bài giảng lipid (english)

The rest of this unit on lipids will focus not on triacylglycerides, whose main function is energy storage, but on fatty acids and phospholipids, and the structures they form in aqueous

fatty acid synthesis

Saponifiable and Nonsaponifiable Lipids

Lipids can be considered to be biological molecules which are soluble in organic solvents, such as chloroform/methanol, and are sparingly soluble in aqueous solutions There are two major classes, saponifiable and nonsaponifiable, based on their reactivity with strong bases The nonsaponifiable classes include the "fat-soluble" vitamins (A, E) and cholesterol

Figure: Examples saponifiable and nonsaponifiable lipids

Saponification is the process that produces soaps from the reaction of lipids and a strong base The saponifiable lipids contain long chain carboxylic acids, or fatty acids, esterified to a “backbone” molecule, which is either glycerol or sphingosine

Note on nomenclature: Lipids are often distinguished from another commonly used word, fats Some define fats as lipids that contain fatty acid that are esterified to glycerol I will use the lipid and fat synonymously.

The major saponifiable lipids are triacylglycerides, glycerophospholipids, and the sphingolipids The first two use glycerol as the backbone Triacylglycerides have three fatty acids esterified to the three OHs on glycerol Glycerophospholipids have two fatty acids esterified at carbons 1 and 2, and a phospho-X groups esterifed at C3 Spingosine, the backbone for spingolipids, has a long alkyl group connected at C1 and a free amine at C2, as a backbone In spingolipids, a fatty acid is attached through an amide link at C2, and a H or esterified phospho-X group is found at C3 A general diagrams showing the difference in these structures is shown below

Figure: Classification of common phospholipids, glycolipids, and triacylglyerides

The actual chemical structures of these lipids are shown below.

Figure: Structures of common phospholipids

Figure: Comparison of lipids with glycerol and sphingosine as backbones

Properties of Lipids

The structure of these molecules determines their function For example, the very insoluble triacylglycerides are used as the predominant storage form of chemical energy in the body In contrast to polysaccharides such as glycogen (a polymer of glucose), the Cs in the acyl- chains of the triacylglyceride are in a highly reduced state The main source of energy to drive not only our bodies but also our society is that obtained through oxidizing carbon-based molecules to carbon dioxide and water, in a reaction which is highly exergonic and exothermic Sugars are already part way down the free energy spectrum since each carbon is partially oxidized 9 kcal/mol can be derived from the complete oxidation of fats, in contrast to 4.5 kcal/mol from that of proteins or carbohydrates In addition, glycogen is highly hydrated For every 1 g of glycogen, 2 grams of water is H-bonded to it Hence it would take 3 times more weight to store the equivalent amount of energy

in carbohydrates as is stored in triacylglyceride, which are stored in anhydrous lipid "drops" within cells The rest of this unit on lipids will focus not on triacylglycerides, whose main function is energy storage, but on fatty acids and phospholipids, and the structures they form in aqueous solution.

The structure of fatty acids and phospholipids show them to amphiphilic - i.e they have both hydrophobic and hydrophilic domains Fatty acids can be represented in "cartoon-form" as single chain amphiphiles with a circular polar head group and a single acyl non-polar tail extending from the head Likewise, phospholipids can be shown as double chain amphiphiles Even cholesterol can be represented this way, with its single OH group as the polar head, and the rigid 4 member rings as the hydrophobic “tail” Even through there are a very large number of fatty acids which can be esterified to C1 and C2 of phospholipids and a variety of P-X groups at C3, making the phospholipids and fatty acids extremely heterogeneous groups of molecules, their role in biological structures can be understood quite simply by modeling them either as single or double chain amphiphiles This reduces their apparent complexity dramatically In addition, they, in contrast to carbohydrates, amino acids, and nucleotides, do not form covalent polymers Hence we will start our studies of biological molecules with lipids (fatty acids and phospholipids) and then apply our understanding of this class of molecules to the more complex systems of biological polymers We will see that phospholipids and sphingolipids are essential components of membrane structure Cholesterol is also found in membranes and is a precursor of steroid hormones.

Fatty acid structure and conformation

Fatty acids can be saturated (contain no double bonds in the acyl chain), or unsaturated (with either one -monounsaturated - or multiple - polyunsaturated - double bond(s)) The table below gives the names, in a variety of formats, of common fatty acids

Table: Names and structures of the most common fatty acids COMMON BIOLOGICAL SATURATED FATTY ACIDS

12:0 Lauric acid dodecanoic acid CH3(CH2)10COOH 44.2

14:0 Myristic acid tetradecanoic acid CH3(CH2)12COOH 52

16:0 Palmitic acid Hexadecanoic acid CH3(CH2)14COOH 63.1

18:0 Stearic acid Octadecanoic acid CH3(CH2)16COOH 69.6

20:0 Arachidic aicd Eicosanoic acid CH3(CH2)18COOH 75.4

COMMON BIOLOGICAL UNSATURATED FATTY ACIDS

16:1 ∆9 Palmitoleic acid Hexadecenoic acid CH3(CH2)5CH=CH-(CH2)7COOH -0.5

18:1 ∆9 Oleic acid 9-Octadecenoic acid CH3(CH2)7CH=CH-(CH2)7COOH 13.4

18:2 ∆9,12 Linoleic acid 9,12 -Octadecadienoic

22:6 ∆ 4,7,10,13,16,19 DHA Docosohexaenoic acid 22:6 ω 3

% FATTY ACIDS IN VARIOUS FATS

Figure: Conformations of fatty acids and n-butane

Fatty acids can be named in many ways

 symbolic name: given as x:y (∆ a,b,c) where x is the number of C’s in the chain, y is the number of double bonds, and a, b, and c are the positions of the start of the double bonds counting from C1 - the carboxyl C Saturated fatty acids contain no C-C double bonds Monounsaturated fatty acids contain 1 C=C while polyunsaturated fatty acids contain more than 1 C=C Double bonds are usual cis

