for all sterols of vegetal origin.

Chemically, these sterols have the same basic structure as

cholesterol

but differences arise from the lateral chain which is modified by

the

addition of one or two supernumerary carbon atoms at C-24 with

either a

or b chirality. The 24-alkyl group is characteristic of all

phytosterols

and is preserved during subsequent steroid metabolism in both fungi

and

plants to give hormones that regulate growth and reproduction in a

manner similar to animals.

 

Most phytosterols are compounds having 28 to 30 carbon atoms and one

or

two carbon-carbon double bonds, typically one in the sterol nucleus

and

sometimes a second in the alkyl side chain.

All phytosterols were shown to derive in plants from cycloartenol

and in

fungi from lanosterol, both direct products of the cyclization of

squalene.

 

 

 

More than 200 different types of phytosterols have been reported in

plant species. Representatives of these sterols are campesterol,

stigmasterol (in soybean oil) and b-sitosterol which is present in

all

plant lipids and is used for steroid synthesis. An important sterol

from

yeast and ergot is the C28 compound ergosterol (mycosterol). Upon

irradiation, this sterol gives rise to vitamin D2 (calciferol).

As ergosterol is a cell membrane component largely restricted to

fungi,

its amount in environmental matrices may be used as an index

molecule

for these micro-organisms in a living biomass (Barajas-Aceves M et

al. J

Microbiol Methods 2002, 50, 227; Charcosset JY et al., Appl Environ

Microbiol 2001, 67, 2051).

 

 

 

 

 

 

 

 

 

 

 

Considerable variability in the concentration of free sterols was

observed among different oils. While concentrations lower than 100

mg/100 g are found in oils from coconut, palm, olive, and avocado,

concentrations between 100 and 200 mg/100 g are found in oils from

peanut, safflower, soybean, borage, cottonseed, and sunflower, and

concentrations between 200 and 400 mg/100 g are found in oils from

sesame, canola, rapeseed, corn, and evening primrose (Phillips KM et

al., J Food Comp Anal 2002, 15, 123).

 

Phytosterols produce a wide spectrum of biological activities in

animals

and humans. They are considered efficient cholesterol-lowering

agents.

In addition, they produce a wide spectrum of therapeutic effects

including anti-tumor properties. Further data on their metabolism

and

potential therapeutic action can be found in a review article (Ling

WH

et al., Life Sci 1995, 57, 195).

The European Commission authorized in 2004 the addition of

phytosterols

and phytostanols in food products with conditions of labeling

including

their amount per 100 g and the statement that the human consumption

of

more than 3 g/day should be avoided .

 

Phytostanols are a fully-saturated subgroup of phytosterols (they

contain no double bonds). They occur in trace levels in many plant

species but in high levels in tissues of only in a few cereal

species.

They are in general produced by hydrogenation of phytosterols.

Stanols often occur in dinoflagellates but are not common in other

marine microalgae. Hence, dinoflagellates are often the major direct

source of 5a(H)-stanols in marine sediments (Robinson N et al.,

Nature

1984, 308, 439).

Fully saturated sterols are also found in animals but are of

bacterial

origin. Thus, the 5b(H)-stanol coprostanol constitutes approximately

60%

of the total sterols in human faeces.

 

While cholesterol was considered to be nearly absent in vegetal

organisms, its presence is now largely accepted in higher plants. It

can

be detected in vegetal oils in a small proportion (up to 5% of the

total

sterols) but remains frequently present in trace amounts. An unusual

relatively high content of cholesterol was described in camelina oil

(about 200 mg per kg) (Shukla VKS et al., JAOCS 2002, 79, 965).

However,

several studies have revealed the existence of cholesterol as a

major

component sterol in chloroplasts, shoots and pollens. Furthermore,

cholesterol has been detected as one of the major sterols in the

surface

lipids of higher plant leaves (rape) where he may amount to about

72% of

the total sterols in that fraction (Noda M et al., Lipids 1988, 23,

439).

 

Although practical, the ancient distinction between zoosterols,

mycosterols and phytosterols is no more used, since the same sterol

may

have different sources, but the appellation phytosterol is actually

more

frequently used.

