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TERM PAPER
OF
ORGANIC CHEMISTRY
Topic
STEROL
The term paper is submitted for the partial fulfillment of the requirement for the degree of (M.Sc Chemistry B.Ed) in the division of
science and Technology University of education,Township campus, Lahore
Submitted by
MADIHA MUMTAZ
ROLL # MCE-716-M08
M.Sc. Chemistry(MORNING)
Session2008-2010
DIVISION OF SCIENCE AND TECHNOLOGYUNIVERSITY OF EDUCATIONTOWNSHIP CAMPUS LAHORE
Session 2008-2010
TABLE OF CONTENTS
Chapter No. Topic page
1 STEROL(INTRODUCTION) 03-09
II CHOLESTROL 10-26
III PHYTOSTEROL 27-33
IV OTHER STEROL 34-39
BIBLIOGRAPHY
CHAPTER-IINTRODUCTION:
Sterols are an important class of organic molecules. They occur naturally in plants,
animals, and fungi, with the most familiar type of animal sterol being cholesterol.
Sterol constitutes a large group of compounds with a broad range of biological activities
and physical properties. The natural occurring sterol usually possess the 1,2-
cyclopentanophenanthrene skeleton with a stereochemistry similar to the trans-syn-trans-
anti-trans-anti configuration at their ring junctions, and have 27 to 30 carbon atom with
an hydroxyl group at C3 and a side chain of at least seven carbon at C17.sterol can
exhibit both nuclear variations. Sterol have been defined as
“Hydroxylated steroids that retain some or all of the carbon atoms of squalene in
the side chain and partition almost completely into an ether layer when shaken with
equal with volumes of water and ether”.
sterols are common in eukaryotic cells but rare in prokaryotes. Without exception,
vertebrates confine their sterol bio synthetic activity to producing cholesterol. Most
invertebrates do not have the enzymatic machinery for sterol biosynthesis and must relay
on an outside supply. Sterols of invertebrates have been found to comprise most complex
mixtures arising through food chains. in plants, cholesterol exists only as a minor
component. Sitosterol and stigmosterol are the most abundant widely distributed plant
sterols, while ergo sterol is the major occurring sterol in fungus and yeast. The plant
sterol are characterized by an additional alkyl group at C-24 on the cholesterol nucleus.
Sterols are also known as steroid alcohols. They are a subgroup of steroids with a
hydroxyl group at the 3-position of the A-ring. They are amphipathic lipids synthesized
from acetyl-coenzyme A via the HMG-CoA reductase pathway. The overall molecule is
quite flat. The hydroxyl group on the A ring is polar. The rest of the aliphatic chain is
non-polar.
These are lipids that do not have a straight chain. They are composed of four fused
carbon rings and a long hydrocarbon side chain. The most familiar example is
cholesterol, which is abundant in animal cells.
Sterols may be found either as free sterols, acylated (sterol esters), alkylated (steryl alkyl
ethers), sulfated (sterol sulfate), or linked to a glycoside moiety (steryl glycosides) which
can be itself acylated (acylated sterol glycosides).
Sterol biosynthesis is nearly ubiquitous among eukaryotes, it is almost completely absent
in prokaryotes. As a result, the presence of diverse steranes (saturated 4-cycle skeleton)
in ancient rocks is used as evidence for eukaryotic evolution 2.7 billion years ago. A
sterol biosynthetic pathway was demonstrated in the proteobacterium, Methylococcus
capsulatus, and in the planctomycete, Gemmata obscuriglobus .
STEROL
Sterols are often isolated in the unsaponifiable fraction of any lipid extract and
determined by various chromatographic procedures (HPLC or GLC).
ROLE IN BIOCHEMISTRY:
Sterols and related compounds play essential roles in the physiology of eukaryotic
organisms. For example, cholesterol forms part of the cellular membrane in animals,
where it affects the cell membrane's fluidity and serves as secondary messenger in
developmental signaling. In humans and other animals, corticosteroids, such as cortisol
act as signaling compounds in cellular communication and general metabolism.
