Aris Kaksis. Riga Stradin’s University 2014 http://aris.gusc.lv/06Daugavpils/Engl/LipdBiLayerMembran.doc
Lipid Phosphat-PO4--idyl Choline+Bilayer Membrane MW=760.10 g/mol
Phospho Lipids 1/3 mass fraction of Membranes to make 33.3% mass fraction 1/3 of total mass
Fatty Acid C16 palmitate nonpolar HydroCarbon
C15 tail between each methylene groups >CH2:2HC<
with two Hydrogen atoms Bonding Energy of London
Forces (Wan der Walls) for single contact point
Hydrogen atoms H::H is -2kJ/mol. For two contacts
between methylene groups are -4 kJ/mol = -2kJ/mol *2.
One interaction Force Energy are week as single one
interaction London Forces (Wan der Walls). Research
of molecules shows large number of contact points for
Lipid Bilayer Membrane Phospholipids like as
Phosphatidyl Choline.
Palmitate C16 saturated (no double Bonds) Fatty Acid chain has 30contact points (15*2) times -2 kJ/mol
accumulates the Bonding Energy -60 kJ/mol.
H
H
16
H
H
14
15
H
H
H
13
H
H
H
H
12
H
H
H
6
7
9
H
H
8
10
11
H
H
H
H
H
H
H
5
H
H
4
H
O
H
2
3
H
H
C
1
O
H
H
H
H
17
H
H
18
H
H
15
H
H
H
16
H
13
H
H
H
H
14
H
11
H
5
H
12
10
H
7
H
9
8
H
H
H
H
H
H
H
H
H
6
H
3
H
1
H
H
4
2
O
C
O
H
Oleate C18:1 unsaturated (with double Bond between C atoms like >C=C<) Fatty Acid Phospholipid
H
H
H
H
O
H
H
H
H
H
H
H
H
H
H
H
C
O
H
H
H
H
H
H
H
H
H
H
H
H
H H
H H
H H
H
H
H
H H
H
H
H
H
H
H
H
H
H
O
H
C
H
H
H
H
H
H
H
H
H
H
H
H
H
H
O
2) of two Palmitate C16 and Oleate C18:1 Fatty Acids methylene 15 contacts -2*2*15=-60 kJ/mol. For example two C16
3) Each Phospholipid Fatty Acid hydrocarbon chain
surrounded three closest
neighbor chains as gray
, yellow
and green
so total interaction Energy
for Phosphatidyl Choline is 3*-60 kJ/mol = -180 kJ/mol per one molecule with Fatty
Acids hydrocarbon chains C16 and C18:1 into mono Layer Membrane part.
4) Non polar Fatty Acid tails with two methyl groups –CH3 are in close contacts
between two mono Layers of Bilayer Membrane. Three hydrogen atoms of methyl group
touch to neighbor mono Layer methyl groups hydrogen atoms make hydrophobic
intermolecular forces of nonpolar medium hydrocarbon chains medium forming Fatty Acids C16 and C18:1.
1
H
H
H
C
H
CH
H
Water tetramer structure (H2O)4 press
together both mono Layers with
Hydrophobic forces -10 kJ/mol per each
contact point and six contact points Energy
-60 kJ/mol. Total interaction energy is
-240 kJ/mol: interaction London Forces
(Wan der Walls) -180 kJ/mol
plus -60 kJ/mol.
One side membrane fragment mono Layer twice has
London Forces (Wan der Walls) interactions Bonding
Energy -18 000*2 kJ/mol and single Hydrophobic
forces Bonding Energy -6000 kJ/mol between Bilayer
100+100 Phospho lipid Fatty Acid tails with methyl
groups –CH3 in BiLayer middle of waterless ↓
nonpolar medium of hydrocarbon medium ↓ formed
<=
from Fatty Acids carbon C16 chains ↓ and
carbon C18:1 chains (-36000+-6000=42000 kJ/mol).
Per each Lecithin molecule in BiLayer -42kJ/mol.
Bilayer Lipid Membrane waterless interior is
impermeable so work as isolating cell wall for
compartment components water molecules and water
solution: as salts and water soluble organic molecules.
Like as wall of buildings and of houses. Therefore
for entrance in the house we should use the doors, but
Membranes are equipped by transport enzymes
(proteins): Aquaporins for (H2O,O2,CO,NO,C3H8O3),
Proton channels for H+, Bicarbonate channels for
Given Phosphatidyl Choline Bilayer Membrane
HCO3-, Sodium Na+, Potassium K+, Magnesium Mg2+,
composition of 200 molecules surrounded by water
2+