 systematic name using IUPAC nomenclature The systematic name gives the number of Cs (e.g hexadecanoic acid for 16:0) If

the fatty acid is unsaturated, the base name reflects the number of double bonds (e.g octadecenoic acid for 18:1 ∆ 9 and

octadecatrienoic acid for 18:3∆ 9,12,15 )

 common name: (e.g oleic acid, which is found in high concentration in olive oil)

You should know the common name, systematic name, and symbolic representations for these saturated fatty:

 lauric acid, dodecanoic acid, 12:0

 palmitic acid, hexadecanoic acid, 16:0

 stearic acid, octadecanic acid, 18:0

Learn the following unsaturated fatty acids -

 oleic acid, octadecenoic acid, 18:1 ∆ 9

 linoleic acid, octadecadienoic acid, 18:2 ∆ 9,12

 α-linolenic acid, octadecatrienoic acid, 18:3 ∆ 9,12,15 (n-3)

 arachidonic acid, eicosatetraenoic acid, 20:4 ∆ 5,8,11,14 (n-6)

 eicosapentenoic acid (EPA), 20:5 ∆ 5,8,11,14,17 (n-3) Note: sometimes written as eicosapentaenoic

 docosahexenoic acid (DHA) 22:6 ∆4,7,10,13,16,19 (n-3) Note: sometimes written as docosahexaenoic

There is an alternative to the symbolic representation of fatty acids, in which the Cs are numbered from the distal end (the n or ω end) of the

acyl chain (the opposite end from the carboxyl group) Hence 18:3 ∆ 9,12,15 could be written as 18:3 ( ω -3) or 18:3 (n -3) where the terminal C

is numbered one and the first double bond starts at C3 Arachidonic acid is an ( ω -6) fatty acid while docosahexaenoic acid is an ( ω -3) fatty acid.

Note that all naturally occurring double bonds are cis, with a methylene spacer between double bonds - i.e the double bonds are not conjugated For saturated fatty acids, the melting point increases with C chain length, owing to increased likelihood of van der Waals (London or induced dipole) interactions between the overlapping and packed chains Within chains of the same number of Cs, melting point decreases with increasing number of double bonds, owing to the kinking of the acyl chains, followed by decreased packing and reduced intermolecular forces (IMFs) Fatty acid composition differs in different organisms:

 animals have 5-7% of fatty acids with 20-22 carbons, while fish have 25-30%

 animals have <1% of their fatty acids with 5-6 double bonds, while plants have 5-6% and fish 15-30%

Many studies support the claim the diets high in fish that contain abundant n-3 fatty acids, in particular EPA and DHA, reduce inflammation and cardiovascular disease n-3 fatty acids are abundant in high oil fish (salmon, tuna, sardines), and lower in cod, flounder, snapper, shark, and tilapia

The most common polyunsaturated fats (PUFAs) in our diet are the n-3 and n-6 classes Most abundant in the n-6 class in plant food is linoleic acid (18:2n-6, or 18:2 ∆9,12 ), while linolenic acid (18:3n-3 or 18:3 ∆9,12,15 ) is the most abundant in the n-3 class These fatty acids are essential in that they are biological precursors for other PUFAs Specifically,

 linoleic acid (18:2n-6, or 18:2 ∆9,12 ) is a biosynthetic precursor of arachidonic acid (20:4n-6 or 20:4 ∆5,8,11,14 )

 linolenic acid (18:3n-3, or 18:3 ∆9,12,15 ) is a biosynthetic precursor of eicosapentaenoic acid (EPA, 20:5n-3 or

20:5 ∆5,8,11,14,17 ) and to a much smaller extent, docosahexaenoic acid (DHA, 22:6n-3 or 22:6 ∆4,7,10,13,16,19 )

These essential precursor fatty acids are substrates for intracelluar enzymes such as elongases, desaturases, and oxidation type enzymes in the endoplasmic reticulum and another organelle, the peroxisome (involved in oxidative metabolism of straight chain and branched fatty acids, peroxide metabolism, and cholesterol/bile salt synthesis) Animals

beta-fed diets high in plant 18:2(n-6) fats accumulate 20:4(n-6) fatty acids in their tissues while those beta-fed diets high in plant 18:3(n-3) accumulate 22:6(n-3 Animals fed diets high in fish oils accumulate 20:5 (EPA) and 22:6 (DHA) at the expense of 20:4(n-6)

