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LPIDOS

Molculas biolgicas definidas por su baja


solubilidad en agua y alta solubilidad en
solventes no polares
Su insolubilidad en agua contribuye a que
sean difciles de digerir, transportar y
metabolizar
Molculas seleccionadas evolutivamente
como reservorio energtico

HIDROFBICOS: solo grupos no polares. (Permite a


las membranas actuar como barrera a ms molculas
polares)
*

polar, more amphipathic lipids

ANFIPTICOS: grupos polares y no polares

LPIDOS
1. cidos grasos
2. Triacilgliceroles
3. steres de ceras
4. Fosfolpidos
5. Esfingolpidos
6. Isoprenoides

cidos Grasos
CH3(CH2)14-COONo-polar

polar

CABEZA

Ionizado en condiciones
fisiolgicas, generalmente
esterificado

COLA

14 24 C

cidos grasos

SATURADOS E INSATURADOS

MONOINSATURADO

cidos Grasos
cido Hexadecanoico

16:0

cido cis-9-Octadecenoico

18:1(D9 )

AC. GRASOS SATURADOS

MOLCULAS EXTREMADAMENTE FLEXIBLES LIBRE ROTACIN C-C


IMPEDIMENTO ESTRICO CONFORMACIN LINEAL MS ESTABLE

AC. GRASOS INSATURADOS

DOBLE ENLACE PROVOCA TORSIN AGRUPACIONES FLUIDAS


se empacan con menor densidad

AC. GRASO SATURADO AGRUPACIONES MS RGIDAS

cido esterico 18:0


Tf = 69.6 oC

cido oleico
18:1(D9 )
Tf = 13.4 oC

metilo terminal

3
2

C
1

fatty acid with a cis-D9


double bond

cidos grasos esenciales


Los cidos linoleico y linolnico son esenciales y deben obtenerse de
los alimentos.
El cido linoleico (18:2w-6) y sus derivados, as como el cido araquidnico
A
(precursor de las prostaglandinas) se denominan
cidos grasos omega 6.
El cido linolnico (18:3w-3) y sus derivados, como el cido eicosapentanoico EPA
(20:5w-3) y docosahexanoico DHA (22:6w-3) son los cidos grasos omega 3.

Triacilgliceroles:
steres de glicerol

Fatty
acid

ESTERIFICACIN
Sntesis de
Formation
of un
an ster
ester:
O
R'OH + HO-C-R"

O
R'-O-C-R'' + H2O

Esterificacin de un cido carboxlico

ESTERIFICACIN LPIDO

=O

H2O

AC. GRASO + GLICEROL MONOACILGLICEROL


MONOACILGLICEROL: GLICEROL ESTERIFICADO EN
EL CARBONO 1

TRIACILGLICEROL SIMPLE: 3 CADENAS AC. GRASOS IGUALES


Ejemplos: tristearoylglycerol (tristearin) y trioleoylglycerol (triolein)

TRIACILGLICEROL MIXTO: 1 O MAS


CADENAS AC. GRASOS DIFERENTE.
Ms abundantes
Ejemplo: 1-miristoil 2-estearil 3palmitoil glicerol

Saponificacin
O
O CH2 OCR
saponification
+
3
N
aOH
RCOCH
O
CH2 OCR
A triglyceride
( a triester of glycerol)

CH2 OH
CHOH

O
+
3 RCO N a

CH2 OH
1,2,3-Propanetriol S odium soaps
(Glycerol; glycerin)

Los triacilgliceroles son la principal forma de almacenamiento


y transporte de los cidos grasos.
Son molculas hidrofobicas que se fusionan en pequeas
gotas anhidras dentro de las clulas: adipocitos.
Los triacilgliceroles
son molculas menos
reducidas y liberan
ms electrones por
molcula cuando se
oxidan liberan ms
energa cuando se
degradan
Los triacilgliceroles funcionan como aislantes trmicos. La
grasa es un mal conductor del calor por lo que impide su
prdida

Los lpidos son un grupo de biomolculas qumica y


estructuralmente diverso. Son componentes o sustancias celulares
insolubles en agua y que pueden ser disueltos en solventes no
polares (ter, cloroformo y acetona).
La mayora de los cidos grasos, cadena hidrocarbonada de
varios lpidos, tienen un nmero par de tomos de carbono (1224); pueden ser saturados o insaturados, con dobles enlaces
siempre en configuracin cis.
Los triacilgliceroles (o grasas neutras) son molculas
formadas por tres cidos grasos esterificados a los tres grupos
hidroxilo del glicerol. Pueden ser simples: formados por un solo
tipo de cido graso o mixtos: formados por dos o tres tipos
distintos de cidos grasos.
Los triacilgliceroles se almacenan en forma de grasas y son
una fuente abundante de energa.

