Hemoglobin M Reserve: studies on identification and characterization.

Abstract

Abstract A family with hereditary cyanosis secondary to a hemoglobin M is reported; pending completion of amino acid analysis this abnormal hemoglobin is designated hemoglobin M Reserve . The M hemoglobin was separated by electrophoretic and chromatographic techniques and comprised 30 per cent of the proband's total hemoglobin. A qualitatively abnormal A 2 hemoglobin was also demonstrated. The isolated hemoglobin M had spectral absorption abnormalities in the 480 to 520 and 600 to 680 m μ ranges when in the oxy-, deoxy-, met-, and cyanmethemoglobin states; however, prolonged reduction with dithionite eliminated the spectral abnormalities present in the deoxygenated state. The structural abnormality of the hemoglobin M molecule was located in the alpha polypeptide chain and resulted in reduced oxygen affinity and decreased reversible oxygen binding capacity. Other demonstrable abnormalities included increased resistance to nitrite-induced methemoglobin formation, increased rate of ferricyanide-induced methemoglobin formation, and an increased rate of methemoglobin formation duing hemoglobin autooxidation. There were no demonstrable abnormalities in red cell content of reduced glutathione, glutathione peroxidase, TPN-methemoglobin reductase, or DPN diaphorase to explain these changes in rates of heme iron oxidation. The behavioral abnormalities are apparently secondary to the molecular conformational changes within the hemoglobin M molecule that are consequent upon the amino acid substitution, internal bonding of the ionized radical of the abnormal amino acid with heme iron, and altered interaction between alpha and beta polypepttde chains.