The Dark Side of DAmino Acids

Some D-amino acid enantiomers are associated with destructive and toxic effects for living organisms, in contrast to the above-presented "desired" deviant enantiomers. Consequently, biological organisms try to get rid of these enantiomers using various strategies. First of all, D-amino acids can be detected and eliminated by special proteins, called D-amino acid oxidases. Moreover, D-amino acids can be stored in deposits where they do not interfere with everyday metabolism (Rein 1992).

In some cases, the amount of D-amino acids constantly increases during ageing of the living organism. Eye-lenses serve as such an example where D-enantiomers of the amino acid D-aspartic acid were detected, which increase in concentration with age and denaturation induced by irradiation with P-particles. The mechanism of formation of D-aspartic acid probably involves stereoinversion of a specific aspartic acid residue (Asp-151) in the predominant lens protein called aA-crystallin. Additional post-translational modifications, including deaminations and oxidations were observed in crystalline lens protein samples of aged persons. The modifications

4 Similar developmental changes were reported for other organs such as testis, adrenal and pineal glands, mainly focussing on the d-amino acids d-aspartic acid and d-serine.

5 The authors proposed rather adventurously that the different behavior of the d- and l-serine enantiomers during hydrolysis might have caused the biomolecular asymmetry since the less decomposed l-serine might have had more opportunities to bind with peptide nucleic acid (PNA) than did d-serine (Nagata and Tagashira 1998).

appeared to be directly related to lens opacification, meaning that the eye-lens becomes less transparent (Momose et al. 1998; Fujii 2002). This by the way serves as a good example for Erwin Schrodinger's hypothesis that racemization is caused by an increasing incapability of the living organism to work against the force of increasing entropy. Here, the concept of "negentropy production" was considered as characteristic of the living matter.

These post-translational modifications were not observed in the lens protein samples of a young group. In these kinds of eye-medical studies, the eye-lens opacification was traced back to the amount of D-aspartic acid in the lens.

Moreover, other examples let us interpret the occurrence of D-amino acids in proteins as molecular markers for ageing (Fujii 2002): bones show relatively high concentrations of D-amino acids. In teeth, D-enantiomers of amino acids were identified as well. Profiles of D-aspartic acid in teeth revealed that aged living bodies deposit higher amounts of this deviant enantiomer, which was explained by an ongoing racemization of aspartyl residues in a protein over time (Fujii 2002). The older the organism, the higher is the concentration of D-amino acids to remove. There is thus speculation that molecules of deviating chirality may play a role in the processes of ageing itself (MacDermott and Tranter 1989).

Alzheimer's disease may also be linked to an increased amount of D-aspartic acid and D-serine enantiomers in the body. It is assumed that the deposition of the P-amyloid protein in the brain causes - or is involved in molecular processes in connection with - Alzheimer's disease. This protein is composed of 42 amino acid residues showing stereochemical inversion of the Asp-1, Asp-7, and Ser-26 amino acid residues in the case of Alzheimer's patients. It was thus suggested that the P-amyloid protein was aggregated by the racemization of these amino acid residues and accumulated in the brain (Fujii 2002 and references therein). Further studies confirmed that the racemization of an aspartic acid residue in the protein accelerated peptide aggregation and fibril formation observed for Alzheimer's patients.

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