steres de ceras

Fosfolpidos

Componente importante
de la membrana mitocondrial interna

(lecitina)

(cefalina)

Glicerofosfolipido antignico

El c. graso en el C1 del glicerofosfolpido est


sustituido por una grupo alquilo insaturado unido
por un enlace ter a la molcula de glicerol.
Abundantes en tejido nervioso y msculo cardico.

El c. graso en el C1 del glicerofosfolpido est sustituido por


una grupo alquilo saturado unido por un enlace ter a la
molcula de glicerol. El C2 est esterificado a un residuo
acetilo. Se une a receptores de superficie y desencadena
potentes eventos trombolticos e inflamacin aguda. Estimula
la agregacin plaquetaria y la liberacin de serotonina

Esfingolpidos
ceramida

fosforilcolina

Isoprenoides

Isopreno
Terpenos y Esteroides

Esteroides

Esteroides

Esteroides

Terpenos

Terpenos

Cuando los fosfolpidos se dispersan


en agua forman micelas. Los
grupos hidrfilicos se disponen
hacia la parte acuosa y la parte
hidrfoba de cada molcula hacia el
interior. Las suspensiones que
contienen este tipo de micelas son
muy estables.

Bilayer

Spherical Micelle

Los lpidos anfipticos pueden tambin dispersarse por una superficie


acuosa pudindose formar, si la cantidad es la adecuada, bicapas. En
particular entre dos compartimentos acuosos. La bicapas lipdicas
poseen caractersticas similares a las de las membranas celulares: son
permeables al agua pero impermeables a los cationes y aniones y
son tambin malas conductoras elctricas. las membranas celulares
son, esencialmente, bicapas lipdicas.

Membrane fluidity:
The interior of a lipid bilayer is
normally highly fluid.

liquid crystal

crystal

In the liquid crystal state, hydrocarbon chains of


phospholipids are disordered and in constant motion.
At lower temperature, a membrane containing a single
phospholipid type undergoes transition to a crystalline
state in which fatty acid tails are fully extended, packing
is highly ordered, & van der Waals interactions between
adjacent chains are maximal.
Kinks in fatty acid chains, due to cis double bonds,
interfere with packing in the crystalline state, and lower
the phase transition temperature.

HO

Cholesterol

Cholesterol
in membrane

Cholesterol inserts into bilayer membranes with its


hydroxyl group oriented toward the aqueous phase &
its hydrophobic ring system adjacent to fatty acid
chains of phospholipids.

The OH group of cholesterol forms hydrogen bonds


with polar phospholipid head groups.

Fluidez de la Membrana
Interaction with the relatively rigid cholesterol
decreases the mobility of hydrocarbon tails of
phospholipids.

Cholesterol
in membrane

But the presence of cholesterol in a phospholipid membrane


interferes with close packing of fatty acid tails in the crystalline
state, and thus inhibits transition to the crystal state.
Phospholipid membranes with a high concentration of
cholesterol have a fluidity intermediate between the liquid
crystal and crystal states.

Two strategies by which phase changes of membrane


lipids are avoided:
Cholesterol is abundant in membranes, such as
plasma membranes, that include many lipids with
long-chain saturated fatty acids.
In the absence of cholesterol, such membranes would
crystallize at physiological temperatures.
The inner mitochondrial membrane lacks cholesterol,
but includes many phospholipids whose fatty acids
have one or more double bonds, which lower the
melting point to below physiological temperature.

Membranas
Lateral mobility of a lipid, within the plane of a
membrane.
High speed tracking of individual lipid
molecules has shown that lateral movements
are constrained within small membrane
domains.
Hopping from one domain to another occurs
less frequently than rapid movements within a
domain.
The apparent constraints on lateral
movements of lipids (and proteins) has been
attributed to integral membrane proteins,
anchored to the cytoskeleton, functioning as a
picket fence.

Lateral Mobility

Flip-flop of lipids (from one half of


a bilayer to the other) is normally
very slow.

