I. ANALYTICAL METHODS 
IDENTIFICATION OF THE ELUSIVE AMINO ACID 
MILTON WINITZ 
Laboratory of Physiology, National Cancer Institute, National Institutes of Health, 
Public Health Service, U.S. Department of Health, Education and Welfare, Bethesda, Md. (U.S.A.) 
CRITERIA FOR ACCEPTANCE OF NATURAL OCCURRENCE OF AN @-AMINO ACID 
In 1931, in a brilliant review entitled The history of the discovery of the amino acids, 
VICKERY AND SCHMIDT! proposed certain criteria that should be met before any 
report of the existence of a new amino acid as a constituent of proteins be generally 
accepted as valid. These criteria are given in what follows: 
1. In order that an amino acid shall be accepted as a definite product of the hydro- 
lysis of proteins, it must also have been isolated by some worker other than its dis- 
coverer. 
2. Its constitution must have been established by synthesis and by demonstration 
of identity between the synthetic product and the natural racemized product, or by 
actual resolution of the synthetic product and preparation of the optically active 
natural isomer. 
3. The substance must be liberated by hydrolysis from a preparation of a protein 
of demonstrated purity and must be adequately characterized by analysis of salts 
and of typical derivatives. 
The protein-derived amino acids selected by VICKERY AND SCHMIDT, in 1931, which 
were acceptable according to these criteria, included all of those presently believed 
to occur in proteins with the exceptions of threonine, hydroxylysine, asparagine, 
glutamine and triiodothyronine, which had not yet been discovered, and included 
too p-hydroxyglutamic acid®; ?. Some 2 years later, ScHMipT? recommended that 
norleucine be added to the list of accepted amino acids because of its apparent con- 
formity with all of the required criteria. However, the seemingly irrefutable evidence 
upon which the acceptance of both f-hydroxyglutamic acid and norleucine rested 
was subsequently shown to be so tenuous that neither, at the present time, receives 
serious consideration as a constituent of proteins®. Such exceptions notwithstanding, 
the VICKERY-SCHMIDT criteria have served an invaluable role in that they prompted 
a generally more critical, as well as a more conservative attitude toward the accept. 
ance of anew amino acid. Thus, amino acids such as diaminoglutaric acid®: 7, hydroxy- 
aspartic acid®, 7, sarcosine’, a-aminoadipic acid®, norvaline!, ™ and a host of others 
have, at one time or another, been reported to occur in proteins, but such claims 
either have subsequently been proven questionable or have not yet received the ex- 
perimental support necessary for their general acceptance. 
In addition to the amino acids which are known constituents of proteins, a num- 
ber of amino acids have been found to occur in nature, either in the free state or in 
chemical combination in non-protein compounds of varying molecular size. Such 
amino acids have been detected in the biological fluids and tissues of various plants 
and animals, in the circulatory system, among the products of excretion, as inter- 
References p. 22/24 