Recent work has suggested that contrary to images of early hominids as hunters and scavengers of meat, human brain development might have required the consumption of fish which is highly enriched in arachidonic and docosahexaenoic acids A large percent of the brain consists of lipids, which are highly enriched in these two fatty acids These acids are necessary for the proper development of the human brain and in adults, deficiencies in these might contribute to cognitive disorders like ADHD, dementia, and dyslexia These fatty acids are essential in the diet, and probably could not have been derived in high enough amounts from the eating of brains of other animals The mechanism for the protective effects of n-3 fatty acids in health will be explored later in the course when we discuss prostaglandins synthesis and signal

transduction

Saturated fatty acids chains can exist in many conformations resulting from free rotation around the C-C bonds of the acyl chains A quick review of the conformations of n-butane shows that the energetically most favorable conformation is one in which the two CH 3 groups attached to the 2 methylene C’s (C2 and C3) are trans to each other, which results in decreased steric strain Looking at a Neuman

projection of n-butane shows the dihedral or torsional angle of this trans conformation to be 180 degrees When the dihedral angle is 0 degrees, the two terminal CH 3 groups are syn to each other, which is the conformation of highest energy When the angle is 60 (gauche+) or

300 (gauche-) degrees, a higher, local minimum is observed in the energy profile At a given temperature and moment, a population of molecules of butane would consist of some in the g+ and g- state, with most in the t state The same applies to fatty acids To increase the number of chains with g+tg- conformations, for example, the temperature of the system can be increased

Triacylglyeride/Glycerophospholipid Structure

A cartoon diagram showing the generic structures of triacylglyerides, glycerophospholipid and sphingolipids are show above In addition, the most common glycerophospholipids are shown Learn the structures of phosphatic acid (PI), phosphatidyethanolamine (PE),

phosphatidylcholine (PC) which is often called lechitin, and phosphatidylserine (PS) which is often called cephalin

If you are working at a PC in a public access area, you can use a internet browser plug-in (which is already installed in those areas) called Chime It will allow you to view and manipulate molecular models interactively on your computer Every time you see the helix icon, the link will take you to a Chime model for the molecule listed You should be able to see and rotate your molecule by placing the mouse cursor

in the black window and using the commands given below:

 Hold down the left mouse button and move the mouse around to rotate the molecule

 Hold down both the shift key and the left mouse button, then move the mouse up to zoom out or down to zoom in

 Hold down both the control button and the right mouse button, then move the mouse to translate the molecule on the xy axes

OD, we will form the R enantiomer Hence C3 is the proR carbon This shows that in reality we can differentiate between the two identical

CH 2 OH substituents We say that glycerol is not chiral, but prochiral (Think of this as glycerol has the potential to become chiral by

modifying one of two identical substituents.)

Glycerol - A prochiral molecule

We can relate the configuation of glycerol above, (when OH on C2 is pointing to the left) to the absolute configuration of L-glyceraldehyde,

a simple sugar (a polyhydroxyaldehyde or ketone), another 3C glycerol derivative This molecule is chiral with the OH on C2 (the only chiral carbon) pointing to the left It is easy to remember that any L sugar has the OH on the last chiral carbon pointing to the left The enantiomer (mirror image isomer) of L-glyceraldehyde is D-glyeraldehyde, in which the OH on C2 points to the right Biochemists use L and D for lipid, sugar, and amino acid stereochemistry, instead of the R,S nomenclature you used in organic chemistry The stereochemical designation of all the sugars, amino acids, and glycerolipids can be determined from the absolute configuration of L- and D-glyceraldehyde.

The first step in the in vivo (in the body) synthesis of chiral derivatives from the achiral glycerol involves the phosphorylation of the OH on

C3 by ATP (a phosphoanhydride similar in structure to acetic anhydride, an excellent acetylating agent) to produce the chiral molecule glycerol phosphate Based on the absolute configuration of L-glyceraldehyde, and using this to draw glycerol (with the OH on C2 pointing to

the left), we can see that the phosphorylated molecule can be named L-glycerol-3-phosphate However, by rotating this molecule 180 degrees, without changing the stereochemistry of the molecule, we don't change the molecule at all, but using the D/L nomenclature above,

we would name the rotated molecule as D-glycerol-1-phosphate We can’t give the same molecule two different names Hence biochemists

have developed the stereospecific numbering system (sn), which assigns the 1-position of a prochiral molecule to the group occupying the

proS position Using this nomenclature, we can see that the chiral molecule described above, glycerol-phosphate, can be unambiguously

named as sn-glycerol-3-phosphate The hydroxyl substituent on the proR carbon was phosphorylated.

Figure: The biological synthesis of triacylglycerides and phosphatidic acid from prochiral glycerol.

The enzymatic phosphorylation of prochiral glycerol on OH of the proR carbon to form sn-glycerol-3-phosphate is illustrated in the link below As we were able to differentiate the 2 identical CH 2 OH substitutents as containing either the proS or proR carbons, so can the enzyme The enzyme can differentiate identical substituents on a prochiral molecule if the prochiral molecule interacts with the enzyme at three points Another example of a prochiral reactants/enzyme system involves the oxidation of the prochiral molecule ethanol by the enzyme alcohol dehydrogenase, in which only the proR H of the 2 H’s on C2 is removed (We will discuss this later.)

Figure: How an enzyme (glycerol kinase) transfers a PO 4 from ATP to the proR CH 2 OH of glycerol

on formation of chiral triacylglycerols and phosphatidic acid.

