1

Membranes
Outline: Key concepts:
Structure and composition of Fluid mosaic model of membranses
membranes Three major classes of transport
Structure and function of systems
membrane proteins Consequences of uncoupling of
Transport across membranes oxidative phosphorylation
Uncoupling of oxidative
phosphorylation

Web Resources: https://themedicalbiochemistrypage.org/membranes.php;

https://www.cff.org
 2
Membranes

• Lipid-based structures that form pliable sheets

• The sheets are continuous closed 3-D structures
• Composed of a variety of lipids and proteins
• Carbohydrates (via glycosylation) and other components are typically also
present
• All cells have a cell membrane
• Separates the cell from its surroundings
• Eukaryotic cells have several types of internal membranes
• Separate the internal space into compartments
 3
Membranes in a eukaryote cell

Cytosol
 4
Typical structural features of membranes
• Sheet-like flexible structure
• ~30 Å (~3 nm) thick
• Composed of two leaflets of lipids
• Termed the "bilayer"
• Stabilized by noncovalent forces, especially hydrophobic interactions
• Some protein molecules span the lipid bilayer
• Asymmetric
• Some lipids are found preferably “inside”, some "outside"
• Carbohydrate moieties are always outside the cell
• Electrically polarized
• Inside negative
• –60 mV is a typical voltage gradient, but some membranes have a
greater electrical gradient
 5
The lipid bilayer of membranes

• Consists of two leaflets of lipid monolayers

• Hydrophilic head groups interact with water
• Hydrophobic fatty acid tails are packed inside
• One leaflet faces the "outside", the other the "inside"

The
two
bilayers
 6
The fluid mosaic model of membranes
 7
The fluid mosaic model of membranes
 8
Different membranes have specific lipid compositions

The lipid composition varies in the membranes of different organisms, tissues,

and organelles
• The lipid/protein ratio varies
• The type of phospholipid varies
• The abundance and type of sterols varies (sterols = steroids with a -OH group)
• E.g., prokaryotes do not have sterols
• Cholesterol is important in the plasma (= cell) membrane of animal cells, but
virtually absent in mitochondria
 9
Some phospholipids found in membranes: Phosphatidyl-

serine ethanolamine choline

The glycerol moiety is shown in red. Note the ionic hydrophilic ends compared to
the long-aliphatic hydrophobic ends.
 10
Phosphatidylethanolamine Phosphatidylcholine
Non-polar in purple
Polar in blue
Phospholipids
 12
Examples of proteins in membranes
• Receptors: detecting signals from outside
• E.g., insulin receptor (see figure below)
• Channels, gates, pumps for metabolites and ions
• E.g., glucose transporter (see figure below)
• Enzymes
• E.g., ATP synthase, complexes I, II, III, IV
 13
Model of a membrane

~30 Å

Often form alpha helix to increase number of H bonds in polypeptide backbone

1.5 Å per amino acid in an alpha helix (= the "rise")
~20 amino acids per ~30 Å across the lipid layer of a membrane.

~30 Å
= ~20 amino acids
1.5 Å/a.a.
 14
Major types of transport systems

A B C D E

A B C D E
Uniport Symport Antiport
 15
Some lipophilic cmpds. can traverse a membrane without a transport system
Transport of ATP/ADP and Pi across the inner mitochondrial membrane
 First law of thermodynamics:

You must end up with as much energy as you started with; i.e., you cannot
create or destroy energy. This obeys the law of conservation of energy. Result:
A perpetual-motion machine is impossible in this universe. You cannot win or
lose -- only break even.

What do these two pictures have in common?

 Heat generation by uncoupled mitochondria

Uncoupled = respiration occurs, ATP synthesis does not; i.e., respiration (=

ETC) is "uncoupled" from phosphorylation (= ADP + Pi → ATP)
 Heat generation by uncoupled mitochondria

Important in brown adipose tissue (brown because so many mitochondria and rbc's)
E.g., newborn humans, fawns (under hormonal control by epinephrine)
 Heat generation by uncoupled mitochondria

Net result: P/O ratios (= ATP/2 ε-) decrease, potentially so far that death can
occur
 21
Two chemical uncouplers of
oxidative phosphorylation
+ H+
Note that BOTH the
acid and base forms
have extensive
2,4-Dinitrophenol
resonance. Hence,
even the charged base
form is hydrophobic due
to delocalization of the
negative charge.

Cytosol Matrix + H+
UH UH

U- U- Carbonylcyanide-p-trifluoromethoxy-
+ + phenylhydrazone (FCCP)
H+ H+
 22
Why is the base form of 2,4-dinitrophenol lipophilic? Resonance

→ + H+

etc.

The negative charge on the base form is so delocalized that the

lipids in the membrane bilayer do not "see" it. Organic uncouplers
are almost always colored. Why?
Some common uncouplers: Note the extensive resonance in all these uncouplers

The pKa of these weak acids is in the range from 3.9 to 6.8.
 24
A commonly used chemical uncoupler of oxidative phosphorylation

Note that BOTH the

acid and base forms
have extensive + H+
resonance. Hence,
even the charged base
form is hydrophobic due
to delocalization of the 2,4-Dinitrophenol
negative charge.

Cytosol Matrix
UH UH

U- U-
+ +
H+ H+
Death due to hyperthermia
A simplified view of uncoupling of oxidative phosphorylation
 A nice explanation of uncoupling of oxidative phosphorylation

The process of uncoupling of oxidative phosphorylation: In normal oxidative phosphorylation,

electrons donated by NADH are shuttled along a series of proteins in the inner mitochondrial
membrane known as the electron transport chain. Through a series of oxidation reduction reactions
within complexes I, II, III, and IV, protons are pumped against their concentration gradient into the
intermembrane space. This process creates potential energy that under normal circumstances is
converted to ATP through ATP synthetase. Uncoupling occurs when this potential energy is lost, either
through transport of protons through UCP or by chemicals that chaperone protons directly through the
inner mitochondrial membrane. Unable to provide useful work (i.e., make ATP), the potential energy is
converted to heat (because of the law of conservation of energy). Pi, inorganic phosphate.
https://www.researchgate.net/figure/Uncoupling-Process-of-uncoupling-of-oxidative-phosphorylation-In-normal-oxidative_fig2_7539438