PDH deficiency and differential response to thiamine

[docmira]

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Hi,
I was wondering why some people with PDH deficiency respond to doses of thiamine while others do not. I have found on the web that alcoholism, HIV, and other diseases play a role, but i'm looking for more of a biochemical explanation.
Can anyone help me.
Thanks!

 

[fielight]

not sure if this is what you are looking for, but as i understand it, pyruvate dehydrogenase requires thiamin as a cofactor (in the rxn: pyruvate + CoASH --> acetyl CoA). alcoholism affects the enzyme, because alcohol interferes with the mucosa lining of the stomach and decreases thiamin absorption. accordingly, this deficiency will decrease TCA output (thiamin is also required for a-ketoglutarate dehydrogenase, also in TCA). i have no idea how HIV affects this though... in amino acid metabolism, transamination rxns also requires pyridoxal phosphate as a cofactor (which is related to thiamin). certainly, this could also affect aa degradation...

 

[docmira]

thanks for your response!
I am looking for the reason why some respond to the thiamine treatments and some do not.
I am not sure what effects alcoholism etc has, but I don't think it's relevant to this situation.
So if thiamine doesn't bind, does that affect the rest of the PDH cycle?
Anyone know why some people don't respond to the treatments?
I appreciate the help..this question is really bothering me!

 

[Entol]

Alcoholism has this effect:

if youre an alcoholic, youre taking in most of your calories from alcohol, so you're ignoring other important foods that have thiamine in them. Therefore, this can lead to a thiamine defiency. I'm pretty sure it's that simple. 🙂

thanks for your response!
I am looking for the reason why some respond to the thiamine treatments and some do not.
I am not sure what effects alcoholism etc has, but I don't think it's relevant to this situation.
So if thiamine doesn't bind, does that affect the rest of the PDH cycle?
Anyone know why some people don't respond to the treatments?
I appreciate the help..this question is really bothering me!

 

[docmira]

thanks again
But like i said..the alcohol isn't related here...as far as i know
Sorry i mentioned that in the first post. I was just using as an example of the useless things i found while googling.

I think this just has to do with the biochemistry of the pathways...but i can't figure it out 😕

 

[Entol]

Ohh i see what you're saying. Sorry, I misread your post.

Well here is my stab in the dark:
Some PDH deficiencies are genetic, which are not affected by intake of thiamine. Others are thiamine defiency PDH defiencies, like the alcoholism example or other malnutrition. These are due to the lack of a cofactor.

In a sense, the active enzyme requires two parts to work, a working PDH enzyme and a cofactor, thiamine. If thiamine is the missing part, infusion of thiamine into the blood will fix it. If the enzyme is the defective part, then no amount of thiamine will create an active, working enzyme.

thanks again
But like i said..the alcohol isn't related here...as far as i know
Sorry i mentioned that in the first post. I was just using as an example of the useless things i found while googling.

I think this just has to do with the biochemistry of the pathways...but i can't figure it out 😕

 

[SaltySqueegee]

The only other explanation for the lack of PDH function return after repleting Thiamine, is that other cofactors might be low, or excess (-)Regulators.

CoEnzymes of PDH:
Thiamine PyroPhosphate
Lipoic Acid
NAD
FAD
CoA

(-) Regulators of PDH:
ATP
NADH
Acetyl-CoA

With alcoholics and quite a few disease states there is an NAD deficiency due to used up metabolic pathways (alcohol dehydrogenase, etc.). This is most likely the reason why the return of Thiamine does not solve the problem always. Most likely another coenzyme is low/absent, in this case NAD, which prevents the Committed step for TCA from occuring. 👍

Regards,

-Salty

 

[SaltySqueegee]

POST #1,000!!!

WOOOHOOO!!!

... okay, I'm going to sleep now... it's a little too late... 😴

 

[Tiki]

As has already been mentioned, you need five cofactors during the reaction. The pyruvate dehydrogenase complex has three distinct regions that are involved in the reaction. The E1 part of the complex uses Thiamine whereas E2 and E3 require different cofactors.

So if someone had a defiency that affected the E2 or E3 part of the complex, giving Thiamine would not help them at all.

 

[thackl]

Don't forget methylomonic acidemia (not sure if I spelled it right)

 

[docmira]

THANKS GUYS 😀