title: Glycerated hemoglobin alpha 2 beta 2(82) (EF6) N-epsilon-glyceryllysine: a new post-translational modification occurring in erythrocyte bisphosphoglyceromutase deficiency.
abstract: A new minor Hb fraction initially designated Hbx, has been found in the hemolysate of a erythremic patient that we have previously described with a complete erythrocyte bisphosphoglyceromutase (BPGM) (E.C.2.7.5.4.) deficiency. Hbx (3.5% of the total) was detected by isoelectric focusing (IEF) and exhibited electrophoretic and chromatographic properties similar to that of several variants of the Hb central cavity. By density fractionation of red cells, it was demonstrated that Hbx was an aging hemoglobin as in the case of glycated Hb A1c. Functional studies revealed a low oxygen affinity and almost complete inhibition of the allosteric effect of the organic phosphate effectors. Structural studies demonstrated an absence of tryptic cleavage between the peptides beta T9 and beta T10 suggesting the presence of an adduct on Lys beta 82 or on a neighboring residue. FAB mass spectrometry, CID/MIKE spectra and a specific enzymatic assay with glyoxylate reductase, demonstrated that the 82 adduct was a glycerate moiety. It was concluded that Hbx was a glycerylated Hb: alpha 2 A beta 2(82) (EF6) N-epsilon-glyceryllysine, to our knowledge the first example of glycerylated protein. The mechanism of formation of glyceryl-Hb, which was found in the four studied subjects with a BPGM deficiency, remains to be determined.
mesh_terms: D001731:Bisphosphoglycerate Mutase / Q000172:deficiency*; D004905:Erythrocyte Aging; D004912:Erythrocytes / Q000378:metabolism*; D006455:Hemoglobins, Abnormal / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D013058:Mass Spectrometry; D010770:Phosphotransferases / Q000172:deficiency*; D011499:Protein Processing, Post-Translational
chemical_list: D006455:Hemoglobins, Abnormal; C048900:hemoglobin, glycerated; D010770:Phosphotransferases; D001731:Bisphosphoglycerate Mutase