Mapping glycation and glycoxidation sites in collagen I of human cortical bone
Paul Voziyan,
Sasidhar Uppuganti,
Micheal Leser,
Kristie L. Rose,
Jeffry S. Nyman
Affiliations
Paul Voziyan
Department of Orthopaedic Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Vanderbilt Center for Matrix Biology, Vanderbilt University Medical Center, Nashville, TN 37212, United States; Corresponding authors at: South Tower, Suite 4200
Sasidhar Uppuganti
Department of Orthopaedic Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, United States
Micheal Leser
Department of Biochemistry and Proteomics Core, Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN 37232, United States
Kristie L. Rose
Department of Biochemistry and Proteomics Core, Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN 37232, United States
Jeffry S. Nyman
Department of Orthopaedic Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN 37212, United States; Corresponding authors at: South Tower, Suite 4200
Accumulation of advanced glycation end products (AGEs), particularly in long-lived extracellular matrix proteins, has been implicated in pathogenesis of diabetic complications and in aging. Knowledge about specific locations of AGEs and their precursors within protein primary structure is critical for understanding their physiological and pathophysiological impact. However, the information on specific AGE sites is lacking. Here, we identified sequence positions of four major AGEs, carboxymethyllysine, carboxyethyllysine, 5-hydro-5-methyl imidazolone, and 5-hydro-imidazolone, and an AGE precursor fructosyllysine within the triple helical region of collagen I from cortical bone of human femurs. The presented map provides a basis for site-specific quantitation of AGEs and other non-enzymatic post-translational modifications and identification of those sites affected by aging, diabetes, and other diseases such as osteoporosis; it can also help in guiding future studies of AGE impact on structure and function of collagen I in bone.