The discovery of glycated hemoglobin: a major event in the study of nonenzymatic chemistry in biological systems.
Glycated hemoglobins are minor components of human hemoglobin (Hb). These are formed nonenzymatically by condensation of glucose or other reducing sugars with alpha- and beta-chains of hemoglobin A. The subfraction HbA1c, a nonenzymatic glycation at the amino-terminal valines of the beta-chain, was identified by the author in the 1960s as a minor "abnormal fast-moving hemoglobin band" in diabetic patients during routine screening for hemoglobin variants. This finding later turned out to be an important biomolecular marker with clinical and pathological applications. Measurement of HbA1c in diabetic patients is an established procedure for evaluating long-term control of diabetes, and the introduction of this measurement represents an outstanding contribution to the quality of care of diabetic patients in this century. More importantly, HbA1c is the first example of in vivo nonenzymatic glycation of proteins, and its discovery opened new and still-growing avenues of research on Maillard reactions in biological systems, including the concept of advanced glycation/lipoxidation end products (AGEs/ALEs) and the development of diabetic complications and various diseases associated with aging. Although interest in the Maillard reaction is growing rapidly, much remains to be done in this field, including detection and characterization of all in vivo AGEs/ALEs, development and clinical applications of AGE inhibitors and breakers, as well as investigations into the possible roles of the Maillard reaction in regulatory biology and carcinogenesis.
Rahbar
Samuel
S
City of Hope National Medical Center and Beckman Research Institute, 1500 E. Duarte Road, Duarte, CA 91010, USA. srahbar@coh.org
D001671:Biochemistry / Q000266:history; D003920:Diabetes Mellitus / Q000097:blood / Q000453:epidemiology; D006442:Glycated Hemoglobin / Q000266:history*; D049673:History, 20th Century; D006801:Humans; D015995:Prevalence
D006442:Glycated Hemoglobin