30
Ν. G. PON
and congenital hemolytic anemias, blood loss, pernicious anemia, sprue,
and neoplastic diseases results in higher than normal activities of both
dehydrogenases (205), although purine nucleoside Phosphorylase activity remains the same. Full-term infants also show a higher level of
glucose-6-phosphate dehydrogenase in the umbilical cord blood than
do premature infants (218). The latter are frequently susceptible to
anemic tendencies. Since glutathione and stability of glutathione are
not significantly different in cord blood of full-term babies and of premature babies, conclusions could not be made as to what factors are
responsible for shortening the life span of the erythrocytes in premature
infants. Perhaps both rapid destruction of red blood cells and poor
erythropoiesis in the bone marrow occur.
One of the most intensive phases of study on glucose-6-phosphate
dehydrogenase (G-6-P DH) is the hemolytic anemia resulting from a
lack or deficiency of this enzyme. Bruns and Werners (213) state that,
in a United Fruit Company Annual Report in 1926, W. Cordes
described the discovery of cases of hemolysis in Negroes who were
given pamaquine for treatment of malaria. Since then much research
has been carried out to determine the mechanism of this type of
hemolysis. The facts can be outlined as follows:
Certain exogenous agents, when ingested, cause acute hemolytic
anemia in subjects who have a deficiency in reduced glutathione (GSH)
and G-6-P DH in the red blood cells. Some of these agents are pamaquine
(219), primaquine (219), nitrofurantoin (220), naphthalene (220), aniline derivatives (219), and Vicia faba beans (220, 221). The hemolysis
appears to be associated with the GSH level, the latter being needed,
somehow, for maintaining the integrity of the erythrocytes (222). GSH
is linked to G-6-P DH through TPN
+ , the latter becoming TPNH while
glucose-6-phosphate is being oxidized. In turn, TPNH reacts with oxidized glutathione (GSSG) catalyzed by glutathione reductase, to yield
GSH, thereby regenerating TPN
+ . Although primaquine-sensitive individuals have a deficiency in the blood G-6-P DH level, glutathione
reductase activity of their hemolyzates is increased, as if to compensate
partially for the deficiency of the former enzyme (223). Nevertheless,
GSH level in erythrocytes of primaquin-sensitive subjects is decreased
(222). The critical factor thus seems to be the level of TPNH. Old
erythrocytes are hemolyzed by the drug, but after this first attack there
is a period of several weeks during which more primaquine has no
further effect (224). The younger red blood cell population, however,
contains higher G-6-P DH activity than the old cells, although not normal. Therefore the younger cells are able to maintain a high enough
level of reduced glutathione to protect the cells.
Ν. G. PON
and congenital hemolytic anemias, blood loss, pernicious anemia, sprue,
and neoplastic diseases results in higher than normal activities of both
dehydrogenases (205), although purine nucleoside Phosphorylase activity remains the same. Full-term infants also show a higher level of
glucose-6-phosphate dehydrogenase in the umbilical cord blood than
do premature infants (218). The latter are frequently susceptible to
anemic tendencies. Since glutathione and stability of glutathione are
not significantly different in cord blood of full-term babies and of premature babies, conclusions could not be made as to what factors are
responsible for shortening the life span of the erythrocytes in premature
infants. Perhaps both rapid destruction of red blood cells and poor
erythropoiesis in the bone marrow occur.
One of the most intensive phases of study on glucose-6-phosphate
dehydrogenase (G-6-P DH) is the hemolytic anemia resulting from a
lack or deficiency of this enzyme. Bruns and Werners (213) state that,
in a United Fruit Company Annual Report in 1926, W. Cordes
described the discovery of cases of hemolysis in Negroes who were
given pamaquine for treatment of malaria. Since then much research
has been carried out to determine the mechanism of this type of
hemolysis. The facts can be outlined as follows:
Certain exogenous agents, when ingested, cause acute hemolytic
anemia in subjects who have a deficiency in reduced glutathione (GSH)
and G-6-P DH in the red blood cells. Some of these agents are pamaquine
(219), primaquine (219), nitrofurantoin (220), naphthalene (220), aniline derivatives (219), and Vicia faba beans (220, 221). The hemolysis
appears to be associated with the GSH level, the latter being needed,
somehow, for maintaining the integrity of the erythrocytes (222). GSH
is linked to G-6-P DH through TPN
+ , the latter becoming TPNH while
glucose-6-phosphate is being oxidized. In turn, TPNH reacts with oxidized glutathione (GSSG) catalyzed by glutathione reductase, to yield
GSH, thereby regenerating TPN
+ . Although primaquine-sensitive individuals have a deficiency in the blood G-6-P DH level, glutathione
reductase activity of their hemolyzates is increased, as if to compensate
partially for the deficiency of the former enzyme (223). Nevertheless,
GSH level in erythrocytes of primaquin-sensitive subjects is decreased
(222). The critical factor thus seems to be the level of TPNH. Old
erythrocytes are hemolyzed by the drug, but after this first attack there
is a period of several weeks during which more primaquine has no
further effect (224). The younger red blood cell population, however,
contains higher G-6-P DH activity than the old cells, although not normal. Therefore the younger cells are able to maintain a high enough
level of reduced glutathione to protect the cells.