Biology Reference
In-Depth Information
systems located in (and on) the inner mitochondrial membrane synthesize ATP
from ADP and inorganic phosphate, P
i
, using the free energy supplied by the
oxidation of NADH to NAD
+
. The whole process is very complex and has not
yet been completely elucidated in my opinion (Ji 1979), despite the fact that
biochemistry textbooks around the world accept the assumption that
chemiosmosis
(i.e., the process of converting
chemical
energy of say NADH to the
osmotic
energy
of the pH gradient across the inner mitochondrial membrane) is responsible for
driving the synthesis of ATP from ADP and P
i
(e.g., see Figs. 21-22 on p. 545 in
[Stryer 1995]). One glaring deficiency of the chemiosmotic hypothesis, for which
P. Mitchell received the Nobel Prize in Chemistry in 1978, is a complete lack of any
enzymologically realistic molecular mechanism that can convert chemical energy
of NADH to the osmotic energy of the pH gradient and associated membrane
potential. The chemiosmotic hypothesis can be represented as:
Mechanism ð?Þ
NAD
þ
þ
NADH
þ
=
2
O
2
!
H
2
O
þ
Proton gradient
(8.8)
1
Proton gradient
ADP
þ
Pi
!
ATP
þ
H
2
O
(8.9)
To provide a chemically realistic molecular mechanisms underlying energy
conversion in Processes
8.8
and
8.9
, an alternative mechanism of oxphos, known
as the
conformon hypothesis
, was proposed in 1972 (Green and Ji 1972a, b; Ji
1974a, b, 1976, 1977, 2000), according to which the free energy conversion
involved proceeds through three main steps:
ETC
z
NAD
þ
þ
H
2
O+
ETC
NADH
þ
=
2
O
2
þ
ETC
!
(8.10)
1
ðETC=TRUÞ
z
ETC
ETC
þ
TRU
TRU
!
þ
(8.11)
z
ATP
TRU
ADP
þ
Pi
þ
TRU*
!
þ
H
2
O+
TRU
(8.12)
where all the macromolecular systems (i.e., molecular machines) are written in bold
letters,
ETC
stands for
electron transfer complexes
(of which there are three
denoted as
I
,
III
, and
IV
) located in the inner mitochondrial membrane, and
TRU
is an abbreviation for “tripartite repeating unit,” the enzyme system consisting
of (1)
F
0
, (2) the oligomycin-sensitivity conferring protein (
OSCP
), and (3)
F
1
, also
called the
ATP synthase
or
Complex V
(see Fig. 1 in Ji 1976).
It is to be noted that, in each step, the enzyme system involved plays a dual role -
as a carrier of free energy denoted by the superscript * and as an enzyme lowering
the energy level of the transition state denoted by the superscript
{
. Thus, a
significant amount of the free energy generated from the oxidation of NADH is
stored in
ETC*
in Process
8.10
, which is thought to be transferred to
TRU*
in