BIOSYNTHESIS OF STEROL
Here is the general scheme for biosynthetic pathway.
COLOUR REACTION:
Determination of sterol usually means determination of unsaturated sterols. sterols by
treatment with strong acid, probably through dehydration and subsequent salt formation,
give numerous colour reactions they are useful for preliminary identification and for
qualitative analysis through colourimetry.
LIEBERMANN- BUCHARD REACTION
A chloroform solution of sterol with concentrated sulphuric acid and acetic anhydride
give green colour.
SALKOWSKI REACTION:
A chloroform solution of cholesterol with concentrated sulphuric acid gives red colour in
the chloroform layer and green fluorescence in the sulphuric acid layer.
ROSENHEIM TEST:
A Chloform solution of sterol with 90% trichloroacetic acid gives blue or pink colour.
LIFSCHUTZ TEST:
The sterol and perbenzoic acid heated together in glacial acetic acid followed by addition
of concentrated sulphuric acid gives an intense blue or green color.
FIESER TEST:
THE STEROL is treated with selenium dioxide in benzene at 20°C. The 5α series gives a
yellow colour while the 5β series does not give any colour.
TORTELLI- JAFFE TEST:
An acetic acid solution of sterol added ta a solution of 2% bromine in chloroform gives a
green colour at the interface.
ZLATKIS TEST
A solution of cholesterol in glacial acetic acid is added ta a solution of ferric chloride in
concentrated sulphuric acid and glacial acetic acid to give a purple colour.this test is used
for the determination of cholesterol in plasma.
CLASSIFICATION OF STEROLS:
Based on occurrence, the sterols are broadly classified as follows:
1. Zoosterol
2. Phytosterols
3. Mycosterol
4. Marine sterol
5. Free sterol
CHAPTER-II
CHOLESTEROL
Cholesterol is a waxy steroid metabolite found in the cell membranes and transported in
the blood plasma of all animals. It is an essential structural component of mammalian cell
membranes, where it is required to establish proper membrane permeability and fluidity.
In addition, cholesterol is an important component for the manufacture of bile
acids, steroid hormones, and several fat-soluble vitamins. Cholesterol is the
principal sterol synthesized by animals, but small quantities are synthesized in
other eukaryotes, such as plants and fungi. It is almost completely absent
among prokaryotes, which include bacteria.
The name cholesterol originates from the Greek chole- (bile) and stereos (solid), and
the chemical suffix -ol for an alcohol, as François Poulletier de la Salle first identified
cholesterol in solid form in gallstones, in 1769. However, it was only in 1815 that
chemist Eugene Chevreul named the compound "cholesterine".
STRUCTURE OF CHOLESTROL
PHYSICAL PROPERTIES:Molecular formula: C27H46OMolar mass: 386.65 g/molAppearance: white crystalline powderDensity: 1.052 g/cm3Melting point: 148–150 °C Boiling point : 360 °C (decomposes)Solubility in water: 0.095 mg/L (30 °C) Solubility: soluble in acetone, benzene, chloroform, ethanol, ether, hexane, isopropyl myristate, methanol
Physiology
Since cholesterol is essential for all animal life, it is primarily synthesized from simpler
substances within the body. However, high levels in blood circulation, depending on how
it is transported within lipoproteins, are strongly associated with progression
of atherosclerosis. For a person of about 68 kg (150 pounds), typical total body cholesterol
synthesis is about 1 g (1,000 mg) per day, and total body content is about 35 g. Typical
daily additional dietary intake, in the United States and societies with similar dietary
patterns, is 200–300 mg. The body compensates for cholesterol intake by reducing the
amount synthesized.
Cholesterol is recycled. It is excreted by the liver via the bile into the digestive tract.
Typically about 50% of the excreted cholesterol is reabsorbed by the small bowel back
into the bloodstream. Intestinal tract absorption is highly selective for cholesterol,
excreting plant stanols and sterols (which promote atherosclerosis progression more than
cholesterol), back into the intestinal lumen for elimination.