Molar mass 200.31776

Density 0.880 g/cm³

Melting point 44-46 °C

Boiling point 225 °C at 100 mmHg

Except where noted otherwise, data are given for

materials in their standard state (at 25 °C, 100 kPa) Infobox disclaimer and references

Lauric acid, or dodecanoic acid, is a saturated fatty acid with the structural formula CH3(CH2)10COOH It is the main acid in coconut oil and in palm kernel oil, and is believed to have antimicrobial properties It is also found in human

milk(5.8% of total fat), cows milk(2.2%), and goat milk(4.5%) It is a white, powdery solid with a faint odor of bay oil or soap

[ edit ] Uses

Lauric acid, although slightly irritating to mucous membranes, has a very low toxicity and so is used in many soaps and shampoos Sodium lauryl sulfate is the most common lauric-acid derived compound used for this purpose Because lauric acid has a non-polar hydrocarbon tail and a polar carboxylic acid head, it can interact with polar solvents (themost important being water) as well as fats, allowing water to dissolve fats This accounts for the abilities of

shampoos to remove grease from hair Another use is to raise metabolism, believed to derive from lauric acid's activation of 20% of thyroidal hormones, otherwise which lay dormant.[citation needed] This is supposed from lauric acid's release of enzymes in the intestinal tract which activate the thyroid.[citation needed] This could account the metabolism-raising properties of coconut oil

Because lauric acid is inexpensive, has a long shelf-life, and is non-toxic and safe to handle, it is often used in laboratory investigations of melting-point depression Lauric acid is a solid at room temperature but melts easily in boiling water, so liquid lauric acid can be treated with various solutes and used to determine their molecular masses.Reduction of lauric acid yields 1-dodecanol

[ edit ] Physical data

Eye, skin and respiratory irritant.

[ edit ] Transport information

Non-hazardous for air, sea and road transport May cause burns

Lipids : fatty acids SaturatedButyric - Hexanoic - Caprylic - Decanoic - Lauric - Myristic - Palmitic - Stearic - Arachidic -

Behenic

Omega-3 fatty acidAlpha-linolenic - Stearidonic acid - Eicosapentaenoic acid - Docosahexaenoic acid

Omega-6 fatty acidLinoleic - Gamma-Linolenic acid - Dihomo-gamma-linolenic acid - Arachidonic

Omega-9 fatty acidOleic - Erucic

Except where noted otherwise, data are given for

materials in their standard state (at 25 °C, 100 kPa) Infobox disclaimer and references

Stearic acid (IUPAC systematic name: octadecanoic acid) is one of the useful types of saturated fatty acids that comes from

many animal and vegetable fats and oils It is a waxy solid, and its chemical formula is CH3(CH2)16COOH Its namecomes from the Greek word stéar (genitive: stéatos), which means tallow The term stearate is applied to the salts and

esters of stearic acid.

[ edit ] Production

Stearic acid is prepared by treating animal fat with water at a high pressure and temperature, leading to the

hydrolysis of triglycerides It can also be obtained from the hydrogenation of some unsaturated vegetable oils Common stearic acid is actually a mix of stearic acid and palmitic acid, although purified stearic acid is available separately

[ edit ] Uses

Stearic acid is useful as an ingredient in making candles, soaps, plastics, oil pastels and cosmetics, and for softening rubber Stearic acid is used to harden soaps, particularly those made with vegetable oil

Stearic acid is also used as a parting compound when making plaster castings from a plaster piece mold or waste

mold and when making the mold from a shellacked clay original In this use, powdered stearic acid is dissolved in

water and the solution is brushed onto the surface to be parted after casting

Esters of stearic acid with ethylene glycol, glycol stearate and glycol distearate are used to produce a pearly effect in shampoos, soaps, and other cosmetic products They are added to the product in molten form and allowed to crystalize under controlled conditions

In fireworks, stearic acid is often used to coat metal powders such as aluminium and iron This prevents oxidation allowing compositions to be stored for longer

It is used along with simple sugar or corn syrup as a hardener in candies

Also it is where the common scent of crayons is derived

[ edit ] See also

• Magnesium stearate

[ edit ] References

1 ^ Emken, Edward A (1994) "Metabolism of dietary stearic acid relative to other fatty acids in human subjects" (PDF) American Journal of Clinical Nutrition 60: 1023S–1028S Retrieved on 2006-08-07

Except where noted otherwise, data are given for

materials in their standard state (at 25 °C, 100 kPa) Infobox disclaimer and references

Palmitic acid, or hexadecanoic acid in IUPAC nomenclature, is one of the most common saturated fatty acids found in animals and plants As its name indicates, it is a major component of the oil from palm trees (palm oil and palm kernel oil) The word palmitic is from the French "palmitique", the pith of the palm tree Butter, cheese, milk and meat also contain this fatty acid [citation needed]

Palmitate is a term for the salts or esters of palmitic acid The palmitate anion is the observed form of palmitic acid

at physiological pH [citation needed]

[ edit ] Biochemistry

Palmitic acid is the first fatty acid produced during lipogenesis (fatty acid synthesis) and from which longer fatty acids can be produced Palmitate negatively feeds back on acetyl-CoA carboxylase (ACC) which is responsible for converting acetyl-ACP to malonyl-ACP on the growing acyl chain, thus preventing further palmitate generation [citation needed]Reduction of palmitic acid yields cetyl alcohol [citation needed]

