Methylation block question

[xrunner]

I understand more or less what happens when there's a methylation block (pls correct me if I'm wrong) where the key seems to be a block in the enzyme methionine synthase. Now that's where I start to get lost and would appreciate if somebody could help me out. I watched Rich's video a couple of times but I couldn't figure out the following:

I still don't understand how this can come about. I read from Rich posts that various stressors such as mercury, infections, stress etc. can trigger it but if methylation was working in the first place and enabled people to normally detoxify, it should have worked in every instance and so how come at some point it stops working?

Does the block directly affect other (secondary) enzymes, apart from methionine synthase?

How does the block actually work? Is it because a certain gene (which?) that makes this enzyme start malfunctioning or the enzyme is simply disrupted after it is made?

Do methylation reactions happen in all cells of the body or only in certain tissues or organs?

Thanks

 

[nanonug]

I understand more or less what happens when there's a methylation block (pls correct me if I'm wrong) where the key seems to be a block in the enzyme methionine synthase.

Yes, due to lack of co-substrate methylcobalamin.

I still don't understand how this can come about.

Glutathione is (eventually) created in the transsulfuration pathway, from homocysteine.

In cases of extended oxidative stress, intracellular glutathione gets progressively depleted. When glutathione gets depleted, intracellular cobalamin oxidizes, as glutathione protects cobalamin from oxidation by forming a glutathionylcobalamin complex. Because methionine synthase cannot work with oxidized cobalamin, the methylation cycle shows down, resulting in ever decreasing levels of homocysteine. And ever decreasing levels of homocysteine will result in ever decreasing levels of glutathione and the vicious circle is established.

Do methylation reactions happen in all cells of the body or only in certain tissues or organs?

To my knowledge, it happens absolutely everywhere.

 

[greenshots]

To put it simply, it works until it can't. ya know how you have something that's always in the fritz? Like a toaster or something. It partially works but as time goes on and you repeatedly use it, its going to break down. The genes/enzymes are either partially or fully defective and with constant use and exposure to known toxins that wipe them out (mercury) they eventually wear out too and don't do their jobs anymore.

But nothng works by itself so if the MTR enzyme goes out then you impact everything before and after it. Its sorta like an avalanche, like Rich said in the video lecture. As a child, you didn't have a ton of toxins coming in (unless you had the shots in the 1990's) so as time goes on, we accrue toxins, just like those little parasites on whales or ships. Only in our case, the toxins begin to overwhelm us with persistent exposures and eventually overwhelms that filter that isn't really working so well to begin with. The genes lead us to vulnerability and stack the deck against us or loads the gun but the epigenetic exposures, or environment, pulls the trigger.

Thats my take on it anyway.

Angela

 

[xrunner]

Thanks for your replies. Rich's post yesterday also answered some of the queries. Thanks.

 

[xks201]

Yes, due to lack of co-substrate methylcobalamin.



Glutathione is (eventually) created in the transsulfuration pathway, from homocysteine.

In cases of extended oxidative stress, intracellular glutathione gets progressively depleted. When glutathione gets depleted, intracellular cobalamin oxidizes, as glutathione protects cobalamin from oxidation by forming a glutathionylcobalamin complex. Because methionine synthase cannot work with oxidized cobalamin, the methylation cycle shows down, resulting in ever decreasing levels of homocysteine. And ever decreasing levels of homocysteine will result in ever decreasing levels of glutathione and the vicious circle is established.



To my knowledge, it happens absolutely everywhere.

I thought the problem in under methylation was high homocysteine not low?

 

[hixxy]

Please ignore what you have learnt from Pfeiffer! It just confuses things -- a lot! Methylation is far more complicated then simply over and under methylation. Likewise the markers that Pfeiffer doctors use for determining uder and over metylation are unreliable at best.