Structure and Function of Biomolecules II Biochemistry ...epgp.inflibnet.ac.in/epgpdata/uploads/epgp_content/S000002BI/P000… · Phosphatidyl moiety, simple glycerol moiety and sphingosine

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Biochemistry Structure and Function of Biomolecules II

Glycolipids and Waxes

Paper : 03 Structure and Function of Biomolecules II Module : 22 Glycolipids and Waxes

Principal Investigator

Dr. Sunil Kumar Khare,Professor

Dept. of Chemistry,

I.I.T. Delhi

Content Writer:

Paper Co-ordinator Dr. M.N.Gupta, Emeritus Professor

Dept. of Biochemical Engg. and

Biotechnology, I.I.T. Delhi

Dr. Sunil Kumar Khare,Professor

Dept. of Chemistry,

I.I.T. Delhi

Dr. M.N.Gupta, Emeritus Professor



Content Reviewer:

Dr. Prashant Mishra, Professor



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Description of Module

Subject Name Biochemistry

Paper Name Structure and Function of biomolecules II

Module Name/Title 22 Glycolipids and Waxes

Dr. Vijaya Khader Dr. MC Varadaraj

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Objectives

To learn about phosphatidyl inositol

To understand the role of inositol derivatives obtained from these in signal transduction

To learn about cerebroside and gangliosides

To learn about waxes: their structure and biological roles

Concept Map

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3. Description

The words glycolipids is unlikely to produce any excitement of the kind, say associated

with rDNA!

Yet, we will see that none of the biological molecules are redundant. We will discuss

how simple glycolipids can give rise to inositol phosphates which are so critical in signal

transduction.

Glycolipids again are diverse in structure and function. Both glycol- and lipid

components contribute to this diversity.

Phosphatidyl moiety, simple glycerol moiety and sphingosine are different lipid

components. The carbohydrate part can be a single sugar, disaccharide, trisaccharide or

oligosaccharide.

Apart from the usual monosaccharides, glycolipids also contain glucosamine and

galactosamine units. Sialic acids are also found in glycosphingolipids called gangliosides.

Finally, we will also look at the waxes and their diverse functions.

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Figure 1

The simplest glycolipids are those that contain inositol. The two isomeric inositols are

meso-inositol and scyllitol. Meso-inositol is more commonly called myo-inositol.

This compound is widely distributed in both plants and animals. It was found in boar

semen at the concentration of 1 g/ 100 mL. Scyllitol has been detected in dog fish liver

and cartilage as well as in many plants. These compounds have been known for a long

time since the days of Emil Fischer (1940s).

Myo-inositol is also found in microorganisms. Conversion of glucose to myo-inositol in

yeast was shown way back in 1957 and its catabolism in Acetobacter was also

investigated around the same time.

Figure 2

Phosphatidyl inositols also have been known for a long time. These were found in animal

tissues, plant sources such as wheatgerm and soybean and in bacteria in the period 1949-

1960.

These were earlier classified in terms of inositol derivatives which were obtained upon

their hydrolysis. Inositol monophosphate or diphosphoinositols were obtained from these

lipids. Some also contained galactose and arabinose as well.

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Figure 3

Phosphatidyl inositol 4,5-bisphosphate is a phospholipid found in biomembranes. It is

formed from phosphatidyl inositol which in turn arises from CDP-diacylglycerol and

inositol.

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Figure 4

This bisphosphate PIP2 is involved in a major signal transduction mechanism. This

pathway is initiated by activation of an enzyme which is a phospholipase C and

specifically called polyphosphoinositide diesterase or simply phosphoinositidase.

This enzyme is activated in response to a hormone like serotonin binding to cellular

receptor. The enzyme action liberates inositol 1,4,5-triphosphate (IP3) and diacyl

glycerol.

IP3 has a short life of only few seconds due to phosphatases stripping off all the

phosphate and producing inositol. Alternatively, IP3 can also be further phosphorylated to

1,3,4,5-tetrakisphosphate (IP4) which then generates another isomer of original IP3. This

isomer generated by a phosphatase is inositol 1,3,4-triphosphate.

