L-form of amino acids

A possible explanation for the preference of living systems for the L (levorotatory) over the D (dextrorotatory) optical isomer may be associated with the stereoselective properties of layered minerals. To test this hypothesis, the rates of L- and D-histidine intercalation into HT layered compound was investigated using the pressure-jump relaxation technique (21). The rate constants and interlayer spacing based on this investigation are summarized in Table V. As shown the slightly enhanced rate for L-histidine suggests that relative chemical reactivity may be associated with natural selection of the L-form of amino acids in nature. 

On the other hand, free amino acid analysis represents a powerful tool to characterize different foods and beverages, monitor proteolysis, assess freshness, detect adulterations, and safeguard consumer health. The occurrence of some potentially toxic nonprotein amino acids (some of which are neuroexcitatory) in commercially available seedlings has been reported by different authors [197-199]. Due to the incapability of humans to utilize the o-isomers of amino acids (some of which are thought to be toxic), the enantiomeric separation of d- and L-form of amino acids is also an area of growing interest [196]. 

There are two major approaches to achieve enantiomeric separation of d- and L-amino acids. The first involves precolumn derivatization with a chiral reagent, followed by RP-HPLC [226], while the second involves direct separation of underivatized enantiomers on a chiral bonded phase [227], Weiss et al. [209] determined d- and L-form of amino acids by applying derivatization with OPA and chiral /V-isobutyryl-L-cysteine. 

It has already been mentioned that the origin of homochirality in nature can be viewed in terms of the controversy between determinism and contingency. Is the L form of amino acids determined by some physical law of nature or is it a matter of chance in chemical evolution ... 

A number of other racemases and epimerases may function by similar mechanisms. While some amino acid racemases depend upon pyridoxal phosphate (Chapter 14), several others function without this coenzyme. These include racemases for aspartate,113 glutamate,114-1153 proline, phenylalanine,116 and diamino-pimelate epimerase.117 Some spiders are able to interconvert d and l forms of amino acid residues in intact polypeptide chains.118119... 

The rotatory dispersion of amino acids in the visible range of the spectrum has been studied by several workers (Karrer and Kaase, 1919 Waser, 1923 Pertzoff, 1927). Recently, Patterson and Erode (1943) have published detailed results with thirteen a-amino acids. With most compounds studied, the dispersion is normal, i.e., the specific rotation [a] at a particular wave length can be expressed by a one-term Drude equation which has the form a = a/(X — Xo ), where a and Xo are constants. It is likely that, if measurements were extended to the far ultraviolet, amino acids, like many other optically active compounds, would exhibit anomalous dispersion, especially in those parts of the spectrum in which absorption of amino and carboxyl groups becomes significant. It appears, especially from the work of Patterson and Erode (1943) that the l forms of amino acids fall into three classes Group I consists of those amino acids which have a normal and positive dispersion for this class, to which most purely aliphatic amino acids belong, Xo has... 

Biological systems depend on specific detailed recognition of molecules that distinguish between chiral forms. The translation machinery for protein synthesis has evolved to utilize only one of the chiral forms of amino acids, the L-form. All amino acids that occur in proteins therefore have the L-form. There is, however, no obvious reason why the L-form was chosen during evolution and not the D-form... 

However, most natural peptides are composed of L-form a-amino acids and because of the ubiquitous prevalence of peptidases they have limited biostability, and consequently low bioavailability. Thus, a novel field of peptidomimetics has emerged in drug discovery, in attempts to design non-peptide compounds mimicking the pharmacophore and thus the activity of the original peptide. 

It is remarkable that virtually all amino acid residues in proteins are L stereoisomers. When chiral compounds are formed by ordinary chemical reactions, the result is a racemic mixture of d and l isomers, which are difficult for a chemist to distinguish and separate. But to a living system, D and L isomers are as different as the right hand and the left. The formation of stable, repeating substructures in proteins (Chapter 4) generally requires that their constituent amino acids be of one stereochemical series. Cells are able to specifically synthesize the l isomers of amino acids because the active sites of enzymes are asymmetric, causing the reactions they catalyze to be stereospecific. 

