Degradation of 1-Deoxy-<scp>d</scp>-<i>erythro</i>-hexo-2,3-diulose in the Presence of Lysine Leads to Formation of Carboxylic Acid Amides

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Background: Advanced glycation end products (AGEs) play a prominent role in various pathophysiologies. Results: A new class of lysine amide modifications was established in vivo. Conclusion: Non-enzymatic Maillard mechanisms participate on amide-AGE formation pathways in vivo. Significance: Plasma levels of the amide-AGEs were in the same range similar to other established lysine modifications and suggest a comparable impact of non-enzymatic biochemistry on pathophysiologies in the human organism.

Section: -Glycoloyl Lysine Have Been Established For the Reaction Of mentioning

confidence: 69%

Section: Amide-ages In Human Blood Plasma Of Uremic Patients Versus Hmentioning

confidence: 80%

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Molecular Basis of Maillard Amide-Advanced Glycation End Product (AGE) Formation in Vivo

Henning¹,

Smuda²,

Girndt

et al. 2011

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“…Hence, 1-DG is by far the most reactive and thus important ␣-DC intermediate regarding glucose-derived AGEs. In particular, amine-induced ␤-cleavage in the presence of lysine leads directly to carboxylic acid amides, a novel class of amide-AGEs (14,62) that are of quantitative importance in vivo (9).…”

Section: Discussionmentioning

confidence: 99%

Extending the Spectrum of α-Dicarbonyl Compounds in Vivo

Henning¹,

Liehr²,

Girndt

et al. 2014

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114

Background: ␣-Dicarbonyls are central intermediates in the formation of advanced glycation end products (AGEs). Results: A quantitation method for the complete spectrum relevant in vivo was established. Conclusion: Non-enzymatic chemistry of glucose and L-ascorbic acid as precursors and ␣-dicarbonyl intermediates play an important role in vivo. Significance: Knowledge of plasma levels of ␣-dicarbonyls is crucial to understand the complex pathways of AGE formation in vivo.

“…Degradation of glucose-derived Amadori products, for example, yields 1-deoxyglucosone (7,19) and its tautomers, which upon nucleophilic attack by a N ⑀ -amino group of a lysine residue undergo hydrolytic ␤-cleavage yielding amide-AGEs, such as N ⑀ -acetyl-, formyl-, and glycerinyl-lysine ( Fig. 1) (20). Generally, AGEs can alter the structure of proteins contributing to diabetic retinopathy (21,22), increased arterial stiffness (23,24), or impaired renal function (25) along with aging and diabetes.…”

mentioning

confidence: 99%

Plasma Proteins Modified by Advanced Glycation End Products (AGEs) Reveal Site-specific Susceptibilities to Glycemic Control in Patients with Type 2 Diabetes

Greifenhagen

Frolov

Blüher

et al. 2016

Protein glycation refers to the reversible reaction between aldoses (or ketoses) and amino groups yielding relatively stable Amadori (or Heyns) products. Consecutive oxidative cleavage reactions of these products or the reaction of amino groups with other reactive substances (e.g. ␣-dicarbonyls) yield advanced glycation end products (AGEs) that can alter the structures and functions of proteins. AGEs have been identified in all organisms, and their contents appear to rise with some diseases, such as diabetes and obesity. Here, we report a pilot study using highly sensitive and specific proteomics approach to identify and quantify AGE modification sites in plasma proteins by reversed phase HPLC mass spectrometry in tryptic plasma digests. In total, 19 AGE modification sites corresponding to 11 proteins were identified in patients with type 2 diabetes mellitus under poor glycemic control. The modification degrees of 15 modification sites did not differ among cohorts of normoglycemic lean or obese and type 2 diabetes mellitus patients under good and poor glycemic control. The contents of two amide-AGEs in human serum albumin and apolipoprotein A-II were significantly higher in patients with poor glycemic control, although the plasma levels of both proteins were similar among all plasma samples. These two modification sites might be useful to predict long term, AGE-related complications in diabetic patients, such as impaired vision, increased arterial stiffness, or decreased kidney function.The reaction between reducing sugars (i.e. aldoses or ketoses) and amines is termed glycation or nonenzymatic glycosylation (1). The initially formed aldimines or ketimines can rearrange forming relatively stable Amadori or Heyns products, respectively. Consecutive rearrangements and oxidations yield advanced glycation end products (AGEs) 3 (2-6), a structurally heterogeneous group of compounds including cross-linked proteins (1). Alternatively, ␣-dicarbonyls generated by Amadori degradation (7,8), saccharide autoxidation (9, 10), lipid peroxidation (11, 12), and enzymatic reactions (13-15) can modify the side chains of lysine and arginine residues (16 -18). Degradation of glucose-derived Amadori products, for example, yields 1-deoxyglucosone (7, 19) and its tautomers, which upon nucleophilic attack by a N ⑀ -amino group of a lysine residue undergo hydrolytic ␤-cleavage yielding amide-AGEs, such as N ⑀ -acetyl-, formyl-, and glycerinyl-lysine ( Fig. 1) (20). Generally, AGEs can alter the structure of proteins contributing to diabetic retinopathy (21, 22), increased arterial stiffness (23, 24), or impaired renal function (25) along with aging and diabetes. Furthermore, receptor binding-induced activation of proinflammatory signaling pathways is associated with the development and progression of atherosclerosis (26) and nephropathy (25).AGEs have been localized in biological tissues by immunohistochemistry (27-29) and quantified with ELISA using monoclonal antibodies recognizing methylglyoxal-derived hydroimidazolone (30), imidazol...