Summary
The activities of NADH- and NADPH-dependent methemoglobin reductases were investigated in 22 fetuses between the 12th and 24th week of pregnancy and in eight age groups including premature and newborn babies and adults. Each blood sample was assayed simultaneously for both activities. NADH-methemoglobin reductase (MR) appears to be diminished in erythrocytes of premature and newborn babies. Infants below the 6th week of life also show significantly lower values than those observed in adults. Between 7 weeks and 6 months of life NADH-MR activity reaches values comparable to those of the adults. — NADPH activity in the erythrocytes of premature babies, newborns and infants is significantly higher than in older children and adults. Prior to the 18th week of gestation fetuses show NADH-MR levels lower than the older ones. NADH-MR values in fetuses between the 18th and 24th week of gestation are not different from those measured in premature babies. The NADPH-MR activity also appears to be significantly lower in fetuses of less than 19 weeks of intrauterine life in comparison with the older ones. Moreover, NADPH-MR activity in fetuses between the 19th and 24th week is lower than in prematures and newborns.
The possibility that low NADH-MR values in fetuses (30% as compared to adults) in the first 5 months of pregnancy could predispose to intrauterine methemoglobinemia has to be carefully evaluated when toxic drugs are prescribed to the mother.—Moreover, the still lower NADH-MR levels that might be expected in fetuses homozygous or heterozygous for NADH-MR deficiency may be a cause for the frequent occurrence of mental retardation in families with hereditary methemoglobinemia.
Zusammenfassung
Die Enzymaktivitäten der NADH-und NADPH-abhängigen Methaemoglobinreductasen wurden in 22 Feten der 12.–24. Schwangerschaftswoche und in 8 weiteren Altersgruppen von Frühgeborenen bis zu Erwachsenen bestimmt. In jeder Blutprobe wurden beide Enzyme gemessen.
Die NADH-Methaemoglobinreductase (MR) ist bei Früh-und Reifgeborenen vermindert und erreicht erst zwischen dem 2.–6. Lebensmonat die Erwachsenenwerte.
Die NADPH-Methaemoglobinreductase hat in den Erythrocyten der Früh- und Reifgeborenen und Kleinkinder signifikant höhere Aktivitäten als in den späteren Lebensaltern.
Junge Feten vor der 18. Schwangerschaftswoche haben niedrigere NADH-MR-Aktivitäten als die älteren, deren Werte mit denen der Frühgeborenen übereinstimmen.
Das gleiche Verhalten bei den jungen Feten zeigt die NADPH-MR, bei der auch die älteren Feten noch geringere Aktivitäten als Früh- und Reifgeborene haben.
Die niedrigen NADH-MR-Aktivitäten in den ersten 5 Schwangerschaftsmonaten (30% der Erwachsenenwerte) könnten bei den Feten zu einer intrauterinen toxischen Methämoglobinämie führen, wenn der Mutter Medikamente verabfolgt werden, von denen bekannt ist, daß sie eine Methämoglobinämie hervorrufen können. Noch geringere Enzymaktivitäten können bei den für einen NADH-MR-Mangel hetero- oder homozygoten Feten erwartet werden. Hierin könnte eine Ursache für das häufigere Vorkommen von geistiger Schädigung bei Familien mit erblicher Methämoglobinämie liegen.
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References
Baikie, A. G., Valtis, D. J.: Gas transport function of the blood in congenital familial methemoglobinemia. Brit. med. J.1954 II, 73.
Bartos, H. R., Desforges, J. F., Clark, N.: Erythrocyte DPNH dependent diaphorase levels in infants. Pediatrics37, 991 (1966).
Betke, K., Rau, H.: Zur Frage der Neigung junger Säuglinge an Methämoglobinämien zu erkranken. Arch. Kinderheilk.145, 195 (1952).
—— Kleihauer, E., Gärtner, Ch., Schiebe, G.: Verminderung von Methämoglobinreduktion, Diaphoraseaktivität und Flavinen in Erythrozyten junger Säuglinge. Arch. Kinderheilk.170, 66 (1964).
Bloom, G. E., Zarkowsky, H. S.: Molecular heterogencity in congenital methemoglobinemia (Abstract). Pediat. Res.3, 369 (1969).
Bodansky, O.: Methemoglobinemia and methemoglobin-producing compounds. Pharmacol. Rev.3, 144 (1951).