Inositol 1,3,4-triphosphate is also converted to inositol by a phosphatase. This

phosphatase is strongly inhibited by Li+ at a mM concentration. It is believed that

therapeutic benefit of Li+ in the treatment of manic depression disorders is due to its

inhibition of this phosphatase.

PIP2 generally has Arachidonate at C-2 position of glycerol. We have already learnt

about the importance of this C20 PUFA as a precursor of eicosanoids prostaglandins and

thromboxanes.

Table 1

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Phosphoinositide cascade of signal transduction in fact mediates diverse metabolic

processes. This is as varied as glycogenolysis in liver cells to visual transduction in

invertebrate photoreceptors.

It was Michael Berridge who discovered that IP3 is responsible for a quick release of Ca2+

from its intracellular stores. These stores are in endoplasmic reticulum, smooth muscle

cells and sarcoplasmic reticulum.

It is this Ca2+

which is now present in the cytosol which triggers various processes like

glycogenolysis and smooth muscle contraction.

IP3 at submicromolar concentration opens Ca-channels in the endoplasmic and

sarcoplasmic reticulums. This is how the quick rise in cytoplasmic Ca2+

concentration

happens.

Ca2+

in turn is an important intracellular messanger for many biological processes. Its

transport systems ensure that most of the times Ca2+

concentration in cytosol is ~0.1 μM.

The extracellular Ca2+

concentration is much higher.

It is necessary that cells keep Ca2+

concentrations low. From our studies of metabolism,

we do know that many phosphate esters play an important role there. Pi is an important

specie. Given the low solubility product of calcium phosphate, it will be undesirable to

have high Ca2+

concentration in the cytosol.

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The considerable difference in normal intracellular and extracellular concentrations

makes it possible to quickly increase the cytosolic [Ca2+

] once the Ca channel is opened

in response to IP3 presence.

We see here how biology exploits a simple chemistry concept of solubility product to

design finely controlled metabolic processes.

We also see that an inorganic specie Ca2+

is extremely important and dictates functions of

more complicated molecules and processes!

Ca2+

can co-ordinate with multiple ligands. Asp and Glu side chains and even peptide

bond carbonyls are good ligands via their oxygen. So, it binds protein very well. In fact,

eukaryotic cells keep a control on [Ca2+

] by sensing it via Calmodulin: a [Ca2+

] detector.

Plant Glycosyl Glycerides

Figure 5

Plants contain glycosyl glycerides. These are generally mono- or di- galactosyl

derivatives of diglycerides.

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Α-D-galactosyl (1→6) β-D-galactosyl diglyceride is a glycolipid found in chloroplasts.

These glycosyl diglycerides of leaves are rich in linolenic acid. Hence, these green leaves

are a good source of this PUFA.

Figure 6

A sulpholipid found widely distributed in plant chloroplasts is a sulphonic acid derivative

of 6-deoxyglucosyl diglyceride. Apart from plant chloroplasts, this glycolipid is also

present in chromatophores of photosynthetic bacteria. This indicates its importance in

photosynthesis.

Some simple compounds formed from sugars and glycerols are also known. As these are

soluble in organic solvents, these can be classified as glycolipids. Alternatively, these

may be viewed as carbohydrate derivatives.

Red marine algae Irideae laminarioides contain α-D-galactopyranosyl-2-glycerol. Wheat

flour contains β-D-galactopyranosyl-1-glycerol. Please note that fatty acids are absent in

these simple glycolipids.

Let us now switch over to the discussion of a more well known class of glycolipids.

Just like glycerol backbone produces diverse kinds of lipids, many lipids are produced

which use sphingosine as a basic scaffold.

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Sphingosine itself is produced from palmitoyl CoA and serve as precursors. These

molecules condense to produce dihydrosphingosine. A dehydrogenase action introduces

the double bond to produce sphingosine.

