Monday, January 13, 2014

Fibro theories--some more

I've been reading a book about Zombies . The end of chapter one tells about an experiment someone did on mice. When mice are lacking food, they go into a state of slowed-down animation (not fully suspended animation, but definitely a metabolically slower state) called torpor. Scientists discovered that the starving, torpor-induced mice were overloaded with 5' AMP (adenosine monophosphate). So, being scientists, they injected the 5' AMP into normal, healthy, food-secure mice and, lo and behold, the mice had an overreaction to the AMP and instantly dropped into a severe torpor.

So, reading about that and how AMP messes with thermoregulation, and I remembered reading about AMP before.

AMP is what happens when a molecule of ATP (adenosine triphosphate--the cell's energy molecule) uses up two of the phosphates in a sort of double-energy reaction. In normal cellular energy use and production, ATP and ADP cycle to each other, back and forth, rarely needing to use two phosphates and turn into AMP. When ATP does get turned into AMP instead of ADP, there is an enzyme called adenylate kinase that takes an ATP and an AMP and combines them to form two ADP molecules, which are then easily used to form two ATP molecules. There is not direct way to recycle AMP into ATP, though, and the body usually considers an excess of AMP a waste product.

Apparently it is well-documented scientifically that the energy production systems, on a cellular level, are broken in people with fibro. And they're broken in a way that leads to an excess of AMP (you see where I'm going, right?).

Current theory (of the vein that pushes the idea that ribose is good for fibro--like here http://corvalen.douglaslabs.com/D-Ribose%20Abstracts/Ribose%20in%20Fibromyalgia%200505%20Revised.pdf) says that the AMP is considered a waste product and broken down and thrown away by the cell, leaving the cell with no building blocks to make more ADP and therefore more ATP, and that is why people with fibro lack energy.

But I have a different idea, based on the mouse studies. I have no idea what the difference between AMP and 5'AMP is.  It's really hard to look up online (oddly--most everything else is easy to find online). As far as I can tell, they are the same.

So what if the excess AMP is not actually being broken down in people with fibro, but is instead inducing a state of torpor? Torpor includes a reluctance to move, a lower metabolism, and a lower body temperature, all of which are hallmarks of fibro. What if the enzymes that usually "babysit" the ATP cycle are broken, so they don't regulate the ratio of AMP:ATP like they're supposed to. That would mess up (if my research is right and I understood the chemistry right) all kinds of metabolic processes, including the insulin and lipid production/ break down processes (which are also known to be broken in people with fibro).

Because an excess of AMP in the muscles usually happens in time of stress or in times of heavy exercise, the body of someone with fibro would constantly be giving itself messages to rest and recover, and to stop muscle movement (like holding the arms out) way way way before it would be normal because the muscles would be getting the message that they were tired and hurting from too much exercise right off the bat. That would explain why Tim's muscles and mine feel the same when we hold our arms outstretched too long, but too long for him is several minutes, where too long for me is several seconds.

The ration of AMP:ATP also is related to what runners call the anaerobic threshold--the line where your body stops using energy effectively and your blood and muscles get bogged down with lactate, causing a lactate lethargy--that heavy feeling that you can't move your legs, and achy muscles. Science has apparently also proven that people with fibro reach the anaerobic threshold much faster than average healthy people do--like in response to regular life movement rather than exercise (which may be why so many of us have 2 "good hours" in the morning where we can get stuff done, and then we just feel like we don't want to move anymore...just like an athlete that hit that threshold).

Interestingly, the diabetes drug metformin can actually treat this AMP imbalance if it's caused by a breakdown of the enzyme 5' AMP-activated protein kinase (or AMPK), but there is some question if doing so can cause Alzheimers because having too much AMPK is connected with the development of Alzheimer's.  This might simply be a case of correlation and not causation. (People with Alzheimers have too much AMPK, but maybe that's because of the Alzheimer's and not the other way around).  I'm curious if anyone has tried to use metformin for Fibro?

There are other enzymes that could be the broken ones, of course, like adenylate kinase.

I am really curious if there is a messenger or regulatory enzyme that could be attached to many (most? all?) of the systems that are broken in fibro. Of if it could be something else? (For example, low ATP levels in cells make cell membranes unstable--could fibro patients be shedding cells at an abnormal rate? Fragile on a cellular level? Is the ATP issue causing the body to suck up phosphorus from the blood, which causes some of the symptoms of fibro and is scientifically correlated with chronic fatigue?).

Interestingly, the mouse study with AMP indicated that AMP is a key component of thermoregulation (namely, it can disable thermoregulation in mice). The link between thermoregulation breakdown and fibro is well established, but the cause has remained unclear (http://www.ncbi.nlm.nih.gov/pubmed/23887348 theorized it had to do with brown fat, for example, and a recent study found a connection between nerves, blood vessels, and thermoregulation in fibro http://www.examiner.com/article/new-study-indicates-a-cause-for-fibromyalgia-pain-to-be-found-the-skin).

So why does ribose help? Taking ribose increases the body's supply of adenosine, which allows it to make more ATP than it otherwise would. This increase in ATP once again balances the ratio of AMP:ATP. Apparently having this ratio right (not just having enough ATP) is the key to cells functioning properly and taking them out of the anaerobic threshold (allowing the body to process the lactic acid normally, removing the lactate lethargy) and also informing the cells that the muscles are no longer in a post-exercise recovery state all the time. It would also cancel the torpor and the metabolic issues associated with it, since they are regulated by an overabundance of AMP.   As one set of doctors suggested, it "reduces the metabolic strain" on the muscles.

Hmmm. All that from reading a book on Zombies.

I need to take some biochem classes so I can dig deeper.


1 comment:

Anda said...

Cool deductions, Mom. This is really interesting.