Brewer, G., I., Tarlov, A. R., Alving, A. S.: Methemoglobin reduction test: new, simple, in vitro test for identifying primaquine sensitivity. Bull. Wld Hlth Org.22, 633 (1960).
Brewer, J. G., Tarlov, A. R., Alving, A. S.: The methemoglobin reduction test for primaquine-type sensitivity of erythrocytes. J. Amer. med. Ass.180, 386 (1962).
Comly, H. H.: Cyanosis in infants caused by nitrates in well water. J. Amer. med. Ass.129, 112 (1945).
Cornblath, M., Hartmann, A. F.: Methemoglobinemia in infants, J. Pediat.33, 421 (1948).
Cunningham, A. A.: Resorcin poisoning. Arch. Dis. Childh.31, 173 (1956).
Darling, R. C., Roughton, F. J. W.: The effect of methemoglobin on the equilibrium between oxygen and hemoglobin. Amer. J. Physiol.137, 56 (1942).
Dieckmann, W. J.: Methemoglobinemia. Arch. intern. Med.50, 574 (1932).
Dollinger, A.: Über perorale Vergiftung durch Nitrobenzol bzw. Anilin bei Neugeborenen. Mschr. Kinderhcilk.97, 91 (1949).
Drabkin, D. L.: A simplified technique for a large scale crystallization of human oxyhemoglobin. Isomorphous transformation of hemoglobin and myoglobin in the erystalline state. Arch. Biochem.21, 224 (1949).
Evelyn, K. A., Malloy, H. T.: Microdetermination of oxyhemoglobin, methemoglobin, and sulphemoglobin in a single sample of blood. J. biol. Chem.126, 665 (1938).
Faucett, R. L., Miller, H. C.: Methemoglobinemia occurring in infants fed milk diluted with well water of high nitrate content. J. Pediat.29, 593 (1946).
Ferrant, M.: Methemoglobinemia, two cases in newborn infants caused by nitrates in well water. J. Pediat.29, 585 (1946).
Fialkow, Ph. J., Browder, J. A., Sparkes, R. S., Motulsky, A. G.: Mental retardation in methemoglobinemia due to diaphorase deficiency. New Engl. J. Med.273, 840 (1965).
Frick, P. G., Bachmann, F., Schmid, J. R.: Einc Familie mit congenitaler Methämoglobinämie infolge Diaphorasemangels. Acta haemat. (Basel)34, 215 (1965).
Gibson, Q. H., Harrison, D. C.: Familial idiopathic methemoglobinemia. Five cases in one family. Lancet1947 II, 941.
Golobuff, N., MacFayden, D. J.: Methemoglobinemia in an infant associated with application of tarbenzocaine ointment. J. Pediat.47, 222 (1955).
—— Methemoglobinemia due to benzocaine. Pediatrics21, 340 (1958).
Grauberth, J., Bloom, C. J., Coleman, F. C., Solomon, H. N.: Dye poisoning in the nursery. A review of seventeen cases. J. Amer. med. Ass.128, 1155 (1945).
Hegesh, E., Avron, M.: The enzymatic reduction of ferrihemoglobin II. Purification of a ferrihemoglobin reductase from human erythrocytes. Biochim. biophys. Acta (Amst.)146, 397 (1967).
—— Calmanovici, N., Avron, M.: New method for determining ferrihemoglobin reductase (NADH-methemoglobin reductase) in erythrocytes. J. Lab. clin. Med.72, 339 (1968).
Hennessey, A. W., Waltersdorph, A. M., Huennekens, F. M., Gabrio, B. W.: Erythrocyte metabolism. VI separation of erythrocyte enzymes from hemoglobin. J. clin. Invest.41, 1257 (1962).
Hörlein, H., Weber, G.: Über chronische familiäre Methämoglobinämie und eine neue Modifikation des Methämoglobins. Dtsch. med. Wschr.73, 476 (1948).
Howart, B. E.: Epidemic of aniline methaemoglobinaemia in newborn infants. Lancet1951 I, 934.
Huennekens, F. M., Caffrey, R. W., Basford, R. E., Gabrio, B. W.: Erythrocyte metabolism IV. Isolation and properties of methemoglobin reductase. J. biol. Chem.79, 65 (1957).
—— Kerwar, G. K., Kajita, A.: Methemoglobin reductases In: E. Beutler, Hereditary disorders of erythrocyte metabolism, p. 87. New York and London: Grune & Stratton 1968.
