FA pg 109

[super87]

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I have brain fog.

Under Homocystinuria, in the case of cystathione synthase deficiency, why does it say treatment includes increased B12 and folate in diet? It seems that those would pull the reaction backwards towards methionine and the problem here is that the pt is not making enough cysteine.

Halp.

 

[Goober11]

I think the point of giving B12 at least is to just make sure the body gets rid of homocysteine.Yes, they are making methionine (it's intake the patient will have to restrict), not cysteine. However, homocysteine itself is very toxic and is the substance behind the strokes and MIs that are commonly seen in kiddos with homocystinuria (endothelial damage-->coag cascade).

It is much easier to manage a kid by telling them "no methionine" than it is to let their CV system get ravaged by homocysteine.

I have no idea why you would give folate. My guess would be that it aids in making methionine thus removing even more homocysteine.

 

[Jonari]

I think the point of giving B12 at least is to just make sure the body gets rid of homocysteine.Yes, they are making methionine (it's intake the patient will have to restrict), not cysteine. However, homocysteine itself is very toxic and is the substance behind the strokes and MIs that are commonly seen in kiddos with homocystinuria (endothelial damage-->coag cascade).

It is much easier to manage a kid by telling them "no methionine" than it is to let their CV system get ravaged by homocysteine.

I have no idea why you would give folate. My guess would be that it aids in making methionine thus removing even more homocysteine.

yup, it's the lesser of two evils, even though it'll just be recycled back to homocysteine, it's still better than having it in circulation. it's the same thing with the job of HDL...picks up oxidized-LDL brings it to the liver, but it still gets recirculated...you're just removing it from the system.

you give folate, because that enzyme "homocysteine methyltransferase" requires two coenzymes/cofactors...the coenzyme form of vb12 ka adenosine-cobalamin or methylcobalamin and methylTHF to work...see attachment of picture from kap biochem...disregard the notes

 

[super87]

Thanks you two! 🙂

 

[Zzmed]

The problem in Homocystinuria is not making less cysteine. Its increased homocysteine (for the reasons the guys said).

And the reason for why giving folate is in FA under Vit B12 (diagram). No need to check Kaplan (no offense Jonari!)

PLUS, I may be wrong, but, I don't know of a disease due to excess of methionine. So why not get the reactions "backwards" to methionine? I mean, methionine is for giving CH3 for anabolic reactions, right?

 

[CaptainSSO]

Yea, IIRC there's only 2 rxns with B12: homocysteine --> methionine and methylmalonyl CoA to succinyl CoA. The first requires folate and the second doesn't, which is why subacute combined degeneration doesn't arise from folate deficiency.

 

[Zzmed]

PLUS, I may be wrong, but, I don't know of a disease due to excess of methionine. So why not get the reactions "backwards" to methionine? I mean, methionine is for giving CH3 for anabolic reactions, right?

Guys, any thoughts on this?

 

[as90]

sorry to drag up an old thread, but why are you restricting methionine in homocystinuria?

is it because now that you are giving them B12, you are going to be having a lot of methionine via the homocystine methyltransferase which gets rid of the homocysteine, but will give u too much methionine?

 

[xeroun]

sorry to drag up an old thread, but why are you restricting methionine in homocystinuria?

is it because now that you are giving them B12, you are going to be having a lot of methionine via the homocystine methyltransferase which gets rid of the homocysteine, but will give u too much methionine?

I thought so too but apparently its a way more awesome reason than that.
Let see if I can explain this to make sense:
Homocysteine methyl transferase activity is dependent on BOTH the Cofactor (B12) and the Product (Methionine)

They affect the enzyme activity by two different mechanisms. B12 stabilizes the enzyme and keeps it from being degraded too quickly.
Methionine actually affects the synthesis of Homocysteine methyl transferase.

Low Methionine levels --> Increased Synthesis of Homocystine methyl transferase . Increased B12 ---> Homocysteine methyl transferase Stays around longer.

increase B12 without decreasing Methionine: Enzyme activity increases 4-fold
increase B12 And decrease Methionine: Enzyme activity increases 4-fold from B12 plus an additional 2-4fold increase (8-16 fold)

So in summary decreasing Methionine is for the enzyme to work better to get rid of Homocysteine.

Sources: Proc Natl Acad Sci U S A. 1973 September; 70(9): 2585–2589.

 

[sharklasers]

sorry to drag up an old thread, but why are you restricting methionine in homocystinuria?

is it because now that you are giving them B12, you are going to be having a lot of methionine via the homocystine methyltransferase which gets rid of the homocysteine, but will give u too much methionine?

The above explanation looks very thorough and is probably right (too long lol), but the way I thought about it was considering that methionine can be converted back to homocysteine via some enzyme and SAM. To much methionine would mean some would get converted to homocysteine, worsening the problem of already high homocysteine.

 

[as90]

thanks so much!