Methionine cycle

[Hope78]

Hi!
I spent the weekend trying to make sense of my lab testings concerning particulary the methylation cycles.

I guess I found out sth. Hard to explain in English but I do my very best.

As I am very low in methionine I stumbled about something called the methionine cycle. It's entirely new stuff for me. There seem to be some typical "error sources" in converting homocysteine to methionine, like defiencies in active Folate, B12 and B6. B6 is especially important concerning the transsulfuration pathway (and producing glutathione needed for detox).

So I looked at my lab tests: the substances I am defient in, the normal ones and the elevated ones.

I am low in methionine. But why? Often the cause is a (functional) deficiency in B6, B12 and folate. But if that was the cause, doesn't homocysteine has to be elevated? Or methylmalonat? It's normal in my case.

I also noticed I have very, very elevated levels of glutathione (overall glutathione elevated, also reduced one, oxidiced one normal). Ok, but why do I have normal to elevated levels of glutathione why all the other substances which require methionine or its active form s-adenosylmethionine are defient (like taurine, l-caritine, Q19, melatonine, epinephrine and others).

IF there was a b6 deficiency I should not have enough cysteine or glutathione.
IF I was defient in B12 there should be elevated methylmalonat.
IF I was absolutely defient in methionine and B6, I sould also be defient in glutathione and cysteine.

So my guess is: My body is actually able to degrade homocysteine to methionine. BUT: all the methionine is easily "branched off" for glutathione production (my body seems to prioritize detoxing), leaving not enough over for the other methionine-dependent processes like methylation by SAMe.

That would also describe my muscle weakness/pain, as I am very defient in Q10 and L-carnitine (both being dependend on methyl groups from SAMe). Also the degradation from norepinephrine to epinephrine needs a methyl group what explains why I am high in dopamine & norepinephrine (comt polymorphism!) and very, very low in epinephrine.

But one question still remains: why does my body use up this much gluthathione?
I have very high citrulline, indicating nitrostaive stress. I have also leaky gut. And I don't know about heavy metals and other toxins in my body.

But to me it seems as there is a great need for detoxification and therefore methylation via SAMe is slowed down. Maybe it's only one peace of the whole picture.

But where to start with?
- supplementing the "raw material", methionine?
- supplementing SAMe (could be critical as I have the slow comt and am very sensitive to dopamine, norepinephrine)
- supplementing glutathione (but does this make sense as my glutatione does not seem to be depleted?)
- supplementing B-vitamins to make methionine out of homocysteine faster (or more oft it?)

- and, probably most improtant: finding out why I have to detox so much (but how??)

Ok, I hope it became a bit clear what I wanted to explain. Not easy for me in a foreign language

 

[PeterPositive]

What are you levels of methionine and homocysteine?
As regards diet... what is your daily intake of protein, rouglhy? And from what source?
Do you have any digestive issues? IBS, IBD... ?

cheers

 

[Hope78]

Hi PeterPositive,
ok, let's see....

methionine: 21 nmol/ml ref.range 25-49

homocystein: 7,4 nmol/ml normal: <= 9

glutathione total (GSH + 2GSSG): 133 nmol/l ref range 783-134
glutathione reduced (GSH): 1583 nmol/l ref range 39-1146
glutathione oxidized ((GSSG): 25 nmol/l ref range <72
glutatione total/reduced ratio: 1,0 ref range > 0,8

In the morning I am eating a plant based protein meal. Once or twice a week I eat meat (mostly chicken, only organic). Small amounts of milk and cheese. Beside that lots of vegetables, fruits, whole grain products.

No IBS, but leaky gut, histamin intolerance, candida

 

[PeterPositive]

It seems possible that diet may not deliver enough methionine, especially since you have few servings of animal proteins each week.

Also your low value of methionine doesn't strike me as a major issue, it's just a bit low and I don't think it should cause any alarm. Probably a bit more animal proteins or specific veggies high in that amino acid could help fix the problem. (e.g. spinach, broccoli, sweet potatoes...)

By the way in this paper:
http://www.sciencedirect.com/science/article/pii/0009898178904321
they mention a serum range for methionine between 20 and 60 nmol ... so by those standards you're fine


cheers

 

[Hope78]

Also your low value of methionine doesn't strike me as a major issue, it's just a bit low and I don't think it should cause any alarm

That's right, could be much lower.
But why is it then that I am also low in substances depending on methionine/SAMe except glutathione?

Recently a test came back, suggesting lowered methylation activity and recommending to take methionine (was an estrogen metabolism test. Some estrogen derivates depend on comt which in turn depends on SAMe to deliver methyl groups.)

Lots of amino acids came back normal in the testing, most of the amino acids which were below the reference range need methionine/SAMe.
The other amino acids being low were phenylalanine, tyrosine, BCAAs, glutamic acid and aspartic acid.

Seems like an imbalance as glutathione uses up most of the methionine?

Other reasons for low methylation activity via SAMe could be lack of ATP and magnesium (it's needed by the enzyme). I am taking magnesium frequently and I guess my ATP levels are not so bad.

So beside the guess that most of the methionine is used up for glutathione synthesis I really don't know why I have this low methylation activity.

Any suggestions?

 

[PeterPositive]

That's right, could be much lower.
But why is it then that I am also low in substances depending on methionine/SAMe except glutathione?

Yes that sounds strange, at least at a first glance.
SAMe is used for GSH production, so a low SAMe typically goes hand in hand with a low GSH, unless you add GSH via supplementation (especially IV).

I've done a methylation panel and have seen another 4-5 test results from other users in this board... they definitely look very similar, with a recurring pattern of low SAMe/GSH and elevated GSSG and SAH.

Your case seems peculiar in these regards...

Seems like an imbalance as glutathione uses up most of the methionine?

I am not an expert, so it would be best to ask the lab that did the test for some advice or better interpretation of the (apparently) contradictory values.

Another thing is that... those methylation diagrams are a cool model to understand how things work in the cells but a full blown organism has so many freaking variables, so it's not that simple...

I think labs can provide a picture of what might be going on but they don't necessarily tell you the full story. I have fixed many of the bad values from my labs in the past 4-5 years but the great improvement in those numbers did not map to similar improvements in health ... although I did have some improvement.

So beside the guess that most of the methionine is used up for glutathione synthesis I really don't know why I have this low methylation activity.

There can be many reasons that go beyond the basics. Methylation blocks can be caused by heavy metal burden, chronic infections, lack of cofactors, enzyme impairment... etc...

Best thing would be to speak with a doctor with expertise in this field.

cheers

 

[Hope78]

Thanks for your reply. Will talk to an expert about this tomorrow. I will report about it!

 

[Kimsie]

Hello Hope78. We used to be on a vegan diet for years, with plenty of vegetable protein, and eventually we ran into problems from low methionine. I bet your low values are simply due to low methionine intake. Try eating some meat every day. Chicken is fine if that is what you wish to eat. The increase in methionine in your diet should increase your SAMe. You probably already get a lot of folate in your diet, but you may need B12.

Have you checked your zinc levels? Leaky gut can be caused by low zinc and your diet is probably not too high in zinc unless you have been supplementing.

 

[Hope78]

Hi Kimsie,
thanks for your input. I will increase my meat intake (even though I don't like meat so much). My B12 levels are fine, never the less I am supplementing small amounts auf methylB12 daily. I am also taking some zink every morning. My serum levels are fine, but I am low in intracellular zink