Figure 7: Ceramide is the precursor of sphingomyelin and of gangliosides

Some important classes of glycolipids are formed from N-acyl sphingosine which is more

commonly called ceramide. These glycolipids are sphingomyelins, cerebrosides and

gangliosides.

In cerebrosides, glucose or galactose is bonded to terminal -OH of ceramide. This

synthesis occurs by UDP-sugars acting as the sugar donor. Please note that wherever

sugars are added to a preexisting compound in biochemistry UDP-sugars often act as

sugar donors.

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Figure 8

The cerebrosides of the neural tissues (in plasma membranes of their cells) generally

have galactose. The corresponding cerebrosides in non neural tissues have glucose. The

terms galactolipds/glucolipids or galactocerebrosides/glucocerebrosides have been

sometimes used.

With the amino group of sphingosine already acylated in ceramide, the cerebrosides have

no charge at pH 7 and are called neutral glycolipids. The other glycosphingolipids which

have two or more sugars, generally, D-glucose, D-galactose or N-acetylgalactosamine are

called globosides.

Cytolipin H is a ceramide lactoside. Cytolipin K is a globoside identified in kidney and it

turned out to be abundantly present in the human erythrocyte stroma. The sugars present

are 2 galactose molecules, glucose and N-acetylglucosamine linked to ceramide.

The nature of fatty acids in the ceramide portion of the cerebroside is also the source of

their structural diversity. The cerebroside kerasin contains C24 saturated fatty acid

lignoceric acid. Another cerebroside phrenosin contains cerebronic acid which is the 2-

hydroxy derivative of lignoceric acid.

Brain white matter contains galactocerebrosides which are rich in sulphate ester analog of

phrenosin with C-3 of the galactose esterified. Such sulfate esters have been sometime

referred to as sulfatides.

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Figure 9: Structure of Ganglioside

The glycosphingolipids found in the nerve tissues and spleen are gangliosides.

Structurally, gangliosides have oligosaccharide chain (rather than couple of sugar/sugar

derivatives as in cerebrosides) attached to the ceramide.

Figure 10

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Other characteristic features of the sugar composition of gangliosides is that the

oligosaccharide chain contains at least one N-acetyl glucosamine or N-acetyl

galactosamine. Also, at least one molecule of N-acetyl neuraminic acid (NAN) is

present.

Gangliosides are formed by the stepwise addition of sugars to the cerebroside. The N-

acetyl neuraminic acid is added, though with the CMP derivative acting as its donor.

In gangliosides of erythrocytes and spleen of horses, instead of NAN, N-

glycolylneuraminic acid is present. Both acidic sugars are called sialic acid.

Sialic acid is also present in glycoproteins. Many isoforms of some glycoproteins simply

differ in number of sialic acid units attached at the end of oligosaccharide chain. In both

glycoproteins and gangliosides, sialic acid contributes negative charge to the molecules at

physiological pH.

Johann Thudichum (1829-1901) who discovered sphingolipids was puzzled about their

biological role and apparently he called these substances after the enigmatic sphinx.

The major function of the glycosphingolipids in many membranes is structural. With the

carbohydrate portion imparting them a specific orientation, these are present

asymmetrically in membranes just like glycoproteins.

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Figure 11: Glycosphingolipids as determinants of blood groups

In the immunology paper, the Karl Landsteiner ABO blood group system is discussed.

We do know, however, that for blood transfusion, the RBCs have to be of the compatible

group. The „A‟ and „B‟ are surface antigens on erythrocytes.

These surface antigens are in fact carbohydrate component of glycosphingolipids. Thus,

the person with „A‟ type blood group has a different glycosphingolipid on its erythrocytes

as compared to the person with „B‟ type blood group.

These molecules are also part of cellular receptors. The ganglioside GM, is a receptor for

cholera toxin. It is also believed that glycosphingolipids are involved in intercellular

communication during growth and development.