CHOLESTEROL IN VERTEBRATES
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. The vertebrate brain is the most cholesterol-rich organ,
containing roughly 25% of the total free cholesterol present in the whole body. Its
fundamental carbon structure is a cyclopentanoperhydrophenanthrene ring also called
sterane. It was the first isolated sterol around 1758 by F.P. 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 RK and
Young FG have designated steroids all compounds chemically related to cholesterol.
Cholesterol is found in high concentrations in animal cell membranes, typical
concentrations (expressed as molar percentage of total lipids) being about 30 mol%,
ranging up to 50mol% in red blood cells and as high as 80 mol% in the ocular lens
membranes (Li LK et al., J Lipid Res 1985, 26, 600). Consequently, cholesterol has
numerous functions in membranes ranging from metabolism, as a precursor to hormones
and vitamins, to providing mechanical strength and a control of the phase behavior of
membranes (Rog T et al., Biochim Biophys Acta 2009, 1788, 97). It became clear that the
key role of cholesterol in the lateral organization of membranes and its free volume
distribution seems to be involved in controlling membrane protein activity and "raft"
formation (review in Barenholz Y, Prog Lipid Res 2002, 41, 1). At the cellular level,
cholesterol may be replaced to some extent by some other sterols with minor
modifications of the side chain (campesterol, -sitosterol) (Xu F et al., PNAS 2005, 102,
14551).
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).
CHOLESTEROL IN PLANTS
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). Cholesterol is also
dominant in most all Rhodophyceae algae, it is the only sterol presesnt in Laurencia
paniculata (Al Easa H et al., Phytochemistry 1995, 39, 373).
Function
1. Cholesterol is required to build and maintain membranes.
2. It regulates membrane fluidity over the range of physiological temperatures.
3. In the structural role, cholesterol reduces the permeability of the plasma
membrane to protons (positive hydrogen ions) and sodium ions.
The hydroxyl group on cholesterol interacts with the polar head groups of
the membrane phospholipids and sphingo lipids, while the bulky steroid and the
hydrocarbon chain are embedded in the membrane, alongside the non polar fatty
acid chain of the other lipids.
4. Within the cell membrane, cholesterol also functions in intracellular transport, cell
signaling and nerve conduction.
5. Cholesterol is essential for the structure and function of
invaginated caveolae and clathrin-coated pits, including caveola-dependent and
clathrin-dependent endocytosis. The role of cholesterol in such endocytosis can be
investigated by using methyl beta cyclodextrin (MβCD) to remove cholesterol
from the plasma membrane. Recently, cholesterol has also been implicated in cell
signaling processes, assisting in the formation of lipid rafts in the plasma
membrane. In many neurons, a myelin sheath, rich in cholesterol, since it is
derived from compacted layers of Schwann cell membrane, provides insulation
for more efficient conduction of impulses.
6. Within cells, cholesterol is the precursor molecule in several biochemical
pathways.
In the liver, cholesterol is converted to bile, which is then stored in
the gallbladder. Bile contains bile salts, which solubilize fats in the
digestive tract and aid in the intestinal absorption of fat molecules as well
as the fat-soluble vitamins, Vitamin A, Vitamin D,Vitamin E, and Vitamin
K.
Cholesterol is an important precursor molecule for the synthesis of
Vitamin D and the steroid hormones, including the adrenal
gland hormones cortisol and aldosterone as well as the sex
hormones progesterone, estrogens, and testosterone, and their derivatives.
7. Some research indicates that cholesterol may act as an antioxidant.
CHOLESTEROL SYNTHESIS:
Hydroxymethylglutaryl-coenzyme A (HMG-CoA) is the precursor for cholesterol
synthesis.
HMG-CoA is also an intermediate on the pathway for synthesis of ketone bodies from
acetyl-CoA. The enzymes for ketone body production are located in the mitochondrial
matrix. HMG-CoA destined for cholesterol synthesis is made by equivalent, but different,
enzymes in the cytosol.
HMG-CoA is formed by condensation of acetyl-CoA and acetoacetyl-CoA, catalyzed by
HMG-CoA Synthase.
HMG-CoA Reductase catalyzes production of mevalonate from HMG-CoA.
