Hemoglobin Chico [β66(E10)Lys→Thr]: A New Variant with Decreased Oxygen Affinity

Abstract

Hemoglobin Chico was discovered in an asymptomatic 3-year-old boy when a mild anemia was detected by a routine blood count. Affected individuals in three generations are also mildly anemic. The abnormal hemoglobin amounts to about 45% of the total. It separates from Hb A by cellulose acetate electrophoresis at pH 8.5 with a mobility similar to Hb J but does not separate in citrate ayar at pH 6.2. Stability in isopropanol is slightly decreased. Its structure differs from the normal by the substitution of a threonyl residue for lysyl residue at position 66(E10) of the 8 chain. The P₅₀ of the oxygen equilibrium curve of whole blood at 37°C was 38 torr compared with controls of 27±2 torr. The P₅₀ binding studies of the isolated Hb Chico revealed a unique right shift of the equilibrium curve with an oxygen binding constant (1/P₅₀) about half of normal. The remaining allosteric properties were essentially normal. This significant decrease in oxygen affinity appears to be due to changes in the heme region which result from the substitution of the normal β66 lysyl by the threonyl residue.