[ edit ] Uses

Palmitate is an antioxidant and a vitamin A compound added to low fat milk to replace the vitamin content lost through the removal of milk fat Palmitate is attached to the alcohol form of vitamin A, retinol, in order to make vitamin A stable in milk [citation needed]

Derivatives of palmitic acid were used in combination with naphtha during World War II to produce napalm (naphthenic

and palmitic acids) [citation needed]

The WHO reports "convincing" evidence that dietary intake of palmitic acid increases risk of developing

cardiovascular diseases [1] However, possibly less-disinterested studies have shown no ill effect, or even a favorable effect, of dietary consumption of palmitic acid on blood lipids and cardiovascular disease, so that the WHO finding may be deemed controversial.[2] The controversy may be resolved by a study showing palmitic acid to have no hypercholesterolaemic effect if intake of linoleic acid was greater than 4.5% of energy, but that if the diet contained trans fatty acids, the health effects would be unfavorable (with an LDL cholesterol increase and HDL cholesterol decrease) [3]

How does alcohol affect the structure of a cell membrane?

Alcohol disrupts the normal organization of the lipid carbon chains (see picture below.)

Your scientist/author of this module believes that alcohol sticks to a membrane near its surface with water Some of the evidence that supports this idea was obtained with a simple artificial lipid

membrane Several methods demonstrate that alcohol binds just underneath the charged head group of surface lipid, displacing some of the water that is normally there The importance of this physical disruption is not so much what it does to the lipid, but what it does to the proteins (not shown) that are embedded in the lipid Disturbing the shape of the lipids changes the shape of the proteins, and thus changes the functions of the protein.

This drawing uses lollipop symbols for the phospholipids(the lipid portion of cell membranes.) The presence of alcohol (the black blob) shifts the lipid molecules out ofplace and breaks up their orderly arrangement This makes the membrane more liquid like (Like

changing cold butter to a more liquid form like warm margarine.)

Why does shifting the lipids cause problems?

Think about how the substitution of alcohol for water might affect the large, complex sugars and proteins that are embedded in the lipid membrane Ask yourself:

1 Wouldn't the substitution cause proteins to change shape?

2 If they changed shape, could that cause them to change function?

Although the lipid of a membrane has no special function of its own, it does influence the large functional molecules (proteins and sugars) that the membrane contains This is not a good thing Changing a protein's shape or location can change the protein's function Some membrane proteins are affected more by alcohol than are other proteins

For a learning activity about alcohol intoxication, see Activity #4

A Toxic Substance -Alcohol

Why is alcohol a toxic, or hazardous, substance?

Alcohol is attracted to cell membranes, and it concentrates there When it reaches nerve cell

membranes, the alcohol can change the function of nerve cells and thus affect behavior This change in behavior is commonly called intoxication.

How does alcohol affect cell membranes?

At one time, scientists believed that alcohol "dissolved" into the membrane interior and made the carbon chains of the lipids more fluid (It was thought to be like converting hard butter into soft

margarine.)

When scientists tested this idea on fish, they realized that the "melted butter" idea could not explain intoxication Warming fish by a few degrees can cause the same degree of lipid "melting", but the fish

do NOT get intoxicated.

So what causes intoxication?

The answer can be answered in part from the chemistry of alcohol (CH3CHOH) The carbon part of the molecule makes it attracted to the carbon tails of the lipids in cell membranes But the OH group of alcohol makes it attracted to water

Thus, you might expect that these influences would cause alcohol to orient itself in a membrane so that the carbon part of the molecule inserts itself into the membrane interior (where the lipid carbon tails are) and the OH part of the molecule is out near the surface, where the water is This idea has been recently confirmed by the author of Cells Are Us and his colleagues here at Texas A&M

The Lipid Bilayer

The following brief notes are intended as an overview of some basic concepts in the field of fluid

membranes It may provide a better understanding of the ongoing research projects and is sorted in the form of a little "FAQ" It is intended for the laymen; most "facts" explained here would need to be put more carefully to account for all the "except if", "provided that", and "however"

(Prof Spiess), which was also intended as a general theoretical introduction to lipid bilayers (with special

What are membranes?

The term "membrane" is often used in science and everyday life, and it means slightly different things in different contexts Very generally, a membrane is a two-dimensional "sheet" which can separate two space regions "Sheet" implies that a membrane is much thinner than it is long or wide, and this makes the term "two-dimensional" understandable Membranes usually possess some degree of flexibility (a plywood board would hardly be considered a membrane), and they are often permeable for certain substances – either because they have holes (like a sieve), or because their microscopic structure permits (active or passive) transport of "stuff" from one side to the other

More specifically, in the context of biology a membrane is a thin film, skin or layer of tissue covering a part of an animal or plant, or separating different layers of tissue; even more specifically, for a cell

biologist a membrane is the bilayer composed of phospholipids and embedded proteins which surrounds

each cell and which also occurs inside a cell in the form of many other organelles, for instance the Golgi

or the endoplasmic reticulum

What are fluid membranes?

Let us start with a "trivial" observation: A piece of paper can easily be bent, but it cannot be sheared

This means that one cannot lay down a piece of paper on a desk, put both hands flat on the paper and then move them relative to each other Yet in other words, even though a piece of paper is very flexible

with respect to out-of-plane motions, it is impossible to make in plane motions: Two dots painted on a

piece of paper will always have the same in-plane-distance, one cannot bring them closer or further apart In fact, this is why it makes sens to store information on paper

Membranes which have this property, (strong) in-plane shear resistance, are called tethered membranes.

