LIPIDS AND CELL MEMBRANES

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LIPIDS AND CELL MEMBRANES (Chapter
12) BIOLOGICAL MEMBRANES ARE FLUID MOSAICS OF
LIPIDS AND PROTEINS In 1972, S. Jonathan Singer
and Garth Nicolson proposed a fluid mosaic model
for the overall organization of biological
membranes. The essence of their model is that
membranes are two-dimensional solutions of
oriented lipids and globular proteins (Figure
11-32) .
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• This proposal is supported by a wide
  variety of experimental observations. The major
  features of the model are
• Most of the membrane phospholipid and glycolipid
  molecules are arranged in a bilayer. This lipid
  bilayer has a dual role it is both a solvent for
  integral membrane proteins and a permeability
  barrier.
• 2. A small proportion of membrane lipids
  interact specifically with particular membrane
  proteins and may be essential for their function.
• 3. Membrane proteins are free to diffuse
  laterally in the lipid matrix unless restricted
  by special interactions, whereas they are not
  free to rotate from one side of a membrane to the
  other.

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Eucaryotic (mammalian) cells contain numerous
distinctive organelles
Although the various organelles have diverse
functions mediated by specific proteins, all of
their membranes basically conform to the Fluid
Mosaic Model
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Phospholipids are the major class of membrane
lipids In eukaryotes, phosphatidylcholine (PC)
is the most abundant
Fatty acyl chains attached at the 1-position (R1)
by O-ester bonds are usually fully saturated
(e.g. palmitate, stearate) Fatty acyl chains
attached at the 2-position (R2) by O-ester bonds
usually unsaturated and contain cis-double bonds
(e.g. oleate, linoleate, arachidonate)
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• Sphingomyelin sphingolipid analogue of PC
• Glycosphingolipids cerebroside/gangliosides

The simplest glycolipid, called a cerebroside,
contains a single sugar residue, either glucose
or galactose.
More complex glycolipids, such as gangliosides,
contain a branched chain of as many as seven
sugar residues. Glycolipids are oriented in a
completely asymmetric fashion with the sugar
residues always on the extracellular side of the
membrane.
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Cholesterol enriched in the plasma membrane (PM)
and precursor of bile salts and steroid hormones
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THE BEHAVIOR OF LIPIDS IN AQUEOUS SOLUTIONS
DETERMINE THE BILAYER STRUCTURES OF CELLULAR
MEMBRANES --Sodium salts of fatty acids (soaps)
for micelles. --The two fatty acyl chains of
phospholipids do not favorably pack into
micelles, but spontaneously form bilayers, the
basic structure of cellular membranes.
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MEMBRANE FLUIDITY IS CONTROLLED BY THE FATTY ACYL
COMPOSITION OF MEMBRANE LIPIDS Melting point can
be Increased by increasing chain length, and
lowered by introducing a cis-double bond.
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LATERAL DIFFUSION OF PHOSPHOLIPIDS IS RAPID
COMPARED TO TRANSVERSE DIFFUSION (FLIP-FLOPPING)
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MEMBRANES PERFORMING DIFFERENT FUNCTIONS
CONTAIN DIFFERENT ARRAYS OF PROTEINS After
membrane isolation, the proteins can be separated
by SDS-polyacrylamide gel electrophoresis
(Stryer-pp.329)
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MEMBRANES CONTAIN TWO MAJOR CLASSES OF
PROTEINS 1. INTEGRAL (INTRINSIC) PROTEINS
REQUIRE DETERGENTS (e. g. TRITON X-100) FOR
SOLUBILIZATION, AND WHEN SPANNING THE LIPID
BILAYER ARE REFERRED TO AS TRANSMEMBRANE PROTEINS
(Exs. a,b and c) 2. PERIPHERAL (EXTRINSIC)
PROTEINS ARE ASSOCIATED WITH MEMBRANE LIPIDS
OTHER MEMBRANE PROTEINS BY ELECTROSTATIC
INTERACTIONS. THIS CLASS CAN USUALLY BE
SOLUBILIZED BY EXTRACTING WITH 1M KCl OR 1M NaCl
(Exs. d and e).
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SOME PROTEINS ARE EMBEDDED IN THE LIPID BILAYER
OF MEMBRANES THROUGH COVALENTLY ATTACHED HYDROBIC
GROUPS (Exs. Thioester and amide (peptide)
linkages)
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MEMBRANE PROTEINS AND LIPIDS ARE FREE TO DIFFUSE
LATERALLY WITHIN THE PLANE OF THE BILAYER. THIS
WAS FIRST DEMONSTRATED BY FRYE AND EDIDIN AT
JOHNS HOPKINS UNIVERSITY (ORIOLE FANS!!!) BY THE
EXPERIMENT ILLUSTRATED BELOW
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THE NUMBER OF TRANSMEMBRANE (MEMBRANE-SPANNING)
DOMAINS IN A MEMBRANE PROTEIN CAN BE PREDICTED
FROM ITS AMINO ACID SEQUENCE BY HYDROPATHY PLOTS
THE HYDROPATHY PLOT FOR GLYCOPHORIN FROM RBCS
PREDICTS ONE TRANSMEMBRANE DOMAIN (Stryer p. 334)
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Cellular membranes are structurally and
functionally asymmetric
Functional asymmetry of sodium pump
(Na/K-ATPase)
Asymmetric orientation of oligosaccharide chains
in glycoproteins and glycolipids In the plasma
membrane
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2X sodium salts of FA Glycerolphosphorylcholin
e
MILD BASE HYDROLYSIS 0.1N NaOH, 0ºC
STRONG ACID HYDROLYSIS 6N HCl, 100 ºC
2X sodium salts of FA 1X Glycerol 1X
Phosphoric acid 1X Choline