Biochemistry of Amino Acids - A. Majster 1961

Natural Amino Acids
Natural D-Amino Acids

"...If the mysterious influence that determines the specific Asymmetry of natural products were to reverse its direction or sign, the constituent elements of living things would be converted into their mirror image, and we might perhaps be confronted with a new world. Who can foresee what the Organization of living beings would be like if glucose were to change from dextrorotatory to levorotatory, and Blood albumin from levorotatory to dextrorotatory?

We are faced with riddles whose solution will require no small effort in the future and which even now prompt scientists to profound reflection." Pasteur (1860).

At present, there is no conclusive Evidence for the presence of D-Amino Acids in PLANT AND ANIMAL Proteins. Because amino acids may undergo some racemization during the acid Hydrolysis of Proteins, it is difficult to rule out the presence of small amounts of D-amino acids in proteins. Not long ago, Kögl and Erxleben [350] reported the presence of certain D-amino acids (especially D-glutamic acid) in tumor proteins. Kögl and his coworkers suggested that THE ORIGIN OF tumors itself is somehow related to the presence of D-amino acids. The data of Kögl and his associates sparked a vast number of experimental studies and became the subject of extensive Structure/133.html">Discussion. Most researchers, when attempting to reproduce Kögl's data, were unable to confirm his results. Miller [351] recently published a review devoted to a detailed discussion of this question. Although most researchers do not share Kögl's viewpoint, the presence of small amounts of D-glutamic acid in proteins cannot be completely excluded. Kögl [352] has published further data consistent with his initial observations, and recently other researchers have also reported the presence of D-amino acids in animal Tissues [353, 354]. The question remains unresolved to this day; presumably, more advanced Methods of hydrolysis and isolation must be applied.

Class="center">Table 4 Natural D-Amino Acids

Although the presence of D-amino acids in proteins has not been proven, their occurrence in the free state and as peptides in the Cells of various microorganisms is beyond doubt. As can be seen from the data presented in Table 4, the expression "natural configuration" has lost its meaning.

Many Antibiotics, including polymyxins, tyrocidine, and gramicidin, contain D-amino acid residues. Penicillin contains D-penicillamine (β,β′-dimethyl-D-Cysteine) (p. 76). D-Aspartic acid and D-phenylalanine are found in hydrolyzates of Bacillus brevis and apparently exist in a bound form within the cells of this microbe [359]. D-Alanine is a component of the cells of Lactobacillus arabinosus and certain other microorganisms that utilize this amino acid for growth [355]. D-Aspartic acid is also required for the growth of some lactic acid bacteria and is present in hydrolyzates of these microorganisms [360].

D-Glutamic acid is found in hydrolyzates of L. arabinosus [364] and in the polypeptide that forms part of the cell capsule of B. anthracis and related organisms (p. 72). D-Proline was isolated from acid hydrolyzates of ergot Alkaloids as early as 1935 [379]; this observation has been reproduced by other researchers [380]. However, there is now evidence indicating that in the ergot alkaloids themselves, prior to hydrolysis, proline has the L-configuration [381]. allo-D-Isoleucine, found in actinomycin hydrolyzates [382, 383], probably also arises during hydrolysis As a result of the epimerization of L-isoleucine, which is a component of this peptide [384].

The distribution of D-amino acids still appears somewhat restricted. However, it must be taken into account that research on this subject began relatively recently and is receiving a great deal of attention; this gives reason to anticipate the future discovery of new D-isomers in natural products. It is rather difficult to judge The Role of D-amino acids in biological objects; their presence in nature provides at least a teleological basis for the existence of D-Amino Acid Oxidase (p. 184). Other enzyme systems that carry out the METABOLISM of D-isomers also exist. Obviously, D-Amino acids can be formed through the action of Bacterial Amino Acid racemases (p. 240). D-Amino acid residues incorporated into certain antibiotics confer enhanced stability on their molecules, making them less susceptible to the action of peptidases. In this regard, It is interesting to note that the glutamic acid entering into the composition of B. subtilis cellular proteins has the L-configuration, whereas the glutamic acid isolated from cell capsules is the D-isomer. The assumption that the biological activity of certain antibiotics is due to the presence of D-amino acid residues in their molecules is devoid of factual basis.

In some species of lactic acid bacteria, the content of D-alanine ranges from 1 to 2% of the dry weight of the cells; about 40% of this D-alanine can be extracted from the cells with hot trichloroacetic acid, while the remainder apparently exists in a bound form within The Cell wall fraction [385]. D-Glutamic acid is also contained in the cell wall of lactic acid bacteria; a body of evidence indicates that D-amino acids in the Introduction/37.html">Bacterial cell wall are bound to aminosugars¹ [368].

To determine the optical configuration of amino acids, a micromethod is used based on the employment of D- and L-amino acid oxidases (p. 183) combined with paper Chromatography. When hydrolyzates of casein, ultrafiltrates of normal human plasma, urine, and CEREBROSPINAL FLUID are treated with L-Amino Acid Oxidase preparations, the disappearance of amino acids susceptible to the action of this enzyme is observed. This does not occur when the same Materials are treated with D-amino acid oxidase. Hence, it follows that the major part, if not all, of the amino acids present in these objects has the L-configuration [577]. The presence of D-alanine in the blood of the insect Oncopeltus fasciatus was established using this same method [578].

In addition to the D-isomers listed in Table 4, there are Naturally Occurring Amino Acids with multiple asymmetric carbon atoms in which at least one optical center has the D-configuration. Such amino acids include L-Threonine, meso-diaminopimelic acid, allo-hydroxy-L-proline, and "methyllanthionine".

¹ In recent years, A number of authors (Park, Strominger, et al.) have established that nucleotide derivatives of mucopeptides containing D-amino acids participate as precursors in The formation of high-polymer mucopeptides of the bacterial cell wall, such as, for example, uridyldiphospho-N-acetylgalactosaminyl-O-lactyl-L-ala-D-glu-L-lys-D-ala-D-alanine (in Staphylococcus aureus) or an analogous compound containing a meso-diaminopimelic acid residue instead of a Lysine residue (in E. coli) (see p. 96, as well as J. L. Strominger, S. S. Scott and R. H. Threnn, Feder. Proceed. 18, 334 (1959)). The accumulation of such products in bacterial cells is observed in the presence of penicillin, Tetracyclines, and Other Antibiotics that inhibit The Biosynthesis of the bacterial cell wall substance. — Ed. note