188
A. T. MILLER, JR.
lactate: pyruvate ratio has shifted toward a more reduced state, and our
studies on turtle brain indicate that ATP may be normal even when the
NADH: NAD+ ratio is greatly elevated. There are also considerable differences in the response of various cellular oxidation-reduction systems to
hypoxia, some of them changing only when hypoxia is very severe. It
would be of interest to extend these studies to other systems which characterize the oxidation-reduction state in cytoplasmic, mitochondrial matrix
and mitochondrial cristae compartments, as suggested by KREBS [3].
Table 1. Brain chemical changes in normal and polycythemic rats breathing various gas
mixtures
Animals
Het
Gas breathed-9'
Cr P* ATP* L/P
NADH/
(%)
NAD+
Transfused
63
arr
3.09
2.88
14
.12
Controls
49
arr
3.09
2.61
16
.14
Cobalt
66
arr
3.58
2.80
15
.08
Controls
55
arr
3.49
2.87
16
.09
Altitude
76
air
3.64
2.43
17
.12
Controls
54
air
3.66
2.78
17
.12
Transfused
62
4% O2
1.43
2.35
75
.16
Controls
48
4%02
1.29
2.42
72
.14
Cobalt
67
4%02
2.26
2.39
60
.11
Controls
52
4%02
1.54
2.21
66
.14
Altitude
81
4%02
1.99
2.92
46
.15
Controls
55
4% O2
1.72
2.99
51
.17
Cobalt
71
4% O2-5% CO2
3.22
2.59
22
.11
Controls
51
4% O2-5% CO2
2.29
2.17
29
.15
Altitude
77
4% O2-5% CO2
3.05
2.59
14
.14
Controls
54
4% O2-5% CO2
1.95
2.47
31
.19
* pM/gram wet tissue
The most satisfactory indication that a cell is hypoxic might be the
demonstration that it is forced to utilize anaerobic metabolism to a greater
than normal degree, even though the maintenance of normal levels of high
energy compounds is thereby accomplished. This would simplify the problem from the experimental standpoint provided a satisfactory solution of
the interpretation of "lactate increase", "lactate: pyruvate ratio" and
"excess lactate" can be achieved.
In our experiments, tests of brain function showed impairment at levels
of hypoxia which did not reduce the concentration of ATP in the brain.
Much needs to be learned about the chemical basis of brain function de-
A. T. MILLER, JR.
lactate: pyruvate ratio has shifted toward a more reduced state, and our
studies on turtle brain indicate that ATP may be normal even when the
NADH: NAD+ ratio is greatly elevated. There are also considerable differences in the response of various cellular oxidation-reduction systems to
hypoxia, some of them changing only when hypoxia is very severe. It
would be of interest to extend these studies to other systems which characterize the oxidation-reduction state in cytoplasmic, mitochondrial matrix
and mitochondrial cristae compartments, as suggested by KREBS [3].
Table 1. Brain chemical changes in normal and polycythemic rats breathing various gas
mixtures
Animals
Het
Gas breathed-9'
Cr P* ATP* L/P
NADH/
(%)
NAD+
Transfused
63
arr
3.09
2.88
14
.12
Controls
49
arr
3.09
2.61
16
.14
Cobalt
66
arr
3.58
2.80
15
.08
Controls
55
arr
3.49
2.87
16
.09
Altitude
76
air
3.64
2.43
17
.12
Controls
54
air
3.66
2.78
17
.12
Transfused
62
4% O2
1.43
2.35
75
.16
Controls
48
4%02
1.29
2.42
72
.14
Cobalt
67
4%02
2.26
2.39
60
.11
Controls
52
4%02
1.54
2.21
66
.14
Altitude
81
4%02
1.99
2.92
46
.15
Controls
55
4% O2
1.72
2.99
51
.17
Cobalt
71
4% O2-5% CO2
3.22
2.59
22
.11
Controls
51
4% O2-5% CO2
2.29
2.17
29
.15
Altitude
77
4% O2-5% CO2
3.05
2.59
14
.14
Controls
54
4% O2-5% CO2
1.95
2.47
31
.19
* pM/gram wet tissue
The most satisfactory indication that a cell is hypoxic might be the
demonstration that it is forced to utilize anaerobic metabolism to a greater
than normal degree, even though the maintenance of normal levels of high
energy compounds is thereby accomplished. This would simplify the problem from the experimental standpoint provided a satisfactory solution of
the interpretation of "lactate increase", "lactate: pyruvate ratio" and
"excess lactate" can be achieved.
In our experiments, tests of brain function showed impairment at levels
of hypoxia which did not reduce the concentration of ATP in the brain.
Much needs to be learned about the chemical basis of brain function de-