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Research Article Free access | 10.1172/JCI106957

Unstable variant of NADH methemoglobin reductase in puerto ricans with hereditary methemoglobinemia

Joel M. Schwartz, Philip S. Paress, Jonathan M. Ross, Frank DiPillo, and Rafael Rizek

Department of Medicine at the State University of New York Downstate Medical Center, Brooklyn, New York

Department of Medicine, Coney Island Hospital affiliated with Maimonides Medical Center, Brooklyn, New York

Department of Medicine, Long Island College Hospital, Brooklyn, New York

Department of Medicine, Municipal Hospital, San Juan, Puerto Rico

Find articles by Schwartz, J. in: PubMed | Google Scholar

Department of Medicine at the State University of New York Downstate Medical Center, Brooklyn, New York

Department of Medicine, Coney Island Hospital affiliated with Maimonides Medical Center, Brooklyn, New York

Department of Medicine, Long Island College Hospital, Brooklyn, New York

Department of Medicine, Municipal Hospital, San Juan, Puerto Rico

Find articles by Paress, P. in: PubMed | Google Scholar

Department of Medicine at the State University of New York Downstate Medical Center, Brooklyn, New York

Department of Medicine, Coney Island Hospital affiliated with Maimonides Medical Center, Brooklyn, New York

Department of Medicine, Long Island College Hospital, Brooklyn, New York

Department of Medicine, Municipal Hospital, San Juan, Puerto Rico

Find articles by Ross, J. in: PubMed | Google Scholar

Department of Medicine at the State University of New York Downstate Medical Center, Brooklyn, New York

Department of Medicine, Coney Island Hospital affiliated with Maimonides Medical Center, Brooklyn, New York

Department of Medicine, Long Island College Hospital, Brooklyn, New York

Department of Medicine, Municipal Hospital, San Juan, Puerto Rico

Find articles by DiPillo, F. in: PubMed | Google Scholar

Department of Medicine at the State University of New York Downstate Medical Center, Brooklyn, New York

Department of Medicine, Coney Island Hospital affiliated with Maimonides Medical Center, Brooklyn, New York

Department of Medicine, Long Island College Hospital, Brooklyn, New York

Department of Medicine, Municipal Hospital, San Juan, Puerto Rico

Find articles by Rizek, R. in: PubMed | Google Scholar

Published June 1, 1972 - More info

Published in Volume 51, Issue 6 on June 1, 1972
J Clin Invest. 1972;51(6):1594–1601. https://doi.org/10.1172/JCI106957.
© 1972 The American Society for Clinical Investigation
Published June 1, 1972 - Version history
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Abstract

The electrophoretic mobility of erythrocyte NADH methemoglobin reductase in five hereditary methemoglobinemia patients from three Puerto Rican kindreds was 118% of normal at pH 8.6. The methemoglobin ferrocyanide reductase activity of the enzyme in erythrocyte hemolysates was 3.2-6.4% of normal. Electrophoresis of hemolysates prepared from the blood of patients from two different families at six pH values between 4.6 and 9.3 did not differentiate between the variant enzymes. Examination of the deficient enzymes extracted from the erythrocytes of one patient from each kindred revealed altered affinity for NADH and dichloroindophenol dye and decreased thermal stability. The quantitative similarity of the abnormal findings, together with the Puerto Rican origin of the kindreds, suggested that the cyanotic patients possessed the same abnormal enzyme and were thus homozygous for the same rare mutant gene. Consanguinity of the kindreds could not be established.

The rates of decline of the normal and variant NADH methemoglobin reductase enzymes in vivo were measured in erythrocyte fractions of increasing cell age. The rate of decline of the variant enzyme was increased 20-fold by comparison with the normal enzyme. The methemoglobin percentage in erythrocyte fractions of increasing cell age correlated inversely with the activity of the variant. The variant enzyme averaged 37% of normal mean activity in young cells and 1% in old cells. The normal enzyme, on the other hand, lost only one-sixth of its activity as the cells aged, and the methemoglobin content in old normal cells did not rise. These observations support the hypothesis that the deficient activity and the heterogeneous pattern of methemoglobin accumulation in vivo arise principally from the accelerated inactivation of variant NADH methemoglobin reductase during the life-span of the red blood cell.

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