The carboxyl group of hydroxymethylglutarate that is in ester linkage to the thiol of
coenzyme A is reduced first to an aldehyde and then to an alcohol.
NADPH serves as reductant in the 2-step reaction.
Mevaldehyde is thought to be an active site intermediate, following the first reduction
and release of CoA.
HMG-CoA Reductase is an integral protein of endoplasmic reticulum membranes. The
catalytic domain of this enzyme remains active following cleavage from the
transmembrane portion of the enzyme.
The HMG-CoA Reductase reaction is rate-limiting for cholesterol synthesis. This enzyme
is highly regulated and the target of pharmaceutical intervention Mevalonate is
phosphorylated by 2 sequential phosphate transfers from ATP, yielding the
pyrophosphate derivative.
Pyrophosphomevolanate Decarboxylase catalyzes ATP-dependent decarboxylation, with
dehydration, to yield isopentenyl pyrophosphate. Isopentenyl pyrophosphate is the first of
several compounds in the pathway that are referred to as isoprenoids, by reference to the
compound isoprene
Isopentenyl Pyrophosphate Isomerase inter-converts isopentenyl pyrophosphate and
dimethylallyl pyrophosphate.
The mechanism involves protonation followed by deprotonation.
Prenyl Transferase catalyzes a series of head-to-tail condensation reactions.
Dimethylallyl pyrophosphate reacts with isopentenyl pyrophosphate to form geranyl
pyrophosphate.
Condensation with another isopentenyl pyrophosphate yields farnesyl pyrophosphate.
Each condensation reaction is thought to involve a reactive carbocation formed as PPi is
eliminated.
Prenyl Transferase (Farnesyl Pyrophosphate Synthase) has been crystallized with the
substrate geranyl pyrophosphate bound at the active site.
Squalene Synthase catalyzes head-to-head condensation of 2 molecules of farnesyl
pyrophosphate, with reduction by NADPH, to yield squalene.
Squalene epoxidase catalyzes oxidation of squalene to form 2,3-oxidosqualene. This
mixed function oxidation requires NADPH as reductant and O2 as oxidant. One atom of
oxygen is incorporated into the substrate (as the epoxide) and the other oxygen atom is
reduced to water. Conversion of lanosterol to cholesterol involves 19 reactions, catalyzed
by enzymes associated with endoplasmic reticulum membranes.
Additional modifications yield the various steroid hormones or vitamin D.
Many of the reactions involved in converting lanosterol to cholesterol and other steroids
are catalyzed by members of the cytochrome P450 enzyme superfamily. The human
genome encodes 57 members of the cytochrome P450 superfamily, with tissue-specific
expression and intracellular localization highly regulated. Some P450 enzymes are
localized in mitochondria. Others are associated with endoplasmic reticulum membranes.
Cytochrome P450 enzymes catalyze various oxidative reactions. Many are mixed
function oxidations (mono-oxygenations), that require O2 as well as a reductant such as
NADPH. One oxygen atom is incorporated into a substrate and the other oxygen atom is
reduced to water.
REACTION OF CHOLESTROL
REACTION OF HYDROXYL GROUP
ACYLATION
OXIDATION
NUCLEOPHILIC DISPLACEMENT
ELIMINATION
EPIMERIZATION
CATALYTIC HYDROGENATION
REACTION OF DOUBLE BOND
ALLYLIC REACTION
STEROID REARRANGMENT
FISSION OF DOUBLE BOND
OXIDATIVE DEGRATION
CHLORINATED CHOLESTEROL :
The myeloperoxidase–H2O2–Cl system can react with the double bond in the 2nd ring of
cholesterol to generate α-chlorohydrins (6-β-chloro-cholestane-( 3β,5α)-diol) and other
chlorinated products (Heinecke JW et al., Biochemistry 1994, 33, 10127). Because
chlorohydrins are quite stable, chlorinated sterols may prove useful as markers for
lipoproteins oxidatively damaged by activated phagocytes which are known to secrete
myeloperoxidase.
