The presence of a glucose‐derived Maillard reaction product in the human lens

Nagaraj, Ramanakoppa H.; Sady, Candace

doi:10.1016/0014-5793(96)00142-1

Cited by 63 publications

(37 citation statements)

References 25 publications

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“…The stability of pyrraline toward alkaline hydrolysis was confirmed previously. 7,17) Very small amounts of the peptide-bound form of pyrraline were present in the urine, because alkaline hydrolysis did not affect the recovery of pyrraline, as shown in Figs. 2B and 2E.…”

Section: Fig 2 High Performance Liquid Chromatograms Of Pyrralinementioning

confidence: 93%

Determination of Urinary Pyrraline by Solid-Phase Extraction and High Performance Liquid Chromatography.

Kiyonami

Shimizu

Beppu

2001

Biological & Pharmaceutical Bulletin

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Long-lived proteins such as collagen, are partially or wholly modified in their molecular structure by glycation, resulting in accumulation of aminoketoses and formation of advanced Maillard reaction products, also known as advanced glycation end products (AGEs). Pyrraline, one of the major AGEs, is formed via a non-enzymatic reaction between reducing sugar and the epsilon-amino group of lysine residues of proteins, 1) and is thought to cause damage to tissues.2) AGE formation pathways are believed to consist of two types; one requires oxidative conditions (glycoxidation) and the other non-oxidative conditions. Pentosidine is a product of the former pathway [3][4][5][6] and pyrraline is a product of the latter pathway. 7)A previous study demonstrated by immunological methods that the pyrraline level is increased in diabetic sclerosed arterial and extracellular matrix, as well as in the sclerosed matrix of glomeruli.8) Another study also demonstrated by electrospray ionization (ESI) mass spectrometric detection an increase in pyrraline level of the plasma from uremic subjects.9) The level of plasma 3-deoxyglucosone, 10,11) an intermediate product in pyrraline and pentosidine formation, has been reported to increase in diabetic 12,13) and in uremic individuals. 14)Recently, chromatographic methods were applied in the measurement of the urinary level of pyrraline, and its increase in diabetic patients was demonstrated, 15,16) suggesting usefulness of the methods for evaluation of diabetic complications. However, there are few other reports describing chromatographic techniques for determination of pyrraline levels in biological fluids. In this paper, we describe development of a rapid and accurate method for the determination of urinary pyrraline using solid-phase extraction prior to separation and analysis by HPLC. Moreover, the proposed method was applied to analysis of urine samples obtained from healthy volunteers. MATERIALS AND METHODSChemicals L-Lysine, D-glucose, acetonitrile (HPLC grade) and trifluoroacetic acid (for amino acid sequencing analysis; TFA) were purchased from Wako Pure Chemical Ind., Ltd. (Tokyo, Japan) and used without further purification. The solid-phase extraction cartridge, Oasis TM HLB (3 ml, Waters Co., MA, U.S.A.), was used for pretreatment of urine samples. Other reagents obtained from commercial suppliers were of special reagent grade and/or analytical grade.Preparation of Pyrraline Standard Standard pyrraline was synthesized and purified, with some modifications, according to the method of Nakayama et al.1) L-Lysine (6.60 g) and D-glucose (8.10 g) were dissolved in 100 ml of 0.5 M sodium phosphate buffer (pH 8.5). The mixture was maintained at 80°C for 2 d, and then cooled. The cooled reactant was loaded onto a gel-filtration column (50ϫ1000 mm, Bio Gel P-2, 45-90 mm, Bio-Rad Labs., CA, U.S.A.) using 10% (w/v) acetic acid as the elution solvent at a flow rate of 36 ml/h. The absorbance at 298 nm of each fraction (16 ml/tube) was determined, and the fractions containing pyrraline wer...

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Section: Fig 2 High Performance Liquid Chromatograms Of Pyrralinementioning

confidence: 93%

Determination of Urinary Pyrraline by Solid-Phase Extraction and High Performance Liquid Chromatography.

