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Transport in organism
Transports
Transport across membranes

Electron transport

Nutrient transport
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Transport across membranes
Biological membranes
Composition: lipid bilayer (glycerolphospholipids, cholesterol,
glycosphingolipids, proteins) peripheral and integral
Cell protection and building function, compartmentization
Highly selective permeability
Regulation of metabolic pathways
Impermeable to ions and polar molecules
They can have specific receptors for signal molecules
In some of them are integratet enzymes or enzymes systems
3
Basic function of all membranes is
selective transport across them
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Mechanism of transport


Nonmediated transport
Nonspecific permeation simple diffusion

Mediated transport
Passive (facilitated diffusion)
Active, against concentration gradient
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Simple diffusion
The direction of movement of solutes by
diffusion is always from a higher to a lower
concentration and rate is described by Fick

Ficks first law of diffusion:
A net movement of molecules from one
compartment to another will continue until the
concentration in each is at a chemical equilibrium
Solution in membrane lipids and redistribution on the reverse side
of membrane (some lipophilic compounds, gases dissolved in
water O
2
, N
2
, H
2
, CO
2
)
Permeability through irregularity in lipids bilayer (ca 10% of H
2
O)
Diffusion by pores in membrane
Movement by hydrophilic channels
gap junction
konexin
transfer of molecules and ions between 2 neighbouring cells
Simple diffusion
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Mediated transport
Active Passive
Mediated transport
Passive
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Mediated transport
Transfer of molecules in complex with
transport systems

Properties:
Speed and specificity of transport
Saturation of kinetics
Possibility of competitive inhibition
Possibility of chemical inactivation

Typical example is transport of glucose into
erythrocytes
v
[S]
A
B
Simple diffusion - A
Transport of glc into erythrocytes - B
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Ionophores - mediated transport
Ionophores - organic molecules with different structure, often antibiotics,
they increase membrane permeability for some ions
- passively transport ions via membrane until the concentration
in each side is at a chemical equilibrium

Ionophores
Valinomycin (cyclic peptide)
Transfer of K
+
(10
4
ions / s)


Gramicidin (linear peptide helix)
Transfer of K
+
(10
7
ions / s)

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Glucose transport into
muscle and fat cells
Glc binds to the protein on one face of the membrane
A conformational change closes the first binding site and expose
the binding site on the other side of the membrane
Glucose dissociates from the protein
The transport cycle is completed by the reversion of the glc
transporter to its initial conformation in the absence of bound glc

Glucose transport into
muscle and fat cells
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Membrane channels

Passive, but specific systems
Mainly for cations
Transport due to concentration gradient or gradient of electrochemical
potential
Some channels are always open (eg. some porines)
Mostly regulated:
by membrane depolarization
(ions channels for K
+
a Na
+
in nerve impulses)
by binding of specific ligand (eg. acetylcholin - neurochemistry)
by mechanical pressure (ions channels in special cells of inner ear)
Gate is principal regulator, open and closed position
Mediated transport
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Mediated transport
Active Passive
Mediated transport
Active
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Significance of the active transport
Maintain intracellular volume
Maintain ion composition (optimal osmotic condition
in a cell)
Form and keep ion gradient
Elimination of waste products of metabolism

Active transport
Transport against gradien (chem., el.)
Supply of energy is needed
Hydrolytic cleavage of molecules with high transfer
potential ATP




Primary active transport
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Na/K-ATPase


Energy 1 ATP


transfer 3 Na
+
and 2 K
+
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Primary active transport:
Na/K-ATPase
in
out
ATP 3 Na
+
3 Na
+
2 K
+
2 K
+ ADP P
i
Ca-ATPase
Actively pumps Ca
2+
out of the cytosol at the expense of
ATP hydrolysis
Activation by calmodulin

H,K-ATPase of gastric mucosa
Secretion of H
+
- antiport with K
+
Cl
-
for HCl formation is transfer by different transporter
via symport with K
+
Primary active transport
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Secondary active transport
Many active transport processes are not directly
driven by the hydrolysis of ATP

Characterization by co-transport
Antiporter
Symporter
Secondary active transport
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Transport in mitochondrion
Structure of mitochondrion
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Mitochondrial membrane
inner membrane
76 % proteins 24 % lipids

in comparison with:
Hepatocytes membrane
46 % proteins 52 % lipids
Erythrocytes membrane
49 % proteins 43 % lipids
MI membrane - outer
Outer membrane contains protein porin,
nonspecific pores
transport of molecules (up 10 kDa) by
diffusion
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MI membrane - inner
High content of proteins - enzymes and transport
proteins
permeable only for O
2
, CO
2
, H
2
O
impermeable for acetyl-CoA, oxaloacetate,
nikotinamide nucleotides,...
other metabolites (low-molecular products and
substrates) and some ions have regulated
permeability
NADH produced by glycolysis must be transported into
MI
metabolites formed in MI (eg. oxaloacetate, acetyl-CoA)
must be transported into cytosol biosynthesis
ATP formed in MI must be transported into cytosol,
where is most reactions which use it
ADP and P
i
must be transported from CY into MI
(substrates of oxidative phosphorylation)
Mitochondrial transport systems
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Transport of H from NADH from CY into MI
Glycerol-phosphate shuttle
Malate-aspartate shuttle

Transport of oxaloacetate into CY
Malate-aspartate shuttle
Mitochondrial transport systems
Glycerol-phosphate shuttle
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Malate-aspartate shuttle
Transport of Ac-CoA to cytosol
Acetyl-CoA oxidative decarboxylaion of pyruvate, FA
oxidation
Low consumption of ATP acetyl-CoA is stored in form
of fat transport to cytosol is needed
Acetyl-CoA enters into cyt. as citrate transport
system for tricarboxylic acids
in cytosol:


ATP + citrate + CoA acetyl-CoA + oxaloacetate + ADP + P
i
ATP-citratelyase
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Transfer of Ac-CoA from MI to CY
Ac-CoA as a key intermediate
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ADP-ATP translocase
ATP formed in MI (ox.phosph.) cytosol
biosynthesis, muscle contraction, act. transport
Antiport ATP-ADP
ADP-ATP translocase
a dimer
identical subunits
one binding site, competition of ATP with ADP
two conformation
binding site open into matrix MI
binding site open into extracellular space