Cholesterol α-chlorohydrins
These products were also formed in LDL (Hazen SL et al., 1996) and cell membranes
following exposure to HOCl or the myeloperoxidase system (Carr AC et al., Arch
Biochem Biophys 1996, 332, 63). In cells, the formation of cholesterol chlorohydrins
could be potentially disruptive to cell membranes as it results in cell lysis and death. They
could also be potential biomarkers for oxidative damage associated with
neutrophil/monocyte activation.
CHAPTER-IIIPHYTOSTEROLS
Phytosterols (also called plant sterols) are a group of steroid
alcohols, phytochemicals naturally occurring in plants. 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.
History:
In higher plants, the first sterols were isolated by Hesse O (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.
Chemistry of phytosterol
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
Characteristics:
That phytosterols are more efficient than cholesterol in extending the temperature range
in which membrane-associated biological processes can take place (Beck JG et al.,
FASEB J 2007, 21, 1714). These conclusions are in accordance with the fact that plants
have to face higher temperature variations than 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 250 different types of phytosterols have been reported in plant species.
Representatives of these sterols are campesterol, stigmasterol (in soybean oil) and b-
sitosterol. The last one is present in all plant lipids and is used for steroid synthesis. They
all belong to the group of 4-desmethyl sterols and account for 30%, 3%, and 65%,
respectively, of human dietary phytosterol intake. In brown algae (Phaeophyceae) the
dominant sterol is fucosterol and cholesterol is present only in low amounts. An
important sterol from yeast and ergot is the C28 compound Ergosterol (mycosterol).
Upon irradiation, this sterol gives rise to vitamin D2 (calciferol).
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 account for a substantial portion of total dietary sterols in vertebrates but
they are excluded from the body. Accumulation of other sterol than cholesterol is
prevented at the level of the intestinal epithelium concurrently with a facilitation of
biliary excretion of phytosterols. Phytosterols produce a wide spectrum of biological
activities in animals and humans. They are considered efficient cholesterol-lowering
agents (Trautwein EA et al., Eur J Lipid Sci Technol 2003, 105, 171; Ostlund RE, Lipids
2007, 42, 41). In addition, they produce a wide spectrum of therapeutic effects including
anti-tumor properties.
USES:
As a food additive
As a food ingredient or additive, Phytosterols have cholesterol-lowering properties
(reducing cholesterol absorption in intestines).
Dispute
The status of the safety and efficacy of the use of Phytosterols as a food-additive is
disputed. While recent studies suggest that dietary supplementation of plant sterols can
have a leveling effect on human cholesterol, some studies would appear to indicate that
they are hard on the heart, arteries and blood-vessels, meaning, depending on intake, they
may do more damage to the circulatory system than they alleviate.
Potential benefits
The FDA has approved the following claim for Phytosterols: "Foods containing at least
0.4 gram per serving of plant sterols, eaten twice a day with meals for a daily total intake
of at least 0.8 gram, as part of a diet low in saturated fat and cholesterol, may reduce the
risk of heart disease."
Sterols can reduce cholesterol in human subjects by 10% to 15%.
The mechanism behind Phytosterols and the lowering of cholesterol occurs as follows:
the incorporation of cholesterol into micelles in the gastrointestinal is inhibited,
decreasing the overall amount of cholesterol absorbed. This may in turn help to control
body total cholesterol levels, as well as modify HDL, LDL and TAG levels.
Many margarines, butters, breakfast cereals and spreads are now enriched with
Phytosterols and marketed towards people wishing to lower their cholesterol levels.
Detection of organic matter
Due to its presence in terrestrial plant matter and only rare occurrence in unicellar algae,
β-sitosterol can be used as a biomarker indicating the amount of terrestrially derived
organic matter present in a sample.
Detection of adulteration:
Presence of brassicasterol, together with auxiliary markers α-linolenic acid and erucic
acid, is a marker of adulteration of soybean oil and sunflower with grape seed oil. As
there is no brassicasterol in sunflower and soybean oil, but its concentration in grapeseed
oil is about 1400 mg/kg, the amount of grapeseed oil added can be calculated.
