Amino Acids of Uncertain Biological Significance

CERTAIN AMINO ACIDS OF UNCERTAIN BIOLOGICAL SIGNIFICANCE 

There is very little exact information about the catabolic pathways of the three amino acids, a-aminobutyric acid, norvahne, and norleucine. They have been termed unnatural amino acids because they have not been found to occur in proteins. However, from the general knowledge of the metabolic reactions of the amino acids and of the deaminated carbon residues, their metabolic fates can be predicted with a high degree of probability. Tt has been established that the animal organism can tolerate 

Small amounts of this amino acid are found to be widely distributed in the nonprotein extracts of tissues by paper chromatography. Dent has reported its appearance in the urine of a patient with hepatic disease following the administration of large amounts of methionine. Lien and Greenberg have shown that is formed from threonine in the animal body. 

Norvaline is strongly ketogenic. The L-form is attacked by L-amino acid oxidase and the D-form by D-amino acid oxidase. Its susceptibility to transamination has not been reported. Its ready oxidation to CO2 in the intact animal has been observed by Hassan and Greenberg. More of this amino acid is excreted unchanged in the urine than is leucine. Evidence for the formation of a 2-carbon unit was also obtained in this work. This leads to the scheme for the catabolism of norvaline shown in Fig. 8. 

Norleucine also is readily oxidized to CO2 in the intact animal. A few per cent is excreted unchanged in the urine. The L-amino acid is transaminated by heart muscle. The D-form is strongly attacked by D-amino acid oxidase. A plausible scheme for its catabolism is given in Fig. 9. 

Certain Amino Acids of Uncertain Biological Significance 

The three amino adds, a-aminobutyric add, norvaline, and norleucine, have been termed unnatural because they have not been foimd to occur in proteins. However, a-aminobutyric acid and norleucine have been foimd to occur in natural materials. The advent of column and paper chromatography led to the discovery that small amounts of a-aminobutyric add are widely distributed in the nonprotein extracts of animal tissues and that it is excreted in the urine. Precursors of this amino add in the animal organism are threonine (68) and methionine (ISB, ISS). 

Norleucine is a component of the antibiotic DON (6-diazo-5-oxo-L-norleucine). It acts as a glutamine antimetabolite and represses the growth of certain experimental tumors (see 135b). 

It has been established that the animal organism can tolerate and metabolize these amino acids (136, 137) as well as most of the D-amino acids (138). 

The metabolic fate of these three amino acids has been studied mainly in the laboratory of the author. 

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VI. CERTAIN AMINO ACIDS OF UNCERTAIN BIOLOGICAL SIGNIFICANCE... 

VI. Certain Amino Acids of Uncertain Biological Significance... 

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