Kiyonami

Shimizu

Beppu

2001

Biological & Pharmaceutical Bulletin

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“…Nagaraj and Monnier reported a structure named formyl threosyl pyrrole (14). Surprisingly, except for pyralline that originates from 3-deoxyglucosone (18), there is currently limited evidence for the existence of pyrrole adducts and crosslinks in the lens. Histidino-threosidine is first Maillard crosslink found so far according to our literature search, although a histidine adducts with 4-hydroxynonenal has been previously reported (19).…”

Section: Discussionmentioning

confidence: 99%

Isolation, purification and characterization of histidino-threosidine, a novel Maillard reaction protein crosslink from threose, lysine and histidine

Dai¹,

Nemet²,

Shen³

et al. 2007

Archives of Biochemistry and Biophysics

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We isolated a novel acid-labile yellow chromophore from the incubation of lysine, histidine and Dthreose and identified its chemical structure by one and two-dimensional 1 H and DEPT NMR spectroscopy combined with LC-tandem mass spectrometry. This new cross-link exhibits a UV absorbance maximum at 305 nm and a molecular mass of 451 Da. The proposed structure is 2-amino-5-(3-((4-(2-amino-2-carboxyethyl)-1H-imidazol-1-yl)methyl)-4-(1,2-dihydroxyethyl)-2-formyl-1H-pyrrol-1-yl)pentatonic acid, a cross-link between lysine and histidine with addition of two threose molecules. It was in part deduced and confirmed through synthesis of the analogous compound from n-butylamine, imidazole and D-threose. We assigned the compound the trivial name histidino-threosidine. Systemic incubation revealed that histidino-threosidine can be formed in low amounts from fructose, glyceraldehyde, methylglyoxal, glycolaldehyde, ascorbic acid, and dehydroascorbic acid, but at a much higher yield with degradation products of ascorbic acid, i.e. threose, erythrose, and erythrulose. Bovine lens protein incubated with 10 and 50 mM threose for two weeks yielded 560 and 2840 pmol/mg histidino-threosidine. Histidino-threosidine is to our knowledge the first Maillard reaction product known to involve histidine in a crosslink.

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“…Moreover, Verzijl et al recently used biochemical analysis to demonstrate that the advanced glycation end products (AGE) levels were linearly related to the degree of Asp racemization in both cartilage and skin collagen [17]. AGEs are formed by metal-catalyzed oxidation of glucose or Amadori products and are thought to be involved in aging or age-related disease such as diabetes [18], atherosclerosis [19], Alzheimer's disease [20] and cataract [21,22]. These findings are very similar the detection of D-β-Asp in age-related disease.…”

Section: A Discussion Of Factors That Favor Inversion and Isomerizatimentioning

confidence: 99%

Abnormal Protein Aggregation Due to the Presence of D-Aspartyl Residues in Cataractous Lenses

Fujii

Sugiyama

2012

Trans. Mat. Res. Soc. Japan

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A cataract is a clouding of the lens in the eye that affects vision. The one of the cause of the cataracts may be due to the abnormal aggregation of protein in lens. We found that two specific aspartyl (Asp) residues in αA-and αB-crystallins, respectively and one specific Asp in βB2-crystallin, from human eye lenses invert to the D-β-isomers to high degree during aging. The appearance of D-β-Asp isomers in proteins can cause major changes in the corresponding 3-D structure. Therefore, the presence of these isomers may be one of the triggers for abnormal aggregation, leading to cataracts. In fact, αA-crystallin containing large amounts of D-β-Asp obtained from cataractous patients of ~ 80 years of age has been shown to undergo increased aggregation to form massive and heterogeneous aggregates. Moreover, its chaperon activity, which prevents aggregation and insolubilization of other lenticular proteins, is reduced by 40%. Here we describe three important aspects of our research: (i) a method for detecting D-β-Asp at specific sites in particular proteins, (ii) a likely spontaneous mechanism by which Asp residues in proteins invert and isomerize to the D-β-form, (iii) a discussion of factors that favor such a reaction.

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The presence of a glucose‐derived Maillard reaction product in the human lens

Cited by 63 publications

References 25 publications

Determination of Urinary Pyrraline by Solid-Phase Extraction and High Performance Liquid Chromatography.

Determination of Urinary Pyrraline by Solid-Phase Extraction and High Performance Liquid Chromatography.

Isolation, purification and characterization of histidino-threosidine, a novel Maillard reaction protein crosslink from threose, lysine and histidine

Abnormal Protein Aggregation Due to the Presence of D-Aspartyl Residues in Cataractous Lenses

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