d-Amino Acid Formation Induced by a Chiral Field within a Human Lens Protein during Aging

Fujii, Nobutaka; Harada, Kaoru; Momose, Yuko; Ishii, Noriyuki; Akaboshi, Mitsuhiko

doi:10.1006/bbrc.1999.1279

Cited by 67 publications

(64 citation statements)

References 19 publications

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“…Proteins of the lens have long half-lives; therefore, various posttranslational modifications, such as the formation of disulfide bridges, 18 deamidation of asparaginyl and glutaminyl residues, 18,19 racemization of aspartyl residues, 1,3 and advanced glycation, have been reported. 20 These modifications may cause the formation of high molecularweight protein aggregates that can lead to the formation of cataracts.…”

Section: Discussionmentioning

confidence: 99%

“…This hypothesis is supported by the fact that the irradiation of ultraviolet rays is an accelerator of racemization and the risk factor of drusen formation. [1][2][3]8 To reveal the role of the Damino acids in the development of age-related macular degeneration, further studies, including mass spectrometry of drusen and in vivo and in vitro, are needed regarding the biological effect of D-amino acids in relation to angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…For this reason, D-Asp acid in living organisms is considered a useful marker of the aging process. 1,4,5,8,9,12 We previously reported the presence of D-isomers at Asp-58 and Asp-151 in ␣-A-crystallin 13 and at Asp-36 and Asp-62 in ␣-B-crystallin 14 from aged human lenses. The D-Asp formation was accompanied by isomerization from the natural ␣-Asp to the abnormal ␤-Asp through a succinimide.…”

mentioning

confidence: 99%

“…The D-Asp formation was accompanied by isomerization from the natural ␣-Asp to the abnormal ␤-Asp through a succinimide. 1 This leads to the formation of four isomers, namely, the normal L-␣-Asp plus the biologically rare L-␤-Asp, D-␣-Asp, and D-␤-Asp in proteins. Among the uncommon isomers, D-␤-Asp is the major isomer found in elderly tissues.…”

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confidence: 99%

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Localization of D-β-Aspartic Acid–Containing Proteins in Human Eyes

Kaji

Oshika

Takazawa

et al. 2007

Invest. Ophthalmol. Vis. Sci.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Localization of D-β-Aspartic Acid–Containing Proteins in Human Eyes

Kaji

Oshika

Takazawa

et al. 2007

Invest. Ophthalmol. Vis. Sci.

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“…In addition, the D/L Asp ratio was higher in the water insoluble proteins (Masters et al 1978), which was interpreted as evidence for a loss of the native protein conformation. Subsequently Fujii's group (Fujii et al 1999a) identified selected sites on proteins, such as alpha crystallin, as being particularly prone to racemisation.…”

Section: Introductionmentioning

confidence: 99%

Racemisation and human cataract. d-Ser, d-Asp/Asn and d-Thr are higher in the lifelong proteins of cataract lenses than in age-matched normal lenses

Hooi

Truscott

2010

AGE

105

122

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Astract Several amino acids were found to undergo progressive age-dependent racemisation in the lifelong proteins of normal human lenses. The two most highly racemised were Ser and Asx. By age 70, 4.5% of all Ser residues had been racemised, along with >9% of Asx residues. Such a high level of inversion, equivalent to between 2 and 3 D -amino acids per polypeptide chain, is likely to induce significant denaturation of the crystallins in aged lenses. Thr, Glx and Phe underwent age-dependent racemisation to a smaller degree. In model experiments, D -amino acid content could be increased simply by exposing intact lenses to elevated temperature. In cataract lenses, the extent of racemisation of Ser, Asx and Thr residues was significantly greater than for agematched normal lenses. This was true, even for cataract lenses removed from patients at the earliest ages where age-related cataract is observed clinically. Racemisation of amino acids in crystallins may arise due to prolonged exposure of these proteins to ocular temperatures and increased levels of racemisation may play a significant role in the opacification of human lenses.

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Amino acid sequence and D/L‐configuration determination methods for D‐amino acid‐containing peptides in living organisms

Iida

Santa

Toriba

et al. 2001

Biomedical Chromatography

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D-amino acid-containing peptides with biological activities have been isolated from invertebrates and amphibians, and partial racemization of amino acid residues in mammalian peptides associated with aging and diseases have been discussed. Here, we review the amino acid configuration determination methods in these peptides and recent progress of simultaneous determination method for sequence and configuration of amino acid residues. The applicability of C-terminus sequence analysis and mass spectrometry to configuration determination of amino acids is also discussed.

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d-Amino Acid Formation Induced by a Chiral Field within a Human Lens Protein during Aging

Cited by 67 publications

References 19 publications

Localization of D-β-Aspartic Acid–Containing Proteins in Human Eyes

Localization of D-β-Aspartic Acid–Containing Proteins in Human Eyes

Racemisation and human cataract. d-Ser, d-Asp/Asn and d-Thr are higher in the lifelong proteins of cataract lenses than in age-matched normal lenses

Amino acid sequence and D/L‐configuration determination methods for D‐amino acid‐containing peptides in living organisms

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