Sterols are often isolated in the unsaponifiable fraction of any

lipid

extract and determined by various chromatographic procedures (HPLC

or

GLC).

 

Avenasterol can be isolated from oat oil. This sterol was shown to

protect specifically frying oils from oxidation owing to its

ethylidene

group in the side chain (White PJ et al., JAOCS 1986, 63, 525).

 

 

 

 

 

An extensive review on the diversity, analysis, and health-promoting

uses of phytosterols and phytostanols may be consulted with interest

(Moreau RA et al., Prog Lipid Res 2002, 41, 457).

 

 

 

 

 

 

 

STEROL ESTERS

 

 

 

 

If sterols occur in the free state in cellular membranes in intimate

association with phospholipid molecules, they are frequently found

esterified to fatty acids. In animal tissues, especially in the

liver,

adrenals and plasma lipids (more the 70% in circulating

lipoproteins),

cholesterol is esterified by a variety of fatty acids and most

frequently by essential fatty acids, thus forming cholesterol

esters.

Thus, the esterification of cholesterol with arachidonic acid gives

cholesteryl arachidonate. Sterol esters are important but highly

variable components of the yeast cell with values ranging from

traces to

50% of the total lipids.

 

The esterification of free cholesterol within intestinal cells (by

acyl

CoA:cholesterol acyltransferase, ACAT) allows the cholesterol to be

stored as a neutral lipid in cytosolic droplets and in the packing

of

cholesterol into lipoprotein particles for export via the plasma to

liver cells.

 

 

 

 

 

 

The chemical bonding between the sterol and the fatty acid is

hydrolyzed

or transesterified much more slowly than most O-acyl lipids. In

plants,

several sterol esters can be found in cell membranes and seed oils,

such

as ergosteryl, stigmasteryl and b-sitosteryl esters. The relative

importance of esterified sterols depends on the vegetal oil, 50-70%

being found in oils from evening primrose, avocado, rapeseed,

canola,

corn, peanut, and sunflower, 30-50% in oils from borage, olive,

sesame,

coconut, and cottonseed, and less than 30% in oils from safflower,

palm,

and soybean. Thus, a large variation in the content and distribution

of

the sterol fractions between different vegetal oils can be observed

(Verleyen T et al., JAOCS 2002, 79, 117). Variability reflects also

differences in processing of oils and in growing season of the plant

source (Phillips KM et al., J Food Comp Anal 2002, 15, 123).

In addition to variations in quantities, yeast sterol esters have

been

found to vary in both the sterol and fatty acid components. Fatty

acids

have a carbon chain from 12 up to 18 carbon atoms, saturated or

having

one to three double bonds. Investigations have shown than more than

20

different sterols occur in the esterified form.

In addition, cholesterol can form ester linkages with a class of

secreted polypeptide signaling molecules encoded by the hedgehog

gene

family. These proteins function in several patterning events during

metazoan development (Mann R et al., Biochim Biophys Acta 2000,

1529,

188). Observations suggest that cholesterol modifcation of

polypeptides

may be not unique to the Hedgehog proteins.

 

The presence of these esterified forms justifies a previous

saponification if an estimation of the total sterol content is

needed.

 

 

 

 

 

STERYL ALKYL ETHERS

 

Steryl alkyl ethers have been reported to occur only in marine

sediments

up to Cretaceous age. ethers. They were first reported in sediments

from

Walvis Bay (Boon JJ et al., Marine Chem 1979, 7, 117). Mass spectral

characteristics indicate that these steryl alkyl ethers consist of

C27–C29 sterols with 1-2 double bonds, that are ether-bound to C8–C9

alkyl chains. The detailed characterization of the structures of

some of

the dominant sedimentary steryl alkyl ethers have been reported

(Schouten S et al., Org Geochem 2005, 36, 1323). Mass chromatography

revealed that they are mainly composed of C27–C29 steroid moieties

with

one double bond and ether-bound to a C10-C12 alkyl moiety.

