Clinical Chemistry, Vol 16, 945-950, Copyright © 1970 by the American Association for Clinical Chemistry

Molecular Basis for a Simple, Specific Test for S Hemoglobin: the Murayama Test

¹ Department of Pathology, Blodgett Memorial Hospital, Grand Rapids, Mich. 49506 (R.M.N., B.M.N.); Wayne State University School of Medicine, Detroit, Mich. 48207 (R.L.H.); U.S. Army Medical Research Laboratory, Ft. Knox, Ky. 40121 (F.R.C.); and Stanford University Medical Center, Stanford, Calif. 94035 (P.L.W.).

The Murayama test, a new, specific test for S hemoglobin, is based on the molecular mechanism of sickling for S hemoglobin proposed by Murayama [Clin. Chem. 14, 578 (1967)]. The test depends on a feature of molecular structure: hydrophobic bonds formed between interacting tetramers by the no. 6 valine, which is substituted for glutamic acid near the N-terminal end of each S globin chain. Existence of these particular hydrophobic bonds is manifested in deoxygenated, concentrated hemolysates by reversible sol— gel transformations at 0° and 37°C. In such systems, demonstration of reversible, temperature-dependent sol—gel transformations (a negative temperature coefficient of gelation) is specific for S hemoglobin or the S structural variant, hemoglobin C (Harlem). The test is simple, has clear endpoints, will detect both homozygous and heterozygous S hemoglobin, and is specific. A practical approach is suggested to the precise identification of S and non-S sickling hemoglobins in the diagnostic laboratory. The close agreement between Murayama’s hypothesis for sickling in S hemoglobin and our results with 29 cases of S hemoglobin and 37 controls further support his views.

Submitted on August 3, 1970