molecules both side. Water molecules as polar molecules Calcium Ca , Chloride Cl , Glc – Gal – Man
interact with positively charged Choline nitrogen N+ and C6H12O6, 20 proteinogenic Amino Acids and so as for
other solutes in biological water solutions.
negatively charged Phosphate group PO4-.
Distance measurement of Phosphatidyl Choline Bilayer Membrane thickness has value l = 55.225 Å or 552 nm.
That means Cell Membrane and Cell organelle Membrane Layers has the thickness 55.2 Å or 552 nm.
1. Cell and organelle Membranes 1/3 mass part are composite of the Phospholipids like Phosphatidyl Choline.
2. Second third 1/3 part of Membranes mass constitutes 27 carbon Lipid Cholesterol molecules:
A
22
H HH
20
21
23
Cholesterol H HH
18
H HH
24
19
26
17
12
16
25
H HH 11 13
D
C 14
15
27
H HH
9
1
8
10
2
A5 B7
3
6
4
both angular methyl groups
H HH
19
H HH
18
H
H
H
H
H
H
H HH
HO
The four rings of the steroid are labeled A, B, C and D. The methyl
groups labeled 18 and 19 are like angular methyl groups –CH3 and
HO
double bond between carbon atoms 5 and 6 and alcohol at carbon 3.
Cholesterol make Membranes less fluid and flexible prevent its broking and following leaking of water
molecules and of water solution components: salts and water soluble organic molecules.
Membrane mass1/3 part constitute Phospholipids, second 1/3 part Cholesterols, third part of 1/3 mass are
3. Membranes integral Proteins 1/3 mass fraction of Membranes to make 33.3% of total mass: with
O-glycoside bonds Immunological determinants like as blood groups A, B, AB, 0 located outside in extra
cellular space for leucocytes scanners host bodies recognition, therefore Immunoglobulin name Antibody for
non host bodies recognition and binding to remove from Host body.
1.Cell Structural building blocks cytoskeleton and integral membrane proteins;
2.Transport enzymes (channels) integral membrane proteins,
3. Receptors enzymes (Membranes integral Proteins) of the Signal transduction Pathway components for
biological communication inside the cells, between the cells and or tissues, as well between living organisms.
2
G l y c e r o l s LIPIDS
Table I.2
Classification of Lipids
Lipid
Function
Fatty acids
Metabolic fuel; component of several other classes of lipids
Triglycerides
Main storage form of Fatty acids and chemical energy
Phospholipids
Component of membranes; source of Arachidonic acid for Eicosanoids production;
inositol triphosphate and diglyceride membrane inner location for signal transduction
Sphingolipids
Component of membranes molecule linkage location site in extracellular space
Cholesterol
Component 1/3 fraction of membranes; precursor of bile salts and steroid hormones
Bile salts
Lipid digestion and absorption; main product of cholesterol metabolism
Steroid hormones Intercellular signaling molecules, that regulate gene expression in target cells
Eicosanoids
Regulation of physiological functions:prostaglandins, tromboxans, leucotrienes, prostocyclin
Vitamins KEDA Vision A; calcium metabolism D; antioxidants E; blood coagulation K1;
Bone Phospho Apatites Ca3P3O10OH Calcium ions in correct Structure K2
Ketone bodies
Metabolic fuel
Table I.3 Carbon
Common
IUPAC Systematic name
A Some
atoms Structural Formulas.
Name
natural fatty
Fatty Acids break down in mitochondria through beta carbon
Notional
acids.
name
O2 oxidation reaction producing CO2, H2O and life energy
C
Saturated fatty acids
palm oil
palmitic acid
16C
CH3(CH2)14 CO2H hexadecanoic acid
Greek stear fat 18C
Arachis
20C
Peanut
CH3(CH2)16 CO2H
octadecanoic acid
20
18
16 14 12
6
8
1
10
4
H H
17
9
7
5
15 13 11
2
H
C