One of the most frequent structure (cholest-5-enyl 3b-(3-dodecanyl)

ether) found in Pleistocene Atlantic sediments is shown below.

 

 

 

Based on their occurrence in sediments with a high diatom input, it

was

suggested that yet unknown diatoms should be a direct biological

source.

 

 

 

 

 

 

 

 

STERYL GLYCOSIDES

 

 

 

 

Other complexes are found in plant, the steryl glycosides.

 

 

 

 

 

This family consists of one carbohydrate unit linked to the hydroxyl

group of one sterol molecule.

The sterol moiety was determined to be composed of various sterols:

campesterol, stigmasterol, sitosterol, brassicasterol and

dihydrositosterol. The sugar moiety is composed of glucose, xylose

and

even arabinose (Graminae).

In bacteria, Helicobacter was shown to be particularly rich in

cholesterol glucosides (up to 33% of total lipids), thus suggesting

that

these molecules may be important chemotaxonomic markers for these

species (Haque M et al.,J Bacteriol 1995, 177, 5334).

The presence of cholesterol diglucoside was reported in a procaryote

(Acholeplasma axanthum) (Mayberry WR et al., Biochim Biophys Acta

1983,

752, 434).

 

It was shown that sterol glucoside participates to the synthesis of

cellulose (Peng L et al., Science 2002, 295, 147). This glycolipid

is

used as a substrate to produce higher homologues of the cellobioside

type with b-1,4-linked glucosyl residues. The resulting disaccharide

is

split off and used as primer for further elongation to cellulose.

 

Cholesterol glucuronide was isolated from human liver (Hara A et

al.,

Lipids 1982, 17, 515), its content being about 33 nmol/g wet tissue.

The

authors have isolated this compound from the acidic lipid fraction

and

emphasized that it cannot be distinguished readily from ganglioside

GM4

by TLC. Cholesterol glucuronide is presumably synthesized in the

liver

and some of it enters the bloodstream (where it is present at a

concentration of about 6 mg/ml), the rest being probably eliminated

into

the bile..

 

 

 

 

 

 

 

 

 

 

 

ACYLATED STERYL GLYCOSIDES

 

 

 

 

 

These compounds are formed when a fatty acid is found acylated at

the

primary alcohol group of the carbohydrate unit (glucose or

galactose,

see figure above) in the steryl glycoside molecule (Lepage M, J

Lipid

Res 1964, 5, 587). Thus, 6'-palmitoyl-b-D-glucoside of b-sitosterol

is

the major species (51%) detected in potato tubers while

6'-linoleoyl-b-D- glucoside of b-sitosterol is predominant (47%) in

soybean extracts. In these products, other fatty acids were also

detected (16:1, 18:1, 18:3). More complex molecules were reported in

some aquatic plants (Pistia stratiotes) where sitosterol glycosides

are

acylated with acetyl groups (C2' and C4') beside a stearyl residue

(C6')

on the sugar (Della Greca M et al. Phytochemistry 1991, 30, 2422).

 

In a recent survey of 48 plant sources, it was shown that acylated

steryl glucoside is present at concentrations from 1 to 125 mg per

100 g

fresh weight in all kinds of vegetable parts (fruit, tuber, root,

stem,

leaf, cereals), the acylated form being 2 to 10 times more abundant

that

the non acylated sterol glycoside itself (Sugawara T et al., Lipids

1999, 34, 1231).

 

In a plant (Edgeworthia chrysantha), it was demonstrated the

presence of

two steryl glycosides (sitosterol glucopyranoside acylated with

linoleic

or linolenic acid) which have piscicidal activities (at a

concentration

of 100 ppm they kill Oryzias latipes within about two hours)

(Hashimoto

T et al. Phytochemistry 1991, 30, 2927).

 

 

 

 

 

 

 

CHOLESTEROL SULFATE

 

Sulfate ester of cholesterol occurs in mammalian cells. Thus, in red

blood cells and mainly in skin keratinized layers, a

cholesterol-3-O-sulfate can be detected.

 

 

JoAnn Guest

mrsjo-

www.geocities.com/mrsjoguest/Diets

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