They are basically two-dimensional solids which can be bent in the third dimension without breaking But

there is another class of membranes, namely, ones which are two-dimensional liquids These

membranes do not posses an in-plane shear resistance Two points marked on these membranes can

be moved within the membrane surface relative to each other Writing would be a futile attempt on these things! The example the reader will most likely be best familiar with is a soap film It is a membrane, but the film itself is a two-dimensional fluid

The kind of membranes we are interested in our research are fluid

What is a soap film?

Fluids don't come in sheets, they come in drops It is not straightforward to imagine, what one would have to do in order to come up with something which is a two-dimensional fluid! A droplet of water for instance is spherical, because the surface tension forces the droplet to assume the shape of least

surface at given volume If we somehow pull the droplet flat, it will spontaneously reform the droplet shape

One can reduce the surface tension by adding surfactant molecules to the water These molecules are in

some sense "schizophrenic", because they have one region which likes to surround itself with water, andanother region which dislikes this (it would rather like to surround itself with air or oil) These molecules readily accumulate between the air-water or oil-water interface and orient such that both their sides are inthe appropriate environment As a consequence, the surface tension is strongly reduced

A soap film is basically a thin water layer which is decorated on its two sides by surfactant molecules such that their hydrophobic (= water "fearing") sides stick into the surrounding air If their density at any point of the film is reduced, the surface tension there becomes larger and pulls back surfactant

molecules into this region This is why such films are stable

What is a lipid bilayer?

Lipids are basically a special kind of surfactant They are esters of fatty acids or related compounds and, just like surfactants, also consist of a hydrophilic (=water loving) "head" and a hydrophobic (double) "tail"

A biologically important example are phospholipids, for instance DOPC (Dioleoyl phosphatidylcholine),

DOPS (dioleoyl phosphatidylserine), or DOPE (dioleoyl phosphatidylethanolamine) For the time being

we are not so much concerned about the specific chemical structure (even though this is important also for the generic aspects of the lipids), but rather about the fact that these molecules can form double layers in an aqueous environment, in which two sheets (monolayers) of lipid molecules meet such that allthe hydrophobic sides are hidden from the water

The result of this aggregation of lipid molecules is a stable two-dimensional sheet in which the single molecules can move freely within the plane of the bilayer Thus, we have arrived at a fluid membrane! In fact, this kind of membrane is the key structural component of all living cells

How can we mathematically describe a membrane?

The mathematical description of membranes depends very crucially on what precisely one wants to learnabout them For instance, if one is interested in lipid-lipid interactions, their conformational order, their diffusion dynamics etc., one better uses a model which with an appropriate level of detail bothers about properties of these lipids If, on the other hand, general elastic properties of the membrane are under scrutiny, this may not be necessary at all

Currently my interest about membranes focuses on the elastic energy which come along with large scaledeformations of the membrane For this it is often not necessary to know, what precisely the membrane

is made of; it rather suffices to understand that it is a very thin elastic medium Correspondingly, the membrane may be described by a (smooth) surface embedded in space, and indeed now it is truly two-dimensional!

What we now essentially need to know is a function which describes the position of every point of the membrane in space Since the membrane has two dimensions, the function depends on two variables Since the membrane lives in three surrounding dimensions, the function has three components (it is a 3-vector) Since a membrane is smooth, the function is smooth Hence, a membrane is for instance

We don't need to go in any details here It suffices to say that very naturally we're led into the beautiful branch of mathematics which is called (classical) differential geometry, and which was founded by people like Meusnier, Monge, Gauss, Euler, Codazzi, and many others

What is the elastic energy of a membrane?

If we want to understand deformations of a membrane, we need to know how much energy this costs We're now naturally lead into the field of elasticity theory however, with a small twist: Usually, by

"elastic deformation" we mean the energy associated with somehow stretching a piece of material, i.e., changing distances between neighboring points In harmonic approximation ("linear elasticity"), the resulting energy cost is quadratic in the stretching energy (the local "gradient"), such that the force distance relation is linear ("Hooke's law")

This is a bit more tricky in the case of fluid membranes, which we want to think of as incompressible, two-dimensional liquids By incompressible we mean that we cannot increase the total area by pulling on

it from the sides However, we can still bend it, and this does not increase area But then, we are not really talking about local stretching, but local bending, which costs energy And in fact, what we need is

an expression which writes down the free energy as a function of the curvature of the membrane surface,and we would like it to be quadratic in this curvature

A curvy piece of wire has at every point a local curvature, which is the (inverse of the) radius of a circle which smoothly touches the wire at this point ("osculating circle") Membranes are two-dimensional, though Therefore a membrane has at every point two curvatures which describe its curvature properties.They are called principal curvatures, and their directions along the surface are called principal directions

It is not entirely trivial (but certainly not difficult either) to see that knowledge of these curvatures is

enough; but then, this is what differential geometry is good for

<>

clever not to use the principal curvatures themselves but rather the following expressions in all what

follows:

H := (c1+c2)/2 and K := c1 c2

The first expression, H, is called the mean curvature, and the second expression, K, is called the

and vice versa So it does not matter which set of curvatures we work with

moduli, which quantify how expensive a mean curvature or Gaussian curvature deformation is.Therefore, we can write the energy per unit area of a curved surface, in harmonic approximation, as:

e := 1/2 k1 H2 + k2 K

This expression goes back to Helfrich and is therefore often called the "Helfrich Hamiltonian" The totalenergy due to curvature deformations is then given by a surface integral over the entire membrane, inwhich one integrates up the above deformation energy density Very simple, in principle In practice

unfortunately very hard in all but a few "nice" situations

Protein Motion in Lipid Supervisors Dr Harlen & Dr LiverpoolBilayers

Cell membranes form the boundaries of a cell and also separate different parts of the cell interior The membranes

are formed from two layers of lipid molecules The lipid molecules are polar in that they have hydrophilic heads

pointing out of the membrane and hydrophobic tails portion forming the core In addition to the small lipidmolecules there are larger protein molecules embedded in the bilayer that act as gateways across the membrane.These transmembrane proteins are not fixed but are free to “float” around within the bilayer

This project will investigate flow within the bilayers and the motion of the protein molecules A simple model is toconsider the bilayer as a thin sheet of highly viscous fluid with a viscosity similiar to olive oil surrounded by lessviscous water

Phospholipids serve an extremely important function in our bodies, they form the cell membrane Think

of each cell as being surrounded by a fence, a fluid fence, but a fence none the less It is called the the cell membrane or the plasma membrane The cell membrane is composed of two layers, each composed

of trillions of Phospholipid molecules oriented in a special manner

Phospholipids are very much like triglycerides but with one important difference A phosphate functional group is substituted for one of the three fatty acids

The image on the left shows three different ways to depict Phospholipids The glycerol portion of the

molecule is shown in red in the Fisher drawing (atoms represented by letters) The two fatty acids are below the red and the phosphate group (with some methyl and amino decorations) is above You may also notice that j one of the fatty acids is saturated and the other, unsaturated

The most important feature of phospholipid structure is that the fatty acid "tails" are non-polar while

the phosphate "head" is very polar This leads to a chemically confused (solubilty-challenged) molecule When exposed to an aqueous (water) environment, phospholipids form unique assemblies called

"bilayers" The polar heads of the P-lipids turn toward the water molecules (Hydrophilic) while the polar tails hide from water molecules (Hydrophobic)

non-The structure that surrounds each of your cells (the plasma or cell membrane) is formed from a

Phospholipid bilayer The polar heads of the phospholipids are all facing the aqueous environments of

the outside, and the inside of the cell, while the non-polar tails form a fatty layer on the inside This

structure is an important barrier and defines the boundaries of living and unliving portions of a cell

The two-celled human embryo in this image looks like two bubbles stuck together The Phospholipid bilayer (membrane) is flexible, much like like a bubble, continually moving and flowing The phospholipidsare held together by only by weak hydrogen bonds of the heads and the even weaker interactions

between the hydrophobic lipid molecules in the tails

We have seen that Phospholipids form an unique structure when exposed to water The polar heads all turn outward to form H-bonds with the water molecules, while the hydrophobic lipid tails are hidden in theinside This Phospholipid bilayer structure forms the membrane that surrounds each of your cells and plays an important role in regulating cellular function

Cholesterol is just another lipid found in the plasma membrane It is an important part of a healthy body since cholesterol is used as part of the cell membranes, and also as part of some hormones But a high level of cholesterol in the blood - hypercholesterolemia- is a major risk factor for coronary heart disease, which can lead to heart attacks

Cholesterol and other fats can’t dissolve in the blood (since they are Hydrophobic) They have to be

transported to and from the cells by special lipid carriers called lipoproteins There are several kinds, but the ones to be most concerned about are low density lipoprotein (LDL) and high density lipoprotein (HDL)

Low density lipoprotein is the major cholesterol carrier in the blood When a person has too much LDL

cholesterol circulating in the blood, it can slowly build up within the walls of the arteries feeding the heart and brain Together with other substances it can form plaque, a thick, hard deposit that can clog those arteries This condition is known as arteriosclerosis

Trans Fatty Foods

Nutritional labels are not currently listing a possibly dangerous fat in the foods we eat The culprit is called trans fat, which is structurally different from saturated fat or cholesterol

Also called stealth or phantom fat, is created during the process called partial hydrogenation, which involves turning liquid vegetable oils to solid shortening Partially hydrogenated oils are used to make a wide variety of foods on supermarket shelves including some cookies and snacks

Although some of these foods claim to be low in calories or fat or cholesterol, the numbers are not listed for trans fat, which could be as bad or worse Research indicates that in some cases trans fat raises blood cholesterol and increases the risk of heart disease Both saturated fat and trans fat raise the

amount of LDL or bad cholesterol, but trans fat also lowers the amount of HDL or good cholesterol

The formation of a clot (or thrombus) in the region of this plaque can block the flow of blood to part of the heart muscle and cause a heart attack If a clot blocks the flow of blood to part of the brain, the result is astroke A high level of LDL cholesterol reflects an increased risk of arteriosclerosis and heart disease That is why LDL cholesterol is often called "bad" cholesterol

About one-third to one-fourth of blood cholesterol is carried by high density lipoprotein or HDL Medical

experts think HDL tends to carry cholesterol away from the arteries and back to the liver, where it’s passed from the body

