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bài giảng lipid (english)

fatty acid synthesis

Trans-fatty acids are manufactured fats created during a process called hydrogenation, which is aimed at stabilizing
polyunsaturated oils to prevent them from becoming rancid and to keep them solid at room temperature. They may
be particularly dangerous for the heart and may pose a risk for certain cancers. Hydrogenated fats are used in stick
margarine, fast foods, commercial baked goods (donuts, cookies, crackers), processed foods, and fried foods.

CHAPTER 1 - LIPID STRUCTURE
A: Lipid Structure
BIOCHEMISTRY - DR. JAKUBOWSKI
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 acylchains 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
Symbol

common name

systematic name

structure

mp(C)

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
Symbol

common name

systematic name

structure

mp(C)

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
acid

CH3(CH2)4(CH=CHCH2)2(CH2)6COOH

-9

18:3∆9,12,15

α−Linolenic acid

9,12,15
-Octadecatrienoic acid

CH3CH2(CH=CHCH2)3(CH2)6COOH

-17

20:4∆5,8,11,14

arachidonic acid

5,8,11,14Eicosatetraenoic acid

CH3(CH2)4(CH=CHCH2)4(CH2)2COOH

-49

20:5∆5,8,11,14,17

EPA

5,8,11,14,17Eicosapentaenoic- acid

CH3CH2(CH=CHCH2)5(CH2)2COOH

-54

22:6 ∆ 4,7,10,13,16,19

DHA

Docosohexaenoic acid

22:6ω3

% FATTY ACIDS IN VARIOUS FATS

FAT

<16:0

16:1

18:0

18:1

18:2

18:3

20:0

22:1

22:2

.

Coconut

87

.

3

7

2

.

.

.

.

.

Canola

3

.

11

13

10

.

7

50

2

Olive
Oil

11

.

4

71

11

1

.

.

.

.

Butterfat

50

4

12

26

4

1

2

.

.

.

The figure below shows the relative conformations of saturated and unsaturated fatty acids, and in comparison, the conformations and
potential energy graph for n-butane, which should provide insight into conformational changes in the nonpolar tail of fatty acids arising from
rotation around C-C single bonds. We will explore this diagram a bit latter.
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 betaoxidation 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


fed diets high in plant 18:2(n-6) fats accumulate 20:4(n-6) fatty acids in their tissues while those 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 CH3 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 CH3 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
Triacylglyceride/Phospholipid Stereochemistry

Glycerol is an achiral molecule, since C2 has two identical substituents, -CH2OH. Glycerol in the body can be chemically converted to
triacylglycerides and phospholipids (PL) which are chiral, and which exist in one enantiomeric form. How can this be possible if the two
CH2OH groups on glycerol are identical? It turns out that even though these groups are stereochemically equivalent, we can differentiate
them as follows. Orient glycerol with the OH on C2 pointing to the left. Then replace the OH of C1 with OD, where D is deuterium. Now the
two alcohol substituents on C1 and C3 are not identical and the resulting molecule is chiral. By rotating the molecule such that the H on C2
points to the back, and assigning priorities to the other substituents on C2 as follows: OH =1, DOCH2 =2, and CH2OH = 3, it can be seen
that the resulting molecule is in the S configuration. Hence we say that C1 is the proS carbon. Likewise, if we replaced the OH on C3 with
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
CH2OH 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 CH2OH 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 PO4 from ATP to the proR CH2OH of glycerol
on formation of chiral triacylglycerols and phosphatidic acid.


Lauric acid

IUPAC name

dodecanoic acid
Identifiers

CAS number

143-07-7

PubChem

3893

SMILES

CCCCCCCCCCCC(=O)O

Properties
Molecular formula

C12H24O2


Molar mass

200.31776

Density

0.880 g/cm³

Melting point
Boiling point

44-46 °C
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 (the
most 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 metabolismraising 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
Vapor density: 6.20
Vapor pressure: 1 mm at 121 C
Flash point: >113°C (>235°F)
Viscosity: 7.30 mPa-s at 323 K
Melting Point: 44°C

[edit] Stability
Stable. Combustible. Incompatible with bases, oxidizing agents, reducing agents. Although lauric acid will burn, it
tends to melt and vaporize unless it is in contact with an oxidizing agent or has been heated extremely quickly.

