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)

Ostlund RE, Racette SB, Stenson WF (1 June 2003). "Inhibition of cholesterol absorption by phytosterol-replete wheat germ compared with phytosterol-depleted wheat germ". Am. J. Clin. Nutr. 77 (6): 1385–9. PMID 12791614. http://www.ajcn.org/cgi/pmidlookup?view=long&pmid=12791614.

"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.

Fahy E, Subramaniam S, Brown HA, et al. (2005). "A comprehensive

classification system for lipids". J. Lipid Res. 46 (5): 839–61.

doi:10.1194/jlr.E400004-JLR200. PMID 15722563.

http://www.jlr.org/cgi/content/full/46/5/839.