Specific sterols:
The uppermost molecule pictured is β-sitosterol.
By removing carbon 242, campesterol is obtained.
By removing carbons 241 and 242, cholesterol is obtained.
Removing a hydrogen from carbons 22 and 23 yields stigmasterol (stigmasta-
5,22-dien-3β-ol).
Removing carbon 242 and hydrogens from carbons 22 and 23
yields brassicasterol (ergosta-5,22-dien-3β-ol).
Further removal of hydrogens from carbons 7 and 8 from brassicasterol
yields ergosterol(ergosta-5,7,22-trien-3β-ol). Important: Ergosterol is not a plant
sterol. Ergosterol is a component of fungal cell membranes, serving the same
function that cholesterol serves in animal cells.
Saringosterol
a derivative of fucosterol, discovered in several brown algae (Phaeophyta), such as
Lessonia nigrescens and Sargassum ringgoldianum, has been shown to inhibit the growth
of Mycobacterium tuberculosis (Wachter GA et al., J Nat Prod 2001, 64, 1463). This
phytosterol compares well with the tuberculosis drug rifampin, without appreciable
toxicity against mammalian cells, and may be the source for future tuberculosis drugs.
Phytostanols
Phytostanols are a fully-saturated subgroup of Phytosterols (they contain no double
bonds). They are in general produced by hydrogenation of Phytosterols.
These saturated sterols are found in very small amounts in plant products, such as nuts,
seeds and legumes but in higher amounts in tissues of a few cereal species. To improve
their solubility, plant stanols are often combined with a fatty acid ester to produce plant
stanol esters. The most generally found stanol is sitostanol.
FUNCTION
Sterol work by preventing the absorption of cholesterol from the intestines. Plant sterols
are also effective in treating enlarged prostate, gallstone and tuberculosis and cancer. The
FDA recommends at least 1.3 grams of plant sterol and 3.4 grams of plant sterol per day
to lower cholesterol. Plant stanols have similar health benefits. Sterols are available in
capsule form.
SIDE EFFECTS
Side effects may include indigestion, feeling of fullness and gas along with
nausea and diarrhea or constipation. Additionally, there may be a decrease in the
sexual drive of men, along with possible impotence (the inability to have a
sustained erection to satisfy himself and his partner).
Sterol may decrease the absorption of beta-carotene from food and vitamins into
the body. This can be corrected by taking sterols and beta carotene at different
times of the day. Additional side effects that may occur are related to plant sterol
products that may include other dietary supplement or herbs. Read these product
labels to avoid consuming products to which u may allergic.
An allergic reaction is a serious medical emergency, the symptoms of which may
include a rash, hives with itching. There may also be swelling of the face, mouth
or tongue and throat along with wheezing, shortness of breath and difficulty in
breathing
CHAPTER-IVOTHER STEROLS
ERGOSTEROL:Ergosterol is a component of fungal cell membranes, serving the same function that
cholesterol serves in animal cells
STRUCTURE:
PHYSICAL PROPERTIES:
Molecular formula C28H44O
Molar mass: 396.65 g/mol
Exact mass : 396.339216
Melting point 160.0 °C
Boiling point 250.0 °C
Ergosterol (ergosta-5,7,22-trien-3β-ol), a sterol, is a biological precursor (a provitamin)
to vitamin D2. It is turned into viosterol by ultraviolet light, and is then converted into
ergocalciferol, which is a form of vitamin D.
. The presence of ergosterol in fungal cell membranes coupled with its absence in animal
cell membranes makes it a useful target for antifungal drugs. Ergosterol is also present in
the cell membranes of some protists, such as trypanosomes. This is the basis for the use
of some antifungal against West African sleeping sickness.
Amphotericin B is an antifungal drug that targets Ergosterol. It binds physically to
Ergosterol within the membrane , and thus creates a polar pore in fungal membranes.
This causes ions (predominantly potassium and protons) and other molecules to leak out,
which will kill the cell.[3] Amphotericin B has been replaced by safer agents in most
circumstances but is still used, despite its side effects, for life-threatening fungal or
protozoa infections.