Figure 2.10. (Bottom) Difference between l and d amino acids. The two naturally occurring forms of amino acids differ in the position of the R group with respect to the backbone. An L-amino acid has the R group on the left if viewed along the chain from the free carbonyl end to the free amino end as shown. If the R group is on the right, it is defined as the d form. The predominant form found in proteins is the l form, although some amino acids in the d form are present in proteins.

Table 7-1 Difference in Taste Between the L-and D-Forms of Amino Acids...

A compound is chiral when it can occur in two forms that are mirror images of each other. The two forms (enantiomers) are very similar, hut not identical, for instance, like the right and the left hand of the same person. Classical synthesis produces both enantiomers in a 1 to 1 ratio. They cannot he separated hy normal physical means. Nature is, however, more selective. Here, only single enantiomers are formed. This can he used to separate D,L enantiomers of amino acids. The enzyme L-amylase produces selectively the L-amino acid from a mixture of the DL-acylamino acids. The D-acylamino acid remains unchanged and can he separated easily hy extraction or crystallization. 

C-terminal racemisation of a peptide and specific deuteration of the C-terminal residue can be achieved by cyclisation of the peptide to the peptide oxazolone and quenching in 2H20. This specific reactivity of the C-terminal amino-acid residue has formed the basis of a C-terminal analysis of peptides the C-terminal residue is the only one to be racemised in this way and the identity of the C-terminal residue is revealed by analytical methods for determining d l ratios of amino-acid mixtures (Section 4.18.2 Sih and Gu, 1995). 

Analysis of Amino Acids. Differentiation of the l- and D-forms of amino acids is essential because they differ in their biological and physiological properties. Although chromatographic columns that effect separations of chiral compounds could be used for analysis of solutions of these acids, a combination of a reactor containing a stereoselective immobilized enzyme and a chromatographic system provides the necessary selectivity for such analyses. 

Isomers that result from different arrangements of four different groups around the same carbon atom represent another class of stereoisomers called optical isomers. Optical isomers have the same physical and chemical properties, except in chemical reactions where chirality is important, such as enzyme-catalyzed reactions in biological systems. Human cells, for example, incorporate only L-amino acids into proteins. Only the L-form of ascorbic acid is active as vitamin C. The chirality of a drug molecule can also be important. For example, only one isomer of some drugs is effective and the other isomer can be harmful. 

There are several examples of d to l inversion of amino acids in the literature. D-Phenylalanine may have therapeutic properties in endogenous depression and is converted to L-phenylalanine in humans [145]. o-Leucine is inverted to the L-enantiomer in rats. When o-enantiomer is administered, about 30% of the enantiomer is converted to the L-enantiomer with a measurable inversion from l to o-enantiomer. As indicated in Fig. 13, D-leucine is inverted to the L-enantiomer by two steps. It is first oxidized to a-ketoisocarproate (KIC) by o-amino acid oxidase. This a-keto acid is then asymmetrically reaminated by transaminase to form L-leucine. In addition, KIC may be decarboxylated by branched-chain a-keto acid dehydrogenase, resulting in an irreversible loss of leucine (Fig. 13) [146]. D-Valine undergoes a similar two-step inversion process, and this can be antagonized by other amino acids such as o-leucine. The primary factor appears to be interference with the deamination process [147]. 

Andersson, L. Preparation of amino acid ester-selective cavities formed by non-covalent imprinting with a substrate in highly cross-linked polymers. React. Polym., Ion Exch., Sorbents 1988, 9, 29-41. 

Many of the biological and pharmaceutical compounds are chiral In nature. These compounds contain at least one asymmetric carbon atom or are molecularly as5mimetric. These have identical physical and chemical properties and differ only in their spatial configuration or in their optical properties. It is usual that Just one isomeric/enantiomeric form of these compounds is biologically active. For example, it is the L-isomers of amino acids which one finds in proteins and the D-isomer is biologically rejected. It is the D-glucose, not L-glucose that has been preferred by life. 

The conversion of L-amino acids in food proteins into D isomers generates nonutilizable forms of amino acids, creates peptide bonds resistant to proteolytic... 

For amino acids formed abiotically [15], the D/L ratio of amino acids converges to around 1. On the other hand, large enantiomeric excess of L-form... 

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