The occurrence of a novel hydrophilic hydroperoxide, 3-hydroxy-5-hydroperoxy-2-methyl-5,6-dihydropyran-4-one, as a reactive glycation product in human plasma.
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| Abstract |
This study describes the occurrence of 3-hydroxy-5-hydroperoxy-2-methyl-5,6-dihydropyran-4-one (HMDP) in plasma obtained from normal subjects and patients with type 2 diabetes. We have shown previously that HMDP is a novel hydrophilic hydroperoxide formed in the in vitro Maillard reaction that could be analyzed using ultrasensitive chemiluminescence detection-high-performance liquid chromatography (CL-HPLC). The HMDP concentration was 273+/-227 nmol/l in normal subjects and 656+/-535 nmol/l in patients with diabetes. The HMDP concentration was proportional to the plasma glucose concentration level (r=0.640; P<0.01) but not with the glycated hemoglobin level. To investigate the in vivo effects of HMDP, a range of concentrations of the compound was incubated for different time periods with human serum albumin and lipoproteins. HMDP was found to induce denaturation of these macromolecules by modifying lysine residues and causing cross-linking and polymerization of proteins. In the presence of metal ions such as iron and copper, HMDP induced peroxidative degradation of lipoprotein lipids as measured by an elevation in thiobarbituric acid reactive substances (TBARS) concentration. These results suggested that HMDP is produced as a consequence of both hyperglycemia and increased oxidative stress, and may have the potential to contribute to the pathogenesis of arterial complications in diabetes mellitus.
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| Authors | Sittiwat Lertsiri, Jeong-Ho Oak, Kiyotaka Nakagawa, Teruo Miyazawa |
| Journal | Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1573 Issue 1 Pg. 48-54 (Oct 10 2002) ISSN: 0006-3002 [Print] Netherlands |
| PMID | 12383941 (Publication Type: Journal Article) |
| Chemical References |
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