Jaffé, E. R., Neumann, G., Rothberg, H., Wilson, F. T., Webster, R. M., Wolff, J. A.: Hereditary methemoglobinemia with and without mental retardation. Amer. J. Med.41, 42 (1966).
—— Hereditary methemoglobinemias associated with abnormalities in the metabolism of erythrocytes. Amer. J. Med.41, 786 (1966).
Kaplan, J. C., Beutler, E.: Elektrophoresis of red cell NADH- and NADPH-diaphorases in normal subjects and patients with congenital methemoglobinemia. Biochem. biophys., Res. Commun.29, 605 (1967).
Kiese, M., Schneider, C., Waller, H. D.: Hämoglobinreduktase. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak.231, 158 (1957).
Lonn, L., Motulsky, A. G.: Electrophoretic demonstration of a nonhemoglobin protein (methemoglobin reductase) in hemolysates. Clin. Res. Proc.5, 157 (1957).
McDonald, C. D., Huisman, T. H. J.: A comparative study of enzymic activities in normal adult and cord blood erythrocytes as related to the reduction of methemoglobin. Clin. chim. Acta7, 555 (1962).
Miller, D. R., Kotok, D.: The micro-methemoglobin reduction screening test for G-6-PD deficiency in childhood. Pediatrics41, 528 (1968).
Motulsky, A.: Methemoglobin reductase system. In Disturbances of cellular metabolism, Report of the 32nd Ross conference on pediatric research, Columbus, Ohio, Ross Laboratories (1959), p. 55.
Oski, F. A., Naiman, J. L.: Hematologic problems in the newborn, p. 131. Philadelphia and London: Saunders Co. 1966.
Patten, B. M.: Human embriology, p. 186. Toronto: Blakiston Co. 1948.
Pepper, G., Weinstein, H. G., Hcller, P.: Congenital methemoglobinemia in pregnancy. J. Amer. med. Ass.177, 328 (1961).
Peterson, H. C. de: Acquired methemoglobinemia in an infant due to benzocaine suppository. New Engl. J. Med.263, 454 (1960).
Rodeck, H., Westhaus, H.: Die Anilinvergiftung durch Wäschetinten und Stempelfarben bei Säuglingen. Ein Bericht an Hand einer Gruppenvergiftung von 41 Säuglingen. Arch. Kinderheilk.145, 77 (1952).
Roe, H. E.: Methemoglobinemia following the administration of bismuth subnitrates. J. Amer. med. Ass.101, 352 (1933).
Ross, J. D.: Deticient activity of DPNH dependent methemoglobin diaphorase in cord blood erythrocytes. Blood21, 51 (1963).
Sass, M. D., Caruso, C. J., Farhangi, M.: TPNH-methemoglobin reductase deficiency: A new red cell enzyme defect. J. Lab. clin. Med.70, 760 (1967).
Schumacher, P.: Nil nocere! Akute Phenacetinvergiftung beim jungen Säugling. Münch. med. Wschr.25, 1083 (1959).
Singer, K.: Hereditary hemolytic disorders associated with abnormal hemoglobins. Amer. J. Med.18, 633 (1955).
Scott, E. M., Duncan, I. W., Ekstrand, V.: The reduced pyridine nucleotide dehydrogenases of human erythrocytes. J. biol. Chim.240, 481 (1964).
—— The relation of diaphorase of human erythrocytes to inheritance of methemoglobinemia. J. clin. Invest.39, 1176 (1960).
Griffith, I. V.: The enzymic defect of hereditary methemoglobinemia: diaphorase. Biochim. biophys. Acta (Amst.)34, 584 (1959).
Scott, E. P., Prince, G. E., Rotondo, C. C.: Dye poisoning in infancy. J. Pediat.28, 713 (1946).
Tönz, O.: The congenital methemoglobinemias. Basel-New York: S. Karger 1968.
Vetrella, M., neuvians, D., Barthclmai, W.: An improved method for determining NADPH-methemoglobin reductase in erythrocytes (to be published).
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Vetrella, M., Åstedt, B., Barthelmai, W. et al. Activity of NADH- and NADPH-dependent methemoglobin reductases in erythrocytes from fetal to adult age. Klin Wochenschr 49, 972–977 (1971). https://doi.org/10.1007/BF01489462
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DOI: https://doi.org/10.1007/BF01489462
Key-words
- NADH- and NADPH-dependent methemoglobin reductases
- fetus
- postnatal life
- mental retardation
- hereditary methemoglobinemia