19 eicosanoic acid
 


OH
C
O
mp(°C)
63
stearic acid
70
arachidic acid
77
palmitoleic acid
-1
Unsaturated fatty acids
C16:1 w-7
Palm oil
9
6
1
4
16 15 14 1312 11 10 9 8 7
5
2
H H
C
H
  
cis- -hexadecenoic acid


C
OH
O
18
6
1
Latin
4
C18:2 w-6
H H17 16 15 14 13 12 11 10 9 8 7
OH
5
2
linoleic acid
-5
9, 12 H
oleum oil linseed
C
 C


cis- -octadecadienoic acid
O


oil
6
Latin
8
1
4
18 17 1615 14 13 12 11 10 9
-11
O H α-linolenic acid
7
5
2
H
H
linum flax,
C
C

 
9, 12, 15 H
O

and oleum C18:3 w-3
-octadecatrienoic acid

cis-
oil
TABLE I.4.
Essential
Fatty
Acid Nomenclature
Five blood plasma
Abbrev ia tion
System
transport
Descriptive Name
Numeric
D
n
C:=
w
forms
Palmitate
16:0
of Lipids
Palmitoleate
9—16:1
16:01 D 9
16:1n-7 16:01 w-7
Linoleate
9,12—18:2
18:02 D 9,12
18:2n-6 18:02 w-6
in Lipoprotein
Linolenate
9,12,15—18:3 18:03 D 9,12,15
18:3n-3 18:03 w-3
vesicles
Albumin
Fatty acid
and Water
insoluble
drug
transport
80200 nm
chylomicrons
2870 nm
very low
density
lipoproteins
2025 nm
low density
lipoproteins
3
812 nm
high density
lipoproteins
Apolipoproteins B-48, C-III, C-II
figure 17-2
Molecular
structure
of a chylomicron.
The surface is
a layer
of phospholipids,
with head groups
facing the aqueous
phase.
Triacylglycerols
sequestered in the
interior (yellow)
make up more
than 80% of the
mass. Several
apolipoproteins
that protrude from
the surface
(B-48, C-lll, C-ll)
act as signals in
the uptake and
metabolism of
Lipoprotein
vesicle content.
The diameter of
Chylomicrons
ranges from about
100 nm to about
500 nm.
Cholesterol
Triacylglycerols
and Choleseryl esters
Phospholipids like Phosphatidyl
Choline
The remnants of chylomicrons, depleted of most of their triacylglycerols but still containing cholesterol
and apolipoproteins, travel in the blood to the liver, where they are taken up by endocytosis, mediated by
receptors for their apolipoproteins. Triacylglycerols that enter the liver by this route may be oxidized to
provide energy and also to provide precursors for the synthesis of ketone bodies, as described in Biochemistry
studies. When the diet contains more fatty acids in excces than are needed immediately for fuel or as ketone
bodies, the liver converts them to triacylglycerols, which are packaged with specific apolipoproteins into
VLDLs,LDL. The VLDLs,LDL are transported in the blood to adipose tissues, where the triacylglycerols are
removed and stored in lipid droplets within adipocytes. Choleseryl esters and Cholesterol matbolizing
within HDL vesicles have been up taken in liver and extra hepatic cells.
Five blood plasma transport forms of Lipids in Lipoprotein vesicles
Albumin
Fatty acid
and Water
insoluble
drug
transport
80200 nm
Chylomicrons
Chylomicrons
2870 nm
very low density
lipoproteins
VLDL
4
2025 nm
low density
lipoproteins
LDL
812 nm
high density
lipoproteins
HDL
600
Fats ingested in diet
Part III
Bioenergetics and Metabolism
figure 17-1 Processing of dietary lipids in vertebrates. Digestion and absorption of dietary lipids occur in
the small intestine, and the fatty acids released from triacylglycerols are packaged and delivered to muscle and
adipose tissues. The eight steps are discussed in the text.
These products of lipase action diffuse into the epithelial cells lining the intestinal surface (the intestinal
mucosa) (step (3)), where they are reconverted to triacylglycerols and packaged with dietary cholesterol and
specific proteins into lipoprotein aggregates called chylomicrons (Fig. 17-2; see also Fig.17-1, step (4)).
Apolipoproteins are lipid-binding proteins in the blood, responsible for the transport of triacylglycerols,
phospholipids, cholesterol, and choles-teryl esters between organs. Apolipoproteins ("apo" designates the
protein in its lipid-free form) combine with lipids to form several classes of lipoprotein particles, spherical
