470
ERIC E. CONN
energy compound formed prior to ATP. Slater emphasizes that a stimulation of apparent ATP-ase activity will result if Reaction 10 is reversed
and this reaction is coupled with Reaction 19.
ATP + I + X ^—± X~I + ADP + P»
(10R
X~ I + H 2 0
> X + I
(19
ATP + H 2 Q
> ADP + Pi
Sum
Cooper and Lehninger (174) also account for the action of uncoupling
agents by a reversal of Reaction 13 and a coupling of Reaction 13R with
the hydrolysis of the phosphorylated intermediate (Reaction 20).
ATP + I^± ADP + P~7
(13R)
P~Z + H 2 0 -» Fi; + I
(20)
ATP + H 2 0 -> ADP + P t
Sum
Thus, the "ATP-ase" activity stimulated by dinitrophenol is considered
to "represent a hydrolytic dysfunction" (184) of the enzyme system
catalyzing transfer of phosphate between ADP and a primary highenergy phosphate compound (P^i) formed during oxidative phosphorylation. In this connection Hulsmann and Slater have recently
observed four different enzyme systems in heart mitochondria which
accomplish the hydrolysis of ATP. They suggest that three of these,
which are stimulated in varying degrees by dinitrophenol, are related to
the three dinitrophenol-sensitive steps in the respiratory chain phosphorylation (173).
Thyroxine (185), dicumarol (76, 184), and Ca
2+ (186) are among
other substances known to affect oxidative phosphorylation. Although
the exact manner in which dinitrophenol acts is not known, there is
good evidence to support the belief that Ca
2+ ions and thyroxine do not
function in the same manner when they "uncouple" phosphorylation.
For example, Ca
2+ and thyroxine have been shown to cause swelling of
intact rat liver mitochondria, whereas dinitrophenol and dicumarol inhibit spontaneous swelling of these particles (187). Also, dinitrophenol
(75) and dicumarol (75) inhibit oxidative phosphorylation carried out
by the submitochondrial particles of Lehninger, while thyroxine (188)
and Ca
2+ (75) do not. The effect of these and other uncoupling agents
has been reviewed (13, 46, 185).
The exchange of ATP with inorganic phosphate labeled with P
32 has
been investigated in rat liver mitochondria (189, 190) and correlated
with ATP-ase activity in submitochondrial particles (174). On the basis
of these observations Cooper and Lehninger have elaborated the scheme
proposed earlier by Lehninger (137) for oxidative phosphorylation.
Their scheme, which has been described above, accounts for the role of
ATP, ADP, and inorganic phosphate in the exchange reactions with
ERIC E. CONN
energy compound formed prior to ATP. Slater emphasizes that a stimulation of apparent ATP-ase activity will result if Reaction 10 is reversed
and this reaction is coupled with Reaction 19.
ATP + I + X ^—± X~I + ADP + P»
(10R
X~ I + H 2 0
> X + I
(19
ATP + H 2 Q
> ADP + Pi
Sum
Cooper and Lehninger (174) also account for the action of uncoupling
agents by a reversal of Reaction 13 and a coupling of Reaction 13R with
the hydrolysis of the phosphorylated intermediate (Reaction 20).
ATP + I^± ADP + P~7
(13R)
P~Z + H 2 0 -» Fi; + I
(20)
ATP + H 2 0 -> ADP + P t
Sum
Thus, the "ATP-ase" activity stimulated by dinitrophenol is considered
to "represent a hydrolytic dysfunction" (184) of the enzyme system
catalyzing transfer of phosphate between ADP and a primary highenergy phosphate compound (P^i) formed during oxidative phosphorylation. In this connection Hulsmann and Slater have recently
observed four different enzyme systems in heart mitochondria which
accomplish the hydrolysis of ATP. They suggest that three of these,
which are stimulated in varying degrees by dinitrophenol, are related to
the three dinitrophenol-sensitive steps in the respiratory chain phosphorylation (173).
Thyroxine (185), dicumarol (76, 184), and Ca
2+ (186) are among
other substances known to affect oxidative phosphorylation. Although
the exact manner in which dinitrophenol acts is not known, there is
good evidence to support the belief that Ca
2+ ions and thyroxine do not
function in the same manner when they "uncouple" phosphorylation.
For example, Ca
2+ and thyroxine have been shown to cause swelling of
intact rat liver mitochondria, whereas dinitrophenol and dicumarol inhibit spontaneous swelling of these particles (187). Also, dinitrophenol
(75) and dicumarol (75) inhibit oxidative phosphorylation carried out
by the submitochondrial particles of Lehninger, while thyroxine (188)
and Ca
2+ (75) do not. The effect of these and other uncoupling agents
has been reviewed (13, 46, 185).
The exchange of ATP with inorganic phosphate labeled with P
32 has
been investigated in rat liver mitochondria (189, 190) and correlated
with ATP-ase activity in submitochondrial particles (174). On the basis
of these observations Cooper and Lehninger have elaborated the scheme
proposed earlier by Lehninger (137) for oxidative phosphorylation.
Their scheme, which has been described above, accounts for the role of
ATP, ADP, and inorganic phosphate in the exchange reactions with