I took a very long break from the interwebs, to increase my productivity. It worked, a little too well - I started being accused of being a workaholic. So I'm dipping my toe back in
When I went back and used better search terms, I was able to find some research about ZAG and desquamation. Interestingly, a couple of papers referred to the ZAG protein as "lectin-like", suggesting it binds to amino sugar signaling molecules. But it also has
in vitro ribonuclease and protease activity. There's still no evidence that it directly degrades corneodesmosomes (that I could find), so its likely it plays some signaling role - like cathepsin D. In any case though, it's just one of many (and I mean
many) enzymes involved. That's why I don't get the singular focus on it from Cordain ::shrugs::.
MMPs (there are at least 28 that we know of) all have a lot in common. They are active in the extracellular matrix, which means they inhabit the entire body in a wide range of conditions. They are all secreted as prohormones with a cysteine switch, meaning they have to be "activated" in some way before they can function. They all have a Zinc ion in the active site, and are endopeptidases (meaning they cut proteins somewhere in the middle, rather than at the very end of the sequence). They have several conserved structural and sequence features that aren't really relevant for us. They are all proteases that degrade major structural proteins, like collagen, elastin, laminin, and proteoglycans.
But that's where the likenesses end... their functions are all over the place. An easy way to think of the ECM is as a manager and support staff. It micromanages the cells it contains, telling them how and when to develop, what to develop into, where to move, and how to alter what they're doing and producing based on whats going on in the environment. As such, the functions of metalloproteinases are nigh impossible to summarize. The reason they're important for cancer researchers is because they're involved in cell development and differentiation, which is the key process that goes awry in cancerous cells. For the same reason, they're important to growth and remodeling, as well as wound healing and immune response. They're not just workhorses though - it's likely their most important functions are as signaling molecules, causing the release of cytokines and acting on cell-surface receptors for other reasons.
For example, some MMPs are strongly associated with the inflammatory response. We often tend to focus on the middlemen of the process, inflammatory mediators such as interferons, chemokines, histamines, leukotrienes, etc - in a sense, MMPs are one step earlier in the process. This is the reason doxy and minocycline are the antibiotics of choice for acne - they have anti-inflammatory effects on top of their antibiotic effect. We know that the causes of acne vary in importance from person to person - in people whose acne is primarily caused by an over-active inflammatory response to fairly benign levels of bacteria, sebum, and desquamation, anti-inflammatories are particularly useful. Doxy/minocycline have few side effects, and thickened skin or psoriatic skin isn't among them. This suggests some kind of specificity in the inhibition. Its also proven useful in particular cases of both chronic and acute inflammation, with a focus on MMP-9 and MMP-2 (aortic aneurysms, multiple sclerosis, arthritis, atherosclerosis).
The cysteine switch is pretty simple - it's a part of the MMP proteins that literally folds over and puts a cysteine in contact with Zn ion in the active site of the enzyme. In at least some cases, the switch is part of the "propeptide" sequence, the part of the MMP that gets broken off to "activate" the enzyme. Cysteine has interesting functions in active sites because it includes an S-H. This group is called an especially reactive group called a thiol, and can do fun things like bind to metal ions, form disulfide bridges, and strongly interact with the substrate. Suffice to say, if the cysteine is in the right place, it can be crucial to a protein's function. In the case of the switch, the thiol forms a bond with the Zn ion, preventing it and the active site from taking part in any enzymatic reactions.
However, there is no real danger of a cysteine "deficiency" without a general protein deficiency, and putting topical sulfur on doesn't have any effect on the amino acid in general, or the MMP switch. It just.. doesn't work that way. Elemental sulfur is not the same thing as a thiol group on an amino acid. Cysteine isn't an essential amino acid. It's produced from methionine, a common essential amino acid that contains sulfur. Introducing any other sulfur compound will have no obvious influence on the production or use of cysteine, and certainly not on the cysteine switch.
Okay break time
PS: I wrote off Mercola as a scam artist a couple of years ago. I try really hard to give natural and alternative medicine proponents as much of the benefit of the doubt as I can, and of course there are those that are very honest, evidence based, and realistic. There are some that are honest, but clearly deluded and don't follow evidence-based practices. And then there are those like Mercola, who appear to purposely misguide people with scientific sounding mumbo jumbo that doesn't make any sense on the face of it to anyone with some scientific training. That blurb on sulfur is a perfect example.
Edited by greentiger87, 08 January 2012 - 12:51 PM.
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