[edit] Toxicology


Eye, skin and respiratory irritant.

[edit] Transport information
Non-hazardous for air, sea and road transport. May cause burns.

Lipids: fatty acids
Butyric - Hexanoic - Caprylic - Decanoic - Lauric - Myristic - Palmitic - Stearic - Arachidic Saturated
Behenic
Omega-3 fatty acid Alpha-linolenic - Stearidonic acid - Eicosapentaenoic acid - Docosahexaenoic acid
Omega-6 fatty acid Linoleic - Gamma-Linolenic acid - Dihomo-gamma-linolenic acid - Arachidonic
Omega-9 fatty acid Oleic - Erucic

Stearic acid
IUPAC
name

stearic acid

Identifiers
CAS number

57-11-4

PubChem

5281

SMILES

CCCCCCCCCCCCCCCCCC(=O)O

Properties
Molecular formula

C18H36O2

Molar mass

284.47724

Density

0.847 g/cm3 at 70 °C

Melting point
Boiling point

69.6 °C
383 °C

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 CH 3(CH2)16COOH. Its name
comes 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.
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.
Esters

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] Reactions
Stearic acid undergoes the typical reactions of unsaturated carboxylic acids, notably reduction to stearyl alcohol, and
esterification with a range of alcohols.

[edit] Metabolism
An isotope labeling study in humans[1] concluded that the fraction of dietary stearic acid oxidatively desaturated to oleic acid
was 2.4 times higher than the fraction of palmitic acid analogously converted to palmitoleic acid. Also, stearic acid was less
likely to be incorporated into cholesterol esters. These findings may indicate that stearic acid is less unhealthy than
other saturated fatty acids.

[edit] See also


Magnesium stearate

1.

^

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



Merck Index, 11th Edition, 8761.


Palmitic acid
IUPAC name

palmitic acid
Identifiers

CAS number

57-10-3

PubChem

985

SMILES

CCCCCCCCCCCCCCCC(=O)O

Properties
Molecular formula

C16H32O2

Molar mass

256.42408

Density

0.853 g/cm3 at 62 °C

Melting point
Boiling point

63-64 °C
21 °C at 15 mmHg

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 of
place 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 (CH 3CHOH). 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".
Some while ago I gave a talk on the occasion of a group retreat seminar of the Polymer Spectroscopy Department
(Prof. Spiess), which was also intended as a general theoretical introduction to lipid bilayers (with special
emphasis on the Helfrich Hamiltonian). If you want, you can also have a look at my PowerPoint talk.
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, and
another 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 in
the 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 all
the 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 learn
about 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 scale
deformations 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 twodimensional!

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 3vector). Since a membrane is smooth, the function is smooth. Hence, a membrane is for instance
described by something which looks like r(u1,u2).
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.

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If we call the two curvatures c1 and c2, we can for instance form the two quadratic expressions c12 and
c22. However, for reasons which again are to be found in books on differential geometry, it is far more
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
Gaussian curvature. It can easily be seen that from the knowledge of H and K we can work out c 1 and c2
-- and vice versa. So it does not matter which set of curvatures we work with.
We're almost done. All we need to invent now is two constants of proportionality k 1 and k2, called elastic
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 total
energy due to curvature deformations is then given by a surface integral over the entire membrane, in
which 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 lipid
molecules 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 to
consider the bilayer as a thin sheet of highly viscous fluid with a viscosity similiar to olive oil surrounded by less
viscous 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 nonpolar tails hide from water molecules (Hydrophobic).

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 phospholipids
are 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 the
inside. 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 a
stroke. 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 hormoneinduced 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 cholesterol
are 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 releasing
the 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 the
passage of molecules into, and out of, the cell. You can compare the plasma membrane to a fence
around the cell. Actually, it is more like a chain-link fence, in that small molecules like water can sneak
through 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 of
functions, 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 of
factors 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


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