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Science 9 February 1973:
Vol. 179. no. 4073, pp. 532 - 537
DOI: 10.1126/science.179.4073.532
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Articles

Hemolytic Anemia and G6PD Deficiency

Physiologic activity, not in vitro activity, of enzymes is related to the severity of genetic diseases

Akira Yoshida 1

1 Department of biochemical genetics, City of Hope National Medical Center, Duarte, California 91010

The severity of enzyme deficiency often does not correlate well with the clinical severity of genetic diseases. Thus, some G6PD variants associated with severe enzyme deficiency, such as Union and Markham, cause no hemolytic problem, while some variants associated with less severe deficiency, such as Manchester, Alhambra, and Tripler, cause chronic hemolytic anemia. The kinetic characteristics of these variant enzymes have not explained the discrepancy. However, examination of the normal and variant enzymes under simulated physiologic conditions, with the effects of various intermediate metabolites and co-enzymes in red cells being taken into consideration, reveal that the G6PD's from hemolytic variant subjects are strongly inhibited by a physiologic concentration of NADPH because of their high Michaelis constant for NADP or low inhibition constant for NADPH, and they are more sensitive to inhibition by ATP. These variant enzymes cannot generate enough NADPH in red cells to maintain an adequate concentration of reduced glutathione. The nonhemolytic variant enzymes are far less sensitive to the inhibition by NADPH because of their low Michaelis constant for NADP and high inhibition constant for NADPH. The physiologic activity of these nonhemolytic variant enzymes is estimated to be more than 30 percent of the activity of the normal G6PD, and this activity is adequate to maintain the red cells unhemolyzed.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Sickle Cell Trait and Glucose-6-Phosphate Dehydrogenase Deficiency: Effects on Health and Military Performance in Black Navy Enlistees.
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Arch Intern Med 141, 1485-1488
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Glucose-6-phosphate deficiency and inhibition by NADPH: a self-contradictory argument.
H. Kirkman and G. Gaetani (1975)
Science 190, 171-172
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Enzyme Polymorphism and Metabolism.
G. B. Johnson (1974)
Science 184, 28-37
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Glucose-6-Phosphate Dehydrogenase Deficiency in Military Recruits.
D. E. Uddin, L. G. Dickson, and C. E. Brodine (1974)
JAMA 227, 1408-1409
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