Biology Reference
In-Depth Information
(a)
(b)
H
O
O
NO
2
HN
O
O
O
NH
O
O
O
O
2
N
OH
O
O
O
O
O
HN
O
O
O
NH
O
O
H
(d)
OH
(c)
COOH
O
OH
OH
OH
OH
O
O
O
OH
OH
OH
NH
2
O
O
O
O
O
CH
3
H
3
C
H
3
C
OH
O
O
H
HO
CH
3
Nystatin A
FIGURE 14.19
Representative examples of ionophores: (a) Valinomycin (b) 2,4-dinitrophenol (c) Nystatin
(d) Crown ether.
Valinomycin
Superficially, valinomycin resembles a cyclic peptide (
Figure 14.19
). However, upon closer
examination the ionophore is actually a 12 unit (dodeca) depsipeptide where amino acid
peptide bonds alternate with amino alcohol ester bonds. Therefore the linkages that hold
the molecule together alternate between nitrogen esters (peptide bonds) and oxygen esters.
The units that comprise valinomycin are D- and L-valine (hence the name 'valinomycin'),
hydroxyvaleric acid, and L-lactic acid. The circular structure is a macrocyclic molecule where
12 carbonyl oxygens face the inside of the structure where they chelate a single K
þ
. The
outside surface of valinomycin is coated with 9 hydrophobic side chains of D- and L-valine
and L-hydroxyvaleric acid. The polar interior of valinomycin precisely fits one K
þ
. The
binding constant for K
þ
-valinomycin is 10
6
while Na
þ
-valinomycin is only 10. This empha-
sizes the high selectivity valinomycin has for K
þ
over Na
þ
. Valinomycin, therefore, has an
oily surface that readily dissolves in a membrane lipid bilayer, carrying K
þ
across the
membrane down its electrochemical gradient.
Valinomycin was first recognized as a potassium ionophore by Bernard Pressman in the
early 1960s
[31,32]
. He reported that valinomycin, a known antibiotic, stimulated K
þ
uptake
andH
þ
efflux frommitochondria. Many studies showed that valinomycin dissipates essential
