title: Aldimine Formation Reaction, the First Step of the Maillard Early-phase Reaction, Might be Enhanced in Variant Hemoglobin, Hb Himeji.
abstract: Hb Himeji (β140Ala→Asp) is known as a variant hemoglobin in which glycation is enhanced and HbA1c measured by immunoassay shows a high value. The phenomenon of enhanced glycation in Hb Himeji is based on the fact that the glycation product of variant hemoglobin (HbX1c) shows a higher value than HbA1c. In this study, we investigated whether aldimine formation reaction, the first step of the Maillard early-phase reaction, is enhanced in Hb Himeji in vitro. Three non-diabetic subjects with Hb Himeji and four non-diabetic subjects without variant hemoglobin were enrolled. In order to examine aldimine formation reaction, whole blood cells were incubated with 500 mg/dl of glucose at 37°C for 1 hour and were analyzed by high-performance liquid chromatography. Both HbA1c and HbX1c were not increased in this condition. After incubation with glucose, labile HbA1c (LA1c) fraction increased in the controls (1.1±0.3%). In subjects with Hb Himeji increases in the labile HbX1c (LX1c) fraction as well as the LA1c fraction were observed, and the degree of increase in the LX1c fraction was significantly higher than that of the LA1c fraction (1.8±0.1% vs. 0.5±0.2%, P<0.01). We have shown for the first time that aldimine (LX1c) formation reaction might be enhanced in Hb Himeji in vitro. The 140th amino acid in β chain of hemoglobin is suggested to be involved in aldimine formation reaction.
authors.affiliation: Department of Internal Medicine, Kawanishi City Hospital, Kawanishi, Japan m-koga@kawanishi-city-hospital.com.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Koga
authors.affiliation: Department of Internal Medicine, Kawanishi City Hospital, Kawanishi, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Inada
authors.affiliation: Department of Diabetes and Metabolism, Osaka General Medical Center, Osaka, Japan.
authors.forename: Sayoko
authors.initials: S
authors.lastname: Shimizu
authors.affiliation: Department of Diabetes and Metabolism, Osaka General Medical Center, Osaka, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hatazaki
authors.affiliation: Department of Diabetes and Metabolism, Osaka General Medical Center, Osaka, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Umayahara
authors.affiliation: Department of Internal Medicine, Kuma Hospital, Kobe, Japan.
authors.forename: Eijun
authors.initials: E
authors.lastname: Nishihara
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D003920:Diabetes Mellitus / Q000097:blood; D005260:Female; D005947:Glucose / Q000737:chemistry; D006442:Glycated Hemoglobin / Q000737:chemistry; D017127:Glycation End Products, Advanced / Q000097:blood* / Q000737:chemistry; D006455:Hemoglobins, Abnormal / Q000032:analysis / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D015416:Maillard Reaction; D008297:Male; D008875:Middle Aged; D009154:Mutation
chemical_list: D005947:Glucose; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D006455:Hemoglobins, Abnormal; C517652:hemoglobin A1c protein, human; C048296:hemoglobin Himeji
keywords: Hb Himeji; HbA1c; Maillard reaction; glycation; variant hemoglobin