Submitted to: Book Chapter
Publication Type: Book / Chapter
Publication Acceptance Date: September 8, 2010
Publication Date: January 1, 2012
Citation: Friedman, M., Levin, C.E. 2012. Nutritional value of D-amino acids, D-peptides, and amino acid derivatives in mice. Polleioni & Servi, S., editors. Unnatural Amino Acids Methods and Protocols. New York Dordrecht Heidelberg London. Humana Press. Vol. 794, p. 337-356. Interpretive Summary: As part of an effort to develop a better understanding of the nutritional value and safety of novel amino acid derivatives (D-amino acids, cross-linked amino acids, oxidized amino acid, Maillard browning products) formed during food processing, we previously published a series of papers in the Journal of Nutrition and in Nutrition Reports International on a method to determine the nutritional value and potential toxicity of unnatural amino acids in mice. The bioassay uses an all-amino acid diet in which an essential amino acid is replaced by the unnatural amino acid. Mice provide a good in vivo model to study the nutritional utilization and biological effects of unnatural amino acids. A major advantage of mouse bioassays is that they require about one-fifth of the test substance needed for rats and can be completed in 14 days. The method can be used to determine the nutritional value and safety of hundreds of unnatural amino acids present in processed foods and synthesized by plants, bacteria, and animals. This paper was prepared in response to an invitation from Loredano Pollegioni and Stefano Servi, Editors of the widely circulated series of volumes entitled Methods in Molecular Biology, to contribute an experimental protocol to a forthcoming volume in this series entitled Unnatural Amino Acids. The research protocols are all peer-reviewed. The updated description of the bioassay will facilitate its use by the scientific community.
Technical Abstract: This paper describes a method for determining the nutritional value of D-amino acids, D-peptides, and amino acid derivatives using a growth assay in mice fed a synthetic all-amino acid diet. A large number of experiments were carried out in which a molar equivalent of the test compound replaced a nutritionally essential amino acid such as lysine (Lys), methionine (Met), phenylalanine (Phe), and tryptophan (Trp) as well as the semi-essential amino acids cysteine (Cys) and tyrosine (Tyr). The results show wide-ranging variations in the biological utilization of test substances derived from Cys, histidine (His), isoleucine (Ile), Lys, Met, Trp, Tyr, and valine (Val). The method is generally applicable to the determination of the biological utilization and safety of any amino acid derivative as a potential nutritional source of the corresponding L-amino acid. Because the organism is forced to use the D-amino acid or amino acid derivative as the sole source of the essential or semi-essential amino acid being replaced, and because a free amino acid diet allows better control of composition, the use of all-amino-acid may be preferable to protein-based diets.