1. PENTOSE PHOSPHATE CYCLE
41
C-l:C-6 ratio of incorporation decreases slightly whereas the C-l:C-6
of C0 2 increases markedly. Furthermore, Abraham et al. showed that
both the oxidation of glucose-6-phosphate and citrate in alloxan-diabetic
rat liver homogenate produced the same amount of TPNH (299). They
concluded that TPNH production is not a controlling factor for fatty
acid synthesis in these diabetic rat liver preparations. Finally, experiments with glucose-l-H
3
and lactate-2-H
3 using normal fed rat liver
indicated that the contribution of the labeled glucose to lipogenesis is
less than that of the labeled lactate (300). The conclusion is that the
oxidative pentose phosphate cycle is not a major source of TPNH for
this synthesis.
The effect of fasting on the oxidative pentose phosphate cycle activity
in the liver of normal rats has already been mentioned. In Table V are
summarized some effects of other types of dietary conditions on the liver
pentose phosphate cycle activity. A few remarks are appropriate regarding some of these effects. With the choline (fat free) deficient diet, the
rat liver shows signs of fatty degeneration. When the rat is fed this diet
for a short time, no fatty degeneration is apparent in the liver. During
this period, the G-6-P DH level rises above the normal level. After fatty
degeneration has manifested itself in the liver, this dehydrogenase level
drops below normal. Livers of rats fasted 48 hours and then refed a
high-carbohydrate, low-fat diet give a large and progressive conversion
of the C-l of glucose to C0 2 , whereas the conversion of C-6 remains
constant. The effect of a high-fructose diet is strikingly greater than
that of a high-glucose diet. In the ethionine experiment, this compound
is not uniformly effective in blocking enzyme synthesis. Aside from a
decrease in synthesis of 6-PG DH, ethionine interferes with the synthesis
of glucose-6-phosphatase, phosphoglucomutase, fructose-l,6-diphosphatase, and phosphohexose isomerase. The experiments with the scorbutogenic diet also showed that there is no change in the oxidation rate of
the C-l of glucose to C0 2 , but there is a decrease in that of C-6.
The intermediary metabolism of glucose has also been studied in the
cold-acclimatized rat (304, 305). In one case, rats were maintained at
0-2°C. for longer than 120 days. When compared with control rats
maintained at 25°C. for the same period of time, the cold acclimatized
rats have depressed hepatic lipogenesis and carbohydrate metabolism
(304). The C-l:C-6 ratios of C0 2 from glucose are not significantly
different between the controls and the experimental animals, a result
indicating that the reduced lipogenesis is not associated with the decreased glucose metabolism. Hannon and Vaughn, however, found that
when rats are exposed to the cold (5± 1°C.) for only 3-4 weeks, the
G-6-P DH and 6-PG DH levels are decreased markedly, the former to
41
C-l:C-6 ratio of incorporation decreases slightly whereas the C-l:C-6
of C0 2 increases markedly. Furthermore, Abraham et al. showed that
both the oxidation of glucose-6-phosphate and citrate in alloxan-diabetic
rat liver homogenate produced the same amount of TPNH (299). They
concluded that TPNH production is not a controlling factor for fatty
acid synthesis in these diabetic rat liver preparations. Finally, experiments with glucose-l-H
3
and lactate-2-H
3 using normal fed rat liver
indicated that the contribution of the labeled glucose to lipogenesis is
less than that of the labeled lactate (300). The conclusion is that the
oxidative pentose phosphate cycle is not a major source of TPNH for
this synthesis.
The effect of fasting on the oxidative pentose phosphate cycle activity
in the liver of normal rats has already been mentioned. In Table V are
summarized some effects of other types of dietary conditions on the liver
pentose phosphate cycle activity. A few remarks are appropriate regarding some of these effects. With the choline (fat free) deficient diet, the
rat liver shows signs of fatty degeneration. When the rat is fed this diet
for a short time, no fatty degeneration is apparent in the liver. During
this period, the G-6-P DH level rises above the normal level. After fatty
degeneration has manifested itself in the liver, this dehydrogenase level
drops below normal. Livers of rats fasted 48 hours and then refed a
high-carbohydrate, low-fat diet give a large and progressive conversion
of the C-l of glucose to C0 2 , whereas the conversion of C-6 remains
constant. The effect of a high-fructose diet is strikingly greater than
that of a high-glucose diet. In the ethionine experiment, this compound
is not uniformly effective in blocking enzyme synthesis. Aside from a
decrease in synthesis of 6-PG DH, ethionine interferes with the synthesis
of glucose-6-phosphatase, phosphoglucomutase, fructose-l,6-diphosphatase, and phosphohexose isomerase. The experiments with the scorbutogenic diet also showed that there is no change in the oxidation rate of
the C-l of glucose to C0 2 , but there is a decrease in that of C-6.
The intermediary metabolism of glucose has also been studied in the
cold-acclimatized rat (304, 305). In one case, rats were maintained at
0-2°C. for longer than 120 days. When compared with control rats
maintained at 25°C. for the same period of time, the cold acclimatized
rats have depressed hepatic lipogenesis and carbohydrate metabolism
(304). The C-l:C-6 ratios of C0 2 from glucose are not significantly
different between the controls and the experimental animals, a result
indicating that the reduced lipogenesis is not associated with the decreased glucose metabolism. Hannon and Vaughn, however, found that
when rats are exposed to the cold (5± 1°C.) for only 3-4 weeks, the
G-6-P DH and 6-PG DH levels are decreased markedly, the former to