Pathogenic molecular handedness

[mark!]

Why is the enantiomer of a chiral molecule often considered to be a foreign, not-body-own pathogen?

Peptidoglycan, which makes up a great part of the bacterial cell wall, contains several of these molecules, such as D-alanin, whereas humans use the L-form, or other components like L-glutamic acid and D-glutamine, both of which only their mirror images are used by eukaryotes. N-Acetylglucosamine (GlcNAc) is also a component of peptidoglycan, and it is the monomeric unit of the polymer chitin, and chitin (which makes up the fungal cell wall) is a PAMP (pathogen associated molecular pattern). Semen contains L-fructose, which is also seen as not-body-own by the neutrophils of our innate immune system.

Is it usual that that mirror images are associated with bacterial/fungal/viral pathogens by our immune system? Are there more examples of this?

 

[BillTre]

Biochemistry is full of chiral molecules and their mirror image molecules.
This is one of the first things taught in biochem (or maybe organic chem, its been a long time since I have taken those courses).

Much of biochem/molecular biology functions occur through direct contact and binding between different molecules. It is difficult to think of functions in these fields that does not require specific meeting of different molecules.
The surface geometry of molecules, the distribution of different charges, areas of hydrophobicity and hydrophilicity (areas that either don't like to interact with water or that do like to), and probably other characteristics I am not remembering right now are all involved in determining what molecule will be able to successfully bind there.
The same principles are at work within molecules like proteins, keeping different parts together or apart, stabilizing their structure.
In addition, large molecules can vibrate and change shape to some extent, allowing both binding between a wide variety of structures, as well as the stabilization of particular shapes (conformational changes) when bound with particular other molecules.

A simple analogy would be your hands are chiral.
Gloves are also chiral (except really flexible plastic ones).
A nice fitting (non-flexible) glove will only fit nicely on to the hand of the proper chirality.
If you hand a nice fitting glove, but stiffened it into a particular shape (like a vulcan salute), then forced your hand into the glove would be forced into that shape also.

Not all chiral molecules will have mirror image molecules that are involved with pathogens or other weird things, but this is something that because it is distinct molecularly , can be used for almost any reason in biology, and biology (by its nature) will take advantage on anything it can.

 

[jim mcnamara]

There is Complement evasion - bacterial cell walls with L or R molecules to disrupt immune system response to their presence in a host.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2814840/

Edit: the 'complement thing' can be simplified as a lock and key operation, change the lock and the key no longer works.

Study looks at Staphylococcus aureus (the bacterium of MRSA fame that causes horrible and difficult to manage iatrogenic infections) - and its cell wall complements.
https://www.webmd.com/skin-problems-and-treatments/understanding-mrsa#1 Popular science version.

 

[mark!]

There is Complement evasion - bacterial cell walls with L or R molecules to disrupt immune system response to their presence in a host.

The complement system doesn't seem to have anything to do with molecular mirror images, or changing/flipping/inverting in any way. The article states that "a prominent example is the cell wall of Gram-positive bacteria, which prevents lysis" but I can't read anything about pathogenic mirror images. I'm interested in cases where only one enantiomer of a molecule, and not the other one, is pathogenic (or at least seen as 'not body own' by the immune system). I gave a few examples of this, but is this everything, or are there more examples?

Not all chiral molecules will have mirror image molecules that are involved with pathogens or other weird things, but this is something that because it is distinct molecularly , can be used for almost any reason in biology, and biology (by its nature) will take advantage on anything it can.

Of course, not all mirror image molecules are pathogens, but it's still interesting to me if it turns out that there are actually more cases of asymmetric pathogenic mirror image molecules like the ones I gave. If you know any, please share!

 

[jim mcnamara]

Enantiomers are not pathogenic in and of themselves. I guess you mean pathogens with enantiomers in the cell wall?

 

[zbikraw]

Your enantiomers inside larger molecules (especially biopolymeric ones) are mostly diastereomers, ie configuration reversal act on some from many "chirality centers" in a given molecule. Diastereomers have different physical and chemical properties, enatiomers differs only in relations with polarized light and other chiral molecules. In the living organizms we meet large excesses of one "proper" configuration over antipodal one, but frequently the "inproper" exist in a small amount. Most organizms contain enzymes acting specifically on "unnatural" compounds (isolated or being parts of larger molecules), so such ones must exist at least temporarily. Also popular are invertazes and racemazes which inverts configuration of specific "chiral centers" in biomolecules. Such situations are most frequently rationalized through evolutionary mechanizms. For example, proteinous cell walls are inherently unstable in the presence of proteolytic enzymes, typically present inside any living cell. Inversion of configuration of single chiral center of such biopolymer can make impossible good fit with active center of protease. In my opinion much better protection is provided by conformational change of biopolymer, frequent in a "stiff" state of a cell wall.

 

[BillTre]

I'm interested in cases where only one enantiomer of a molecule, and not the other one, is pathogenic (or at least seen as 'not body own' by the immune system).

Any protein toxin (pathogenic by my definition at least, there are many examples of protein or peptide toxins) that works by binding some receptor in an animal will probably work in only one of its enantiomeric forms. However, it is likely that being a protein, it will only (or predominately) be produced in one enantiomeric form. The alternative enantiomeric form(s) would like not bind the same receptor and therefore not have the same pharmacological effect.
It is, however, an example that, to me, seems trivial, since binding specificity is such that these forms will most likely be distinguished, as I tried to explain above.

I not clear on why you don't like @jim mcnamara's complement evasion example, since it would allow a pathogenic organism to better survive attack (and prolong its pathogenic lifestyle) by the immune system through the use of a different enantiomer.

 

[snorkack]

Basically, when reacting with a chiral substrate - which most biological substrates are - an enantiomer is simply a different compound.

 

[mark!]

Basically, when reacting with a chiral substrate - which most biological substrates are - an enantiomer is simply a different compound.

It's exactly because of this why I'm interested in more examples of molecules of which one of the two is considered not body-own.

Could anyone provide one more example of this?

 

[zbikraw]

It's exactly because of this why I'm interested in more examples of molecules of which one of the two is considered not body-own.

Could anyone provide one more example of this?

As I understand, you search for relatively simple molecular example. Outside of biomolecules with many "centers of asymmetry" there are many examples of the "kinetic resolution of racemate". When you react a "racemate" (1:1 mixture of anantiomers) witch chiral reagent given in less than stoichiometric amount, or reaction is stopped before quantitative consumption of the substrate, you may observe some optical activity in unreacted substrate. This is because of difference of velocities of reaction of enantiomers. The first monographic article about kinetic resolutions, by Henri B. Kagan, was published some 30 years ago in yearly "Topics in Stereochemistry".
When the chiral reagent is an enzyme, you can met complete enantiospecificity of reaction, one enantiomer of the racemic mixture react complety, and second don't react at all. Of course there are also examples of compete lack of enentiospecificity. "Enzymic resolutions" were discovered by Louis Pasteur, the first examples among other consist alcoholic fermentation of racemic sugars. Reactions of simpler molecules were discovered at the end of XIX century, among first examples was esterification of racemic mandelic acid by "natural" L-menthol. Remaining acid was about 1% "optically pure".
Kinetic resolutions are performed industrially for obtaining drugs, cosmetics, fragrances, etc.