Good Molecules from Cataclysms — Molecular Recycling

 

 

 

 

 

 

 

 

 

 

Image:  Human GAPDH Molecule 1U8F, from rcsb.org

 

Many of the structural and enzymatic components of the epidermis are destroyed during the final cataclysmic stages of epidermal differentiation. Keratins and filaggrins form amino acids and contribute to the water-retaining ability of the epidermis and its” natural moisturizing functions”. Many of the synthetic enzymes of the epidermis are also metabolized. After proteolysis, at least one synthetic molecule forms a 30-amino acid peptide that has both immune-modulating and antifungal properties (Wagener et al, 2012 — JID.2012.254). Many decades ago antibiotics were found in the environment or in soil samples. Now there is a new paradigm looking for “natural” anti-microbial molecules made by the body.

GAPDH (glyceraldehyde-3-phosphate dehydrogenase) is important for glycolysis, transcription and apoptosis. There is a 30-amino acid fragment from its N-terminal that is internalized by Candida albicans, leading to fungal cell death. What great recycling!  After GAPDH has fulfilled its synthetic role, at least one portion of the molecule can protect the epidermis by exterminating at least one yeast species — an organism that is a nuisance for some individuals and a serious pathogen for others.  A great example of both the wisdom and the economy of the body.  If a molecule gets beat up and can’t fulfill its original function, buff it up (in this case: cut off a segment) and apply it to another function. Wagener et al report interesting details on the discovery and the action of the 30-amino peptide from GAPDH. More importantly, this model expands our thinking on how to look for epidermal molecules that may have more than one physiological function.

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