Miconazole, Itraconazole, and Clotrimazole work in a different way, inhibiting synthesis
of Ergosterol from lanosterol. Ergosterol is a smaller molecule than lanosterol; it is
synthesized by combining two molecules of farnisyl pyrophosphate, a 15 carbon long
protein into lanosterol which has 30 carbons. Then two carbon groups are clipped off,
making Ergosterol. The " azoles" inhibit one of the enzymes which remove a methyl from
lanosterol, one of the steps between lanosterol and Ergosterol.
USES:
Ergosterol is also used as an indicator of fungal biomass in soil. Though
ergosterol does degrade over time, if kept below freezing in a dark environment,
this degradation can be slowed or even stopped completely.
Research has shown Ergosterol may have anti-tumor properties.
Ergosterol powder is an irritant to skin, eyes, and the respiratory tract. Ingestion
of large amounts can cause hypercalcemia, which (if prolonged) can lead to
calcium salt deposits in the soft tissues, and particularly the kidneys.
LANOSTEROL:Lanosterol is found as a major constituent of the unsaponifiable portion of wool fat
(lanoline) : about 15%. It has been shown that the bacterium (planctomycete), Gemmata
obscuriglobus, is able to synthesized lanosterol and its uncommon isomer, parkeol
(Pearson A et al., PNAS 2003, 100, 15357). No subsequent modifications of these sterols
were observed. Animal tissues contain in addition to cholesterol small amounts of 7-
dehydrocholesterol which, on UV irradiation, is converted to vitamin D3 (cholecalciferol).
DESMOSTEROL Desmosterol has been isolated from chick embryos.
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). Desmosterol and 22-
dehydrocholesterol are present in high concentrations in red algae.
DINOSTEROL:
In microalgae, sterols usually possess C27–C29 skeletons, with differences in alkylation
at C-24 and double bonds in the nucleus (D5, D8, D8(14)) and side chain (D22, D24,
D24(28). Dinoflagellates are unusual in terms of steroid composition, as they often
contain sterols with additional methyl groups C-4 and C-23. For example, dinosterol
(4α,23,24-trimethyl-5 α -cholest- 22E-en-3β-ol) is typically found in dinoflagellates
where it is generally accepted as a reliable biomarker (Boon JJ et al., Nature 1979, 277,
125).
23-Methyl sterols have been also reported in diatoms and their sterane equivalents were
also unambiguously identified in sediments and petroleum from the late Jurassic onwards
(Rampen S et al., Org Geochem 2009, 40, 219).
OXYSTEROL:
An important oxysterol, 24S-Hydroxycholesterol, is an enzymatically oxidized product of
cholesterol mainly synthesized in the brain. It was detected in 1953 in horse brain and
named "cerebrosterol" (Ercoli A et al., J Am Chem Soc 1953, 75, 3284). It was proposed
that this oxysterol could be a biochemical marker for Alzheimer disease (Lütjohann D et
al., J Lipid Res 2000, 41, 195). Furthermore, 24S-Hydroxycholesterol is reported to be
protective against α -amyloid peptide, the amyloidogenic peptide found in plaques in
Alzheimer disease brain (Brown J et al., J Biol Chem 2004, 279, 34674).
Starfishes contain a great number of polar steroids (oxysterols) characterized by
numerous hydroxylations which have no counterpart in the animal kingdom. As an
example, the structure of a 5 α-cholestane-hexaol present in a Far Eastern starfish,
Henricia leviuscula, is given below (Ivanchina NV et al., J Nat Prod 2006, 69, 224).
5 α-Cholestane-hexaol
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.
REFERENCE:
1. CHEMISTRY OF NATURAL PRODUCTS
BY
S.V.BHAT
B.A NAGASAMPAGI
M. SIVAKUMAR
2. www.rpi.edu.biochem.cholestrol synthesis
3. www.cyberlipid.org
4. www.wikkipedia.com( cross references)
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"Do healthy people need to eat plant sterols?". Medical News Today. 2004-11-04. http://www.medicalnewstoday.com/articles/15886.php. Retrieved 2008-12-08.
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