Biochemical Homochirality

BIOGRAPHIC PHOTO 2.4. Emil Fischer. (Permission for use granted from the Edgar Fahs Smith Collection at the University of Pennsylvania Library.) 

D-(+)-Glyceraldehyde L-(-)-Glyceraldehyde FIGURE2.11. The molecular structures of the enantiomers of glyceraldehydes. 

Within months of the appearance of the article by the Dutch crystallographers Bijvoet, Peerdeman, and von Bommel on the absolute structure of (+ )-tartrate, Linus Pauling (Biographic Photo 2.5), Robert Corey, and Herman Branson published a milestone article on the helical structure of proteins [8]. Fischer had actually shown 50 years earlier that proteins were a linear chain of amino acids, but the overall three-dimensional structure of proteins was unknown. We introduced L-amino acids in Chapter 1 in our discussion of nomenclature, and we draw a 

Biographic photo 2.5. Linus Pauling. (Public-domain photograph from the National Institutes of Health.) 

In 1952, M. L. Huggins [10] calculated the interatomic distances for helical pol5 eptide chains and showed that one couldn t make a left-handed helix out of L-amino acids that fit the experimental X-ray diffraction data because a carbon from one turn came too close to an oxygen on the next turn. However, 

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Hazen RM, Filley TR, Goodfriend GA (2001) Selective adsorption of l- and D-amino acids on calcite Implications for biochemical homochirality. Proc Natl Acad Sci U S A 98 5487... 

The improved theoretical methods also invited to reinvestigate parity violating effects in biologically relevant systems [125,134,140,141,162,168, 169,178] and it could be demonstrated, that previous claims for a systematic stabilisation of amino acids in water, which based on lower level calculations, were not justified [140]. This finding gave again fresh impetus to the debate on possible relations between parity violating interaction and biochemical homochirality. 

This section on spectroscopically relevant molecules will be closed with camphor, for which early attempts to measure parity violating frequency shifts exist that provided an experimental upper bound of Aiz/i/ 10 [59]. As of yet, no calculations of the parity violating frequency shifts have been published, but Lazzeretti, Zanasi and Faglioni [136] computed the parity violating potential at the equilibrium structure of camphor within their one-component RPA method and predicted this potential to be of about —7 X 10 E h for the D-enantiomer, which would therefore be stabilised due to the parity violating interactions. This result has also been discussed in relation to the question of the origin of the biochemical homochirality, which will also be the main subject of the following section. 

As has been discussed in the introduction, the possibility of a relation between parity violating energy differences and the biochemical homochirality observed on earth has been noted by Yamagata [11] a decade after the discovery of parity violation in nuclear physics. Various different kinetic mechanisms have been proposed which could possibly amplify the tiny energy difference between enantiomeric structures to result in an almost exclusive chiral bias on a time scale relevant for the biochemical evolution. This aspect as well as other hypotheses regarding the origin of the biochemical homochirality have been discussed and reviewed multiple times (see for instance [33,37-39,190-193] and literature cited therein) so that we can concentrate here on the computational aspects of molecular parity violating effects in biochemical systems. 

By virtue of these results, it was repeatedly claimed that L-amino acids were systematically stabilised with respect to their D-counterparts due to parity violating weak interactions and this alleged stabilisation was frequently interpreted as evidence for a possible link between parity violating interactions and the observed biochemical homochirality in terrestrial organisms. 

J. Laerdahl, R. Wesendrup, P. Schwerdtfeger, Parity-violating interactions and biochemical homochirality, ChemPhysChem 1, 60-62. 

Although it may be tempting to extrapolate from the pyrimidine component of the aldehyde to argue about the origins of biochemical homochirality, the reaction itself consists of a water-sensitive alkylation that is far removed from what we think of as biology. Nevertheless, two striking features of this reaction are worthy of particular note ... 

One of the most important processes in the production of biochemicals is the 40,000 tons/yr lactic acid production involving the Lactobacillus oxidation of lactose. The MBR productivity increased eightfold compared to a conventional batch reactor with a 19-fold increased biomass concentration. Even a 30-fold increased production of ethanol was found upon coupling the Saccharomyces cerevisiae fermentation to a membrane separation. Other successful industrial applications involve the pathogen-free production of growth hormones, the synthesis of homochiral cyanohydrins, the production of 1-aspartic acid, phenyl-acetylcarbinol, vitamin B12, and the bio transformation of acrylonitrile to acrylamide. 

Whole-cell MBR have been utilized in a number of biochemical synthesis reactions. An example used industrially, is growth hormone biosynthesis by the bacteria E. coli (Le-goux et al [4.25]). Using the MBR allows the synthesis of this hormone free from pathogens, like those causing the Creutzfeld-Jacob disease, for example. Other industrial examples include the synthesis of homochiral cyanohydrins (Bauer et al. [4.26]), the production of L-aspartic acid [4.16, 4.27], and the biotransformation of acrylonitrile to acrylamide... 

For further aspects of such experiments, we refer to [5,15,16,22, 39,50]. When they work, they make possible, on the one hand, a measurement of Apv and with it a test of the various theories discussed above. These theories can then be used for the investigation of mechanisms of biochemical evolution of homochirality. On the other hand, the combination of exact measurements and calculations of Apv can also be used to obtain fundamental parameters of the standard model... 

This has important consequences for biochemical processes, for interactions of chiral compounds with organisms built from homochiral building blocks. The homochirality of receptors, enzymes and other key parts of an organism leads to a high degree of chiral discrimination, the ability to differentiate between enantiomers. Illustrative examples include smell and taste for example, the terpenoid carvone in its (-)-form smells of mint whereas its enantiomer, the (+)-form, smells of caraway (6). The two enantiomers of a pharmaceutically active compound can display different effects as well, while one shows the desired effect, the other might be inactive or display different, possibly harmful activity (7, 8). 

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