| |
 |
| Author |
Message |
|
|
|
Sun Sep 20, 2015 3:25 pm  |
A rare genetic disease known as "Arterial Tortuosity Syndrome" (ATS) gets its name from the fact that these people have remarkably long, strangely curved and twisted major arteries. These malformations present a "tortuous" path for blood flow.
ATS patients also suffer from other symptoms, including laxity of the skin, and joint hypermobility and instability. ATS is described as a "connective tissue disorder" and, relatively recently, the cause of this disease has been identified as mutations in the gene that encodes GLUT10. GLUT10 is one of the family of GLUT transporters that transport sugars and the oxidized form of vitamin C (DHAA) through various cell membranes. This disease is being studied intensively by researchers around the world, not so much I suppose in search of a cure for this rare disease, but because it represents a rare human "gene knockout" model that enables researchers to examine the biochemical and physiological effects of a specific and known genetic flaw in human beings. Studies of disease have resulted in much of what is known about normal human physiology today.
For those familiar with vitamin C, and particularly with the cause and symptoms of scurvy, these studies are demonstrating some fascinating parallels. In fact, one paper published in 2010 specifically hypothesizes that the impairment of the ability to transport DHAA into certain cell compartments is the primary defect in ATS:
| Quote: |
| DHAA enters the endoplasmic reticulum (ER) using a hypothetical GLUT transporter. We hypothesize that GLUT10 is the uncharacterized transporter...In the ER, DHAA is reduced to AA by the protein disulphide isomerase, a subunit of prolyl hydroxylases. Prolyl- and lysyl-hydroxylases modify residues in collagens and elastin that stabilize the mature molecules. In ATS, loss of GLT10 would negatively affect the integrity of the deposit collagens and elastin...We believe that in the vessel wall defective elastin is the likely cause of tortuosity whereas outside of the cardiovascular system, like the joints and skin, the pathology probably reflects deposition of abnormal collagens. |
An interesting observation is that, if this hypothesis is correct, then it implies that it is the oxidized form of vitamin C (DHAA) that the cells must absorb for normal collagen and elastin formation. Of course, there are other studies and hypotheses, such as one published in 2012 that suggests mitochondrial dysfunction is involved in the pathogenesis of ATS. Nevertheless, impairment of DHAA transport remains the proposed causative factor in that study. Most recently, in a study published just this month (Sept 2015), researchers examined skin fibroblasts from ATS patients and found a wide array of not only biochemical changes, but dysregulation of gene expression. While arguing neither for nor against the concept that bad collagens and elastin is the primary defect, they propose that the lack of vitamin C transport could also result in abnormal expression of other genes that could also explain ATS pathogenesis. Once again, however, abnormal transport of DHAA is at the core of their hypotheses, and once again this study implies that normal transport of DHAA is necessary for normal, healthy skin and arteries.
None of this is inconsistent with the fact that human skin normally contains a very high ratio of DHAA to AA. It also supports the concept that DHAA is superior as a supplemental form of vitamin C for topical use, not only because DHAA is absorbed much better, but also because it appears to be the form that skin cells must absorb for proper collagen formation.
Links:
2010 Article
2012 Article
2015 Article |
|
|
|
|
|
|
|
|
Thu Jan 07, 2016 1:21 pm |
| Thank you for sharing this research. Fascinating! |
|
|
|
|
| Wed Apr 17, 2024 8:16 pm |
If this is your first visit to the EDS Forums please take the time to register. Registration is required for you to post on the forums. Registration will also give you the ability to track messages of interest, send private messages to other users, participate in Gift Certificates draws and enjoy automatic discounts for shopping at our online store. Registration is free and takes just a few seconds to complete.
Click Here to join our community.
If you are already a registered member on the forums, please login to gain full access to the site. |
|
 |
|
|