Flip Flop

Flip-flop would require the polar head-group of a lipid to


traverse the hydrophobic core of the membrane.

The two leaflets of a bilayer membrane tend to differ in


their lipid composition.
Flippases catalyze flip-flop in membranes where lipid
synthesis occurs.
Some membranes contain enzymes that actively transport
particular lipids from one monolayer to the other.

peripheral
Membrane proteins
may be classified as:
peripheral
integral
having a lipid
anchor

lipid
anchor

lipid bilayer

integral

Membrane
Proteins

Peripheral proteins are on the membrane surface.


They are water-soluble, with mostly hydrophilic surfaces.
Often peripheral proteins can be dislodged by conditions
that disrupt ionic & H-bond interactions, e.g., extraction
with solutions containing high concentrations of salts,
change of pH, and/or chelators that bind divalent cations.

lipid
anchor

O
H 3C

membrane

(CH2)14

palmitate

O
S

CH2

C
CH

cysteine
residue

NH

Some proteins bind to membranes via a covalently


attached lipid anchor, that inserts into the bilayer.
A protein may link to the cytosolic surface of the plasma
membrane via a covalently attached fatty acid (e.g.,
palmitate or myristate) or an isoprenoid group.

Palmitate is usually attached via an ester linkage to the


thiol of a cysteine residue.
A protein may be released from plasma membrane to
cytosol via depalmitoylation, hydrolysis of the ester link.

CH3

CH3
H3C

CH

CH2

CH2

CH3
CH

CH2

CH2 C

CH

CH2

Protein

farnesyl residue linked to protein via cysteine S

An isoprenoid such as a farnesyl residue,


is attached to some proteins via a
thioether linkage to a cysteine thiol.

lipid
anchor
membrane

peripheral
lipid
anchor

lipid bilayer

integral

Membrane
Proteins

Integral proteins have domains that extend into the


hydrocarbon core of the membrane.
Often they span the bilayer.

Intramembrane domains have largely hydrophobic


surfaces, that interact with membrane lipids.

membrane
Amphipathic detergents
are required for
solubilization of integral
proteins from membranes.

detergent
solubilization

polar
non-polar
Protein with
bound detergent

Hydrophobic domains of detergents substitute for


lipids, coating hydrophobic surfaces of integral proteins.
Polar domains of detergents interact with water.
If detergents are removed, purified integral proteins tend
to aggregate & come out of solution. Their hydrophobic
surfaces associate to minimize contact with water.

Balsas lipdicas:
Complex sphingolipids tend to separate out from
glycerophospholipids & co-localize with cholesterol in
membrane microdomains called lipid rafts.
Membrane fragments assumed to be lipid rafts are
found to be resistant to detergent solubilization,
which has facilitated their isolation & characterization.

CH3
H3 C

O
H2
C

H2
C

CH3

phosphocholine

H2C

sphingosine

OH
H
C

CH

NH

CH

HO

Sphingomyelin

fatty acid

HC

Cholesterol

(CH2 )12
CH3

Hydrogen bonding between the hydroxyl group of


cholesterol and the amide group of sphingomyelin
may in part account for the observed affinity of
cholesterol for sphingomyelin in raft domains.

Proteins involved in cell signaling often associate


with lipid raft domains.
Otherwise soluble signal proteins often assemble in
complexes at the cytosolic surface of the plasma
membrane in part via insertion of attached fatty acyl
or isoprenoid lipid anchors into raft domains.

Integral proteins may concentrate in raft domains via


interactions with raft lipids or with other raft proteins.

Caveolas Son unos pequeas invaginaciones en


la membrana citoplasmtica (45-80 nm), presentes
en la mayora de las clulas eucariotas, que
posteriormente se transforman en vesculas. Su
membrana se caracteriza por poseer una protena
llamada caveolina, adems de protenas perifricas
ancladas a glicosilfosfatidil-inositoles, esfingolpidos
(esfingomielina y glicoesfingolpidos) y colesterol.

caveolae
cytosol

Molculas como la toxina del clera, el cido flico y


otras molculas entran a la clula gracias a las caveolas.
Adems, son tambin un lugar de regulacin de la
comunicacin celular puesto que contienen numerosos
receptores en sus membranas que son eliminados de la
superficie celular como los receptores tirosina quinasa.
Tambin participan en la incorporacin de lpidos,
incluso se han postulado en los mecanismos de
supresin de algunos tumores.