Appearance of D-amino acids during aging: D-amino acids in tumor proteins

In 1939 Kögl and Erxleben [1-4] reported that tumor proteins contain appreciable amounts of D-amino acids, specifically glutamic acid, valine, leucine and lysine, implying that both the initiation and autonomous character of tumors depends on the formation and maintenance of these D-amino acids in the cell proteins. This postulate remained highly controversial for over 10 years, during which time several papers both supporting and refuting this hypothesis were published. The dispute existed almost entirely between Kögl, a vigorous and able protagonist at the University of Utrecht, Netherlands, and an impressive array of equally vigorous and able dissenters in the United Kingdom and Germany. An excellent review of both sides of this controversy was written by Miller in 1950 [5]. After many years and much effort the controversy then seemed to be put to rest. However, more than 40 years later the development of much more refined analytical techniques for the resolution and detection of amino acid enantiomers provided more definitive evidence that D-amino acids are not common to all tumor tissues and probably are not integral to the cancer process. This is not surprising when one considers that a tumor consists of fast-growing cells. Thus, there would not be sufficient time for any L-amino acid to racemize to the D isomer. Some D-amino acids may originate in foods consumed, but it is uncertain whether enzyme systems are able to incorporate D-amino acids into tumor proteins during growth. Nevertheless, if significant levels of D-amino acids were to be found in tumor proteins, the implications could be far-reaching. Confirmation of the presence of D-amino acids at any concentration in tumors would provide new insights into the mechanism for autogenesis and maintenance of tumors.