aggregates with hydrophobic lipids at the core and hydrophilic protein side chains and lipid head groups at the
surface. Various combinations of lipid and protein produce particles of different densities, ranging from
chylomicrons and very low-density lipoproteins (VLDL) to very high-density lipoproteins (VHDL), which
may be separated by ultracentrifugation. The structures and roles of these lipoprotein particles in lipid transport
we have studied now.
The protein moieties of lipoproteins are recognized by receptors on cell surfaces. In lipid uptake from the
intestine, chylomicrons, which contain apolipoprotein C-II (apoC-II), move from the intestinal mucosa into
the lymphatic system, from which they enter the blood and are carried to PS* (phospho lipase) and adipose tissue
(Fig. 17-1, step (5)). In the capillaries of these tissues, the extracellular enzyme lipoprotein lipase, activated by
apoC-II, hydrolyzes triacylglycerols to fatty acids and glycerol (step (6)), which are taken up by cells in the
target tissues (step (7)). In muscle, the fatty acids are oxidized for energy up to CO2, H2O, in adipose tissue,
they are reesterified for storage as triacylglycerols (step (8)) and storing in fatt droplets.
5
R C
O
O H , the resulting cholesteryl ester is apolar.
When the alcohol group of cholesterol is attached to an acyl
Cholesterol with hydroxyl group HO- occurs in membranes but cholesteryl esters do not.
22
22
Cholesteryl ester is
H HH
H HH
20
20
21
23
21
23
deposed and stored in
H HH
A Cholesterol H HH
B Cholesteryl ester
hepatic and extrahepatic
18
18
H HH
H HH
24
24
19
19
26
26
17
17
12
12
(like leucocytes) cells as
16
16
25
25
H HH 11 13
H HH 11 13
D
C
C 14 D 15
15
small droplets.
27
27
14
HO
H HH
9
1
8
10
2
A5 B7
3
6
4
O
R C
Steroid alcohol = cholesterol
H HH
9
1
8
10
2
A5 B7
3
6
4
O
cholesteryl ester
Cholesterols make up 1/3 mass fraction of membrane masas, but cholesteryl esters do not.
FIGURE I.3. Cholesterol and cholesteryl ester.
A. Cholesterol. The four rings of the steroid are labeled A, B, C and D.
The methyl groups–CH3 labeled 18 and 19 are called angular methyl groups.
Note the double bond between carbon atoms 5 and 6 and alcohol HO- at carbon 3.
B. Cholesteryl ester. An acyl group is attached to the alcohol HO- via a low-energy ester bond -O-.
H HH
both angular methyl groups
H
H
H
H
H HH
H
H
H HH
HO
cholesterol is roughly planar with both angular methyl groups above the plane of the molecule
O
H
H
2
O
R''
C H
H C
H
O
O
O
P
O
H
2
O
1
O
H
H
C
O
O
P
H
O
O
C
2
H
H
H H
N
C
+
C
H R''
H
H C
H
O
H
H
3
+
O
H
2
O
H
H
O
R'
C
1
C O
H C
H
3
H
H
O
O
CH2 CH2 N
P
O
O
H
O
O
H
O
H
H
+
3
R''
H
O
H
H
H
H
R'
1
2
O
H
C H
O
a cephalin (a phosphatidylethanolamine+)
H
H
CH2 CH2 N H
P
O
a lecithin (a phosphatidylcholine+)
R'
C
1
C O
C H
O
H
H
H H H
O
H
R'
C
C H
H
with second hydroxyl group HO- second ester bond -O-
C O
3
C
second alcohol
O
HO
O
H
R''
Figure I.4. Phosphatidate.
Acyl groups are attached in ester linkage at C 1 and C 2
and phosphate is attached in ester linkage at C 3.
Each of these bonds is of the low-energy variety.
C O Low energy ester
3
C
C R'
1
H
O
O P O
O
6
OH
OH
1
2
OH
5
4
HO
O
3
H
Lysophosphatidylcholine+
Phosphatidylinositol
FIGURE I.4. Representative glycerolipids. A nonsystematic name for phosphatidylcholine is lecithin.
The 1-alkyl phospholipids and platelet activating factor contain an alkyl group attached via an ether bond to the
R C
C 1 carbon atom. The other compounds contain an acyl group
6
O
O H
attached to alcohol HO- at C 1.
B. Sphingolipids
Sphingolipids are derivatives of sphingosine, an amino alcohol.
CH3
(CH2 )12
H
O
H
H
N
H
H
+
3
C
4
H
H
2
H
H
O
1
R C
O
3
4
H
N
H
2
H
O
H
1
H
H O
H
O
H
CH3
(CH2)12
3
4
H
N
O HHOH
O
H
R C
O
O
H
H
H
O
O
P
O
H
Ceramide
CH3
(CH2)12
H
H
H
H
H
C
4
C
H
2
Sphingosine
O
3
H
N
O