Many metabolic disorder relates to catabolism of gangliosides and other

glycosphingolipids. An example is Tay-Sach‟s disease in which the concentration of

ganglioside GM2 becomes very high as a specific β-N-acetyl hexosaminidase which

removes N-acetylgalactosamine is deficient. Tay-Sach‟s disease is usually fatal by age 3

of the infant.

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Waxes

Figure 12

Waxes are sometimes called biological waxes to distinguish them from paraffin waxes.

These are esters where both alcohols and fatty acids are long chain compounds.

These long chains result in waxes being solid with melting points in the range of 60-100

°C. These, in general, are higher than fats.

These long chains of both acid and alcohol components also make waxes highly

hydrophobic to the extent that these are described as a water repellant. This property is

exploited in nature for various purposes.

Honeycomb provides bees complete shelter from the rain. The skin glands of vertebrates produce

waxes which helps the skin and hair to remain soft, lubricated and protected from water.

Birds similarly produce waxes from their preen glands to make their feathers water repellant. The

high priced down jackets filled with feathers of the birds like goose become protective wear

against cold, snow and rain!

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Waxes find large number of applications in the pharma, cosmetic and similar industries. Next

time when you see/buy a high quality lip balm, look at the ingredients. It is likely to contain bees

wax!

Sperm whale is not the only one which exploits waxes to adjust buoyancy. Dinoflagellates, krill

and other crustaceans and other fishes have low density waxes in their swim bladder or other

tissues to obtain desired buoyancy.

A large number of terrestrial arthropods have waxes on their cuticle surfaces to decrease loss of

water from their body surfaces.

In general, waxes in marine animals contain higher amounts of unsaturated fatty acids and

alcohols. However, waxes are quite diverse in their structure depending upon their function in the

organism/plants.

The insect waxes generally contain saturated alcohols and fatty acids with their chains consisting

of carbons in 12 to >20 range. The giant whitefly Aleurodicus dugesti has C-chains of upto 30

carbons in both components.

In general, waxes have primary alcohols. The lipids of cuticules of melanopline grasshoppers

contain waxes with secondary alcohols.

In plants, cutins and suberin are the lipid polymers present in the hydrophobic layers of cell walls.

Cuticle is the cutin based layer on the epidermis of aerial organs of the plants. This controls the

water loss and movement of gases and solutes. In addition, cuticles contain waxes of C24-C34

saturated fatty acids and alcohols.

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Figure 13

Lanolin present in lamb‟s wool, Carnauba wax obtained from a Brazilian palm tree and wax from

Spermaceti oil of whales are industrial products used in ointments, polishes and lotions.

Figure 14

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Sperm whale is a massive marine. About one-third of its weight is due to its head. About 90% of the

weight of its head in turn is due to a blubbery part called spermaceti organ.

Typically spermaceti contains upto 18000 kg of lipids consisting of triglycerides and waxes. Presence

of a large number of UFA ensures that this is liquid at 37 °C which is the normal body temperature of

resting whale.

These whales dive down in deep sea in search of squids on which they feed. At that level, water is

both colder and denser. Whales are able to wait quietly (without much swimming) for schools of

squids to pass by.

Whale‟s physiology results in rapid cooling of the oil to become solid (it actually starts to crystallize

even at 31 °C) during the dive. The buoyant density of whale now matches with the denser water

around it.

At one time, before sperm whales became endangered, the spermaceti “oil” with waxes in it was a

valuable lubricant. Relentless hunting for the waxy oil made them the endangered specie.

The dew drop nestling on the plant leaf is always considered a visual delight. The cutin is the waxy

material which makes it happen!

The role of glycolipids in biomembranes, signal transduction and photosynthesis is well established.

Glycolipids and waxes are interesting molecules and form part of the diversity of lipids as a class of

biological molecules.

Summary

Glycolipids with inositol as sugar

Glycosyl glycerides

Cerebrosides

Gangliosides

Waxes and their applications

Documents

Structure and Function of Biomolecules II Biochemistry ...epgp.inflibnet.ac.in/epgpdata/uploads/epgp_content/S000002BI/P000… · Phosphatidyl moiety, simple glycerol moiety and sphingosine