And so we can look at the methionine residue as being able to react with the reactive oxygen species, and they set up a recycling program with one of the intermediates that Dr. Deeth is really focusing on recently, which is thioredoxin, and so it helps to recycle so that we can reuse our methionine. And so that if we look at a reactive oxygen species and we look at methionine and it becomes oxidized and then this thioredoxin can come back around with NADH and help us to be able to regenerate armothionine and deal with reactive oxygen species.
And I’m sorry he’s not here today because I think he’s one of the most brilliant researchers in autism. And he recently had said to me that _____(inaudible) [00:58:59.96], which we know is so central and what we all look at and was one of the first snips anyone look at years ago, and thioredoxin, their genes overlap in your DNA and share promoter. A promoter is what starts you off on the information to look at a piece of DNA. So it’s kind of like you…. the promoter allows you to open the door and read that piece of DNA. And what he relayed to me and what the research support says that COMT, which is so critical for our dopamine levels, and we look at so closely in terms of our support system in this methylation cycle, that it goes one direction and thioredoxin goes the other direction and they’re sharing a door that helps you to open to look at that DNA information. And so the fact that this thing turns around and helps you to recycle your methylene as part of this pathway to deal with oxidative stress is an unbelievable system of overlapping into relationship but it also gives us a sense why the body would collapse under the weight of this system breaking down.
And if anyone’s interested in the reference that’s why it’s here ,that if you look at right here let’s say being the door and you can either read this way for COMT or read this way for thioredoxin. They’re basically sharing a door for information, yet we’re using this so heavily COMT when look at the methylation cycle and this is so critical for keeping the oxidation and reduction status in the body in balance as well as recycling our methionine.
And so methionine is easily oxidized because it helps to basically soak up some of those reactive oxygen species. And in doing so it actually helps to protect certain tryptophan residues. And so we can look at tryptophan, if you recall is so central in serotonin, another one for our neuro transmitters. And they look particularly glutamine synthasse[01:00:15.15] (inaudible) where this is playing a role. So we’re looking at this relationship between methionine, the snips we look at, how tryptophan is tied in, where levels playable with OCD symptoms and serotonin, the effect of bacterial tryptophan and then the role metals play with respect to glutamate. And just to reiterate we’re talking here about the effect this can happen glutamate synthase and we’re looking at glutamate synthase to be able to move again from glutamate to a less toxic form.
And B-12 helps us to scavenge, especially hydroxy B12, some of the oxidized species. We also have a role here with glutamate synthase. And so when we have a lack of methionine we may have a problem here moving from glutamate to glutamine. When we had issues with Rubella we may be having a problem moving from glutamate to gavin we’ve talked about that before. When you have high levels of sulfites, with… which can happen if you have an SUO ex mutation, CBS up regulations or excess sulfites in the system that’s inhibiting at this point, and all of those serves to trap you with glutamate which can have excitotoxin activity and increased seizure activity in the body.
So let’s just take a second and like look at these interactions and why all of these pieces need to be addressed and why they come together. All right so if we look at the relationship between glutamate in this cycle. Glutamate decreases one of the enzymes that we’ll talk about in a minute that’s the backup route to dopamine. We know there is increased glutamate receptors in autism. Lack of methionine, some mutations in the pathway we look at impair one of the enzyme in this cycle. Sulfites due to additional mutations in the pathway, that may compromise our B12 or our ability to deal with sulfites affect other aspects of the neutrogenomics we look at in the pathway, and rubella can affect the third enzyme in the pathway. And so again looking at why we need to be conscious of the genetics, the supplements we need to bypass mutation in that pathway. What we take in the role of glutamate, getting those methionine levels where we need them, as well as paying attention to whether it’s bacterial or virus in the system. As well as the heavy metals that we were focusing on earlier. Another one of those light bulb moments. And I talked about this. These are very old slides from when I was first trying to explain what RNA. It’s from the RNA book as well as the RNA DVDs.
DNA is the information every cell in your body needs. It’s the information that tells you… your body how to make everything that it’s going make.
RNA is the part of the DNA that’s used, so it’s what makes my arm my arm; my leg my leg even though it’s the same DNA in every cell in the body.
Protein is what you actually see, and this we’ve talked about before. Okay. The light bulb moment. The way you start every protein that’s made in your body is with a methionine, okay. And the cycle we look at that generates methionine also generates all the building blocks for DNA and RNA. And so the interrelated pieces for what you need to survive come from the cycle were looking at. So that mutations or anything that’s impairing that pathway, feedback on this ability and so every single protein the information in the DNA, which is then translated to the RNA and what we use, everything starts with methionine. And we just finished saying that if you have mutations where you’re methionine levels are too low, that plays a role in terms of oxidative stress also, okay.