Some experts believe HDL removes excess cholesterol from arteriosclerosis plaques and thus slows their growth HDL is known as "good" cholesterol because a high level of HDL seems to protect against heart attack The opposite is also true: a low HDL level indicates a greater risk

Lipid Hormones - Testosterone is responsible for sexual maturation at all stages of male development

throughout life Women also secrete small amounts of testosterone from their ovaries Synthetically, testosterone is prepared from cholesterol, the molecules are fairly similar Anabolic steroids, derivatives

of testosterone, have been used illicitly and are now controlled substances Testosterone is also

schedule C-III controlled substance

Hydrocortisone is a steroid hormone secreted by the adrenal cortex The anti-inflammatory effects of Hydrocortisone are believed to be due to modification of enzyme action rather than to a direct hormone-induced action Hydrocortisone has no anabolic effects

More membrane stuff, as we said: Phospholipids and cholesterol form the Plasma membrane

(membrane around each cell) The same type of membrane structures formed by phospholipids and cholesterolare found inside the cell as well as around it The nucleus, mitochondria and endomembrane system all are surrounded by their own phospholipid-bilayers

The membranes around these internal structures compartmentalize the biochemical reactions that occur

in each organelle" The Nucleus contains DNA The mitochondria perform catabolic reactions releasingthe Energy from sugars The endomembrane system synthesizes proteins, manufactures lipids, and

transports them to various places within the cell

Proteins are embedded in the Phospholipid-bilayer of the plasma membrane These proteins regulate thepassage of molecules into, and out of, the cell You can compare the plasma membrane to a fencearound the cell Actually, it is more like a chain-link fence, in that small molecules like water can sneakthrough the fence Larger molecules, however, have to enter through gates in the fence, protein gates

Like gates in a fence, these proteins control what goes in and out of the cell Glucose uptake, salt and Ion balance, amino acids, and nucleotides,every large molecule that enters or exits the cell, has to pass through these protein gates

Cells also have membrane proteins that attach the various cells together, identify each cell, and receive signals from other cells (e.g hormones)

The plasma membrane and its associated proteins are one of the most important elements of cell

structure and Biology The proteins found in the plasma membrane regulate growth and development, the immune system, nerve impulses, and play a major part when cells become Cancerous

Lipid droplet biology

Mathias Beller

Lipid droplets are the lipid storage organelles of all organisms Their important role in cellular and

organismic energy storage becomes most prominent in cases where lipid droplet biology is misregulated.This is for example the case in several major lipid storage diseases such as atherosclerosis, diabetes or obesity For a long time it was thought that lipid droplets only act as storage depots More recent data, however, support the idea that lipid droplets are highly dynamic organelles which participate in several cellular processes and interact with various other cellular compartments Despite their multifariousness offunctions, all lipid droplets share a simple, stereotyped structure of a hydrophobic core built of the

storage lipids (mainly triacylglycerols), surrounded by a phospholipid monolayer to which numerous proteins are attached (Fig 1) Although the central role of lipid droplets for energy storage was

demonstrated, little is known about their cellular biology such as biogenesis, mechanism of protein

association or size and number control inside cells

Recent work together with the group of Ronald Kühnlein demonstrated the evolutionary conservation offactors regulating lipid storage and led to the identification of a large number of proteins associated with

the lipid droplets of the Drosophila larval fat body Initial localization studies suggest the existence of lipid

droplet subpopulations Differences in the protein composition (Fig 2) might correlate with a change inmaturation status or metabolic activity, potentially reflecting the diverse functional repertoire of theseorganelles.

We use both tissue culture and in vivo techniques to test this hypothesis and characterize factors and

pathways necessary for lipid droplet function The combination of the proteomics data with the outcome

of additional high-throughput screening approaches (including RNAi-mediated functional genomics orgene expression profiling) generated a rich toolbox of factors which is utilized to unravel details of thelipid droplets biology

Adipose tissue

• Specialized sites occur in tissues for lipid storage

• Most cells have similar metabolic pathways for synthesis of fat

• There are two types of fat

a)White –commonly present and also in very primitive animals

b)Brown – rare in occurrence present in mitochondria and generates heat

• Adipose tissue is 70-905 triglyceride and cholestrol is 100-200 mg/100g

• About 70% of adipose is subcutaneous or inter- muscular

• Adipose may have an insulation function but this related to blood flow, not lipid r value

• Adipose tissue can withstand hypoxia

• It is organized into lobules or clusters of cells surrounded by connective tissue and is analogus

to perimysium

• Amount of connective tissue around a lobule depends on location If deeper then the fat has less matrix i.e subcutaneous fat has more structure than kidney fat

• The fat depot distinctions may be unclear

Functions of adipose tissue

• It supplies energy

• Insulation

• Provides minor physical protection

• Cholestrol storage and the percentage of the same changes with age

• Estrogen production from androstenedion

Composition of adipose tissue

The 90% of adipose tissue is tryglycerides Triglycerides consist of one molecule of glycerol and three molecules of fatty acids The composition of tryglycerides for different fatty acids differs in various

species wise for

percent)

Cattle ( in percent )

i) Palmiticii) Steariciii) Oleic

2715

40

2825

41

Fatty acid composition of different animal fats (in percentage)

ButyricCaproicCaprylicCapric

3.01.01.53.0