1 H
H
R C
C
H
CH3
(CH2)12
H
O
H
H
2
H
H H
O
H
1
H
H
H
N
O
Glucosylceramide (cerebroside)
oligosaccharide ceramide (ganglioside)
H H H
O
O
H
H
H
P
OH
+
H
H
Sphingomyelin
FIGURE I.5. Sphingosine and representative sphingolipids.
Sphingosine is a C18 compound with hydroxyl groups —OH on C1 and C3,
an amino group —NH3+ on C2 and a trans double bond = at C4.
Eicosanoids: Call and Name the all four Eicosanoids!
Almost all mammalian cells except erythrocytes produce one or more of eicosanoids,
20-carbon compounds (Greek eikosil , "twenty"), that include such representatives:
prostaglandins
(PGs),
prostacyclins
(PGIs),
thromboxanes
(TXs) and
leukotrienes
(LTs).
Prostaglandins PGA2, PGE1, PGE2, PGE3, PGF2 , PGG2, PGH2, Prostacyclin PGI2.
Thromboxanes TXA2, TXB2 and Leukotriene LTE4 .
To draw the structures of C20 carbon atoms initial compounds-carboxyl acids for EICOSANOIDS
9
8
7
2
6 5 4 C 1
C
10
11
O
OH
15 17
13
H H
20
16
18
12 14
19 H
prostanoate 20 C chain with cross-link
between
9
10
11
8
C8
7
—C12
. Saturated carboxylic
acid.
2
6 5 4 C 1
C
9
7
8
2
5 4 3 C
6
10
11
13
12 14
15
16
17
18
O H
C1
O
19 H 20
H
H
arachidonic acid 20 C chain with cross-link
between C8 —C12 . Unsaturated carbonic acid
with 4 four double bonds = .
O
9
O
8
7
6
10
15 17
13
H H
20
16
18
12 14
19 H
11
13
12 14
2
5 4 3 C
15
16
17
18
O
C1
O
19 H 20
H
H
blood plasma pH =7.36
prostanoate 20 C chain with cross-link
arachidonic acid 20 C chain with cross-link
between C8 —C12 . Saturated carboxylic
between C8 —C12 . Unsaturated carbonic acid
acid salt.
salt with 4 four double bonds = .
7
Lipid peroxidation is radical initiated chain reaction providing a continues supply of free radicals that initiate
further peroxidation. The whole process (chain type reaction) is depicted as follows:
Important is to know that water is source medium of peroxidation agents metal(n)+,
, Aldehyde OxRed.
Let us start from arachidonic acid salt 4 double bond = ω6 fatty acid Eicosanoid in Membrane Bilipid Layer:
(1) Initiation in life organisms at presence of oxygen O=O , which oxidizing power as for agent is strong and
depends on concentration, and is consequently working under three different factors (1., 2., 3.) in life bodies:
1. Production of radicals R• from precursor RH by metal(n)+ ion as Oxidant (Fe3+, Mn4+, Cu2+, etc).
R÷O÷O÷H + metal(n)+ (which transfer H+ and e- to Oxidant)
peroxide R÷O÷O• + metal(n--1)+ + H+
2. Production of radicals R• from precursor RH at presence of oxygen O=O high energy radiation (
(separate and transfer H• together with e- as Oxidant)
R÷H +
)
(H+ + e- = H• radical)
R• + H•
3. Production of radicals R• from precursor RH at presence of Enzymes Aldehyde OxydoReductases in
peroxisomes at presence of oxygen O=O, which concentration in cytosolic water is [O2]=6•10-5M.
2R-C=O-H + O=O
peroxide 2RC÷O÷O• + 2H•
(Aldehyde OxydoReductase
(2) Propagation (new radical R• production):
peroxide R÷O÷O• + R÷
R•
+ O=O
peroxide R÷O÷OH + R•
peroxide R÷O÷O• , etc.
(3) Termination (recombination radical R• attraction and joining):
peroxide R÷O÷O• + peroxide R-O-O•
peroxide R÷O÷O• + R•
R• + R•
H 20 19
H
H
17
18
16
15
14
13
peroxide R÷O÷O÷R + O=O
peroxide R÷O÷O÷R
9
12 11
6
8
7
10
Eicosanoate
radiation energy E ~h 
H
O
5
3
4
H
2
1
R H
O
H hydrogen radical
O
R• H•
H
O
H
H
H
H
O
H
R•
O
H
H
H
O O
O O
O O
O
H
H
O
H
R÷O÷O•
O
H
RH
R
O
H
O O
H
H
O O
H
Malonil aldehyde
Endoperoxide
Hydro peroxide ROOH does undergo oxidation.
FIGURE I. 5. Lipid peroxidation. The reaction is initiated R• by high energy radiation (
),
(n)+
Aldehyde OxydoReductase or by heavy metal ions metal .
Malonil aldehyde is only formed by fatty acids with 3 or more >3 double bonds and is used as
measure of lipid peroxidation together with ethane from the terminal 2-carbon of
fatty acids
and pentane from the terminal 5-carbon of
fatty acids.
8