We can reverse… and these were some slides that we talked about last year at this conference. That it’s possible to have your body go backwards from SAMe and make methionine if it needs, but this is a very inefficient process and so what we want to be looking at is supporting the body properly so it doesn’t need to do this. Because if it needs to go backwards… burning cycle intermediates and generating high levels of Esta Denicio homocystine and adenosine which are non ideal for the system and of themselves create more damage to proteins if we need to go backwards. And so again it’s a futile cycle and we can go backwards to do this but we don’t want to do that, what we want to do is make sure that we are feeling the cycling properly, and also that were stabilizing our SAMe so that it’s not being damaged.
And one of the components that I have a lot of individuals taking is this sugar _____inaudible[01:06:00.10] and we have added that into the new hydroxyl B12 to help again to stabilize the system against this oxidative damage.
Also methionine is really critical when it comes to creatine and creatinine levels. And earlier in the doctor’s conference someone was bringing up chronically low creatinine levels and some in some of the kids. What I would suggest is go back, look at the methylation cycle, look at the mutation, see if we are for filling in properly. Do we even have enough methionine to be feeding into our creatinine levels?
And if we look at genetic mutations in creatine and creatine transporters and that part of the pathway, those are associated with language delays and development issues, okay. So mitochondria generate energy, but they also generate these reactive oxygen species that we need to deal with. Nickel can increase these as well as aluminum, and thalium can decrease our ATP for energy.
SAMe and methionine can help but also NADH and thioredoxin are involved, and we talked about that relationship that Dr. Deeth brought up, between thioredoxin and COMT. We can have a role of the trapping at glutamate if we have methionine damage and aluminum. The role of methionine in helping to protect some of other intermediates in the body and how critical methionine levels can be with respect to creatinine levels and perhaps language delays.
I’m going to shift a little now and look at the role of estrogen in helping to protect against mitochondrial damage and reactive oxygen species. And when the Times article came out this past week, their conclusion was that although this voltage gated calcium channel is seeing more frequently in males than females with autism and may play a role in the ratio of males to females in autism, that they didn’t know why it played a role. And for a while now a number of individuals have looked at the role of estrogen, but we can look at the role even more particularly because we’re going to see you in a few minutes that estrogen helps to control calcium in the body.
Okay so we already saw this slide. You have your energy cycle, we feed in…we feed into the mitochondrial membrane and we bounce electrons back and forth in the process we generate an energy gradient that drive our APT. Estrogen increases the efficiency of this, okay. So it’s helping the mitochondria to do a better job with energy generation. But it also helps to control calcium levels. And recall that too much calcium with glutamate that we just talked about can create excitotoxin damage in the body and damage to the nerves. So it’s critical to keep that calcium under control. Also in the absence of estrogen we don’t do as good a job of dealing with calcium regulation or reactive oxygen species, and so is the role of estrogen critical in helping to protect females to a certain except relative to males? So as a result I have added in a few more snips to the panel. The PEMT…aahm…snips because they are reactive to estrogen in the body, and we’ll look at that in a moment. So again we are looking at the role of estrogen in helping the body to hang on to and deal with calcium so we’re not ending up with calcium damage. And again we just talked about all that oxidative damage and estrogen’s playing a role there also. And well…well calcium may not be the main cause of some of the problems we see, it’s a critical part of the cascade that causes abnormalities.
This is just to illustrate how interrelated and connected calcium signaling is. Again to reiterate for you the roles that calcium can play and the voltage gated channel – this is what’s being talked about in the Times article – the voltage gated calcium channel. A genetic clue as to why autism affects more boys than girls and we’re looking at a voltage gated calcium channel. And again remember I just finished telling you that estrogen helps your body to control calcium, and that the way we open and close these voltage gated channels is by the energy we generate through that mitochondrial membrane which in the process of generating that energy, we create reactive oxygen species. And estrogen is one of the pieces that helps us to control those reactive oxygen species, which are then exacerbated by things like aluminum and nickel in the body.
Tying everything back together again, if we look at that specific voltage gated calcium channel, it is controlled by methylation. Ok so take a minute and think about this. If you have mutations in your methylation cycle and the cycle isn’t working properly, aside from what I just told you about the role it plays with respect to methionine, we also can’t control the voltage gated calcium channel properly, that we already know from the article that came out this past week, appears to play a role in terms of the problem of autism in males. And then layer in the affects of estrogen, aluminum reactive oxygen species as well as a needing to look at the role of the methylation cycle. And so that’s why we look at that pie chart, I am assuming you’re looking at the nutrition, that you’re looking at the methylation cycle, that you’re looking at where you have imbalances and supporting to bypass so that we at least don’t have to worry about the role of methylation but that’s under control because we know how to deal with that. And then we can systematically look at what bacteria we have, deal with the bacteria, get rid of the metals, clean up the swamp, see those excretion of metals that we’re seeing. And that’s how we’re seeing the improvements in the recovery. And so if we look at that voltage gated calcium channel that was just talked about this past week, look at the difference when it’s unmethylated and when it’s methylated okay.