Pyruvate Carboxylase Deficiency

[wmackowiak]

Hello everyone,

I have a question regarding pyruvate carboxylase deficiency. Namely, I'd like to know which of the aminoacids is most likely to provide glucose production? I'm arguing with my friends about it. One of them says it's alanine but for me that's the one aminoacid that cannot be transformed to oxaloacetate from pyruvate... What do you think? Other ideas were Phenyloalanine, Valine, Arginine and LEucine (but this one is not glucogenic so I would odd this out) I'm really looking forward to hearing some professional voices  

[BabcockHall]

"Most likely" is an odd choice of terms.  Amino acids are classified as glucogenic (glycogenic), ketogenic, or both. Once anything is tranformed into pyruvate, I don't see what would prevent its further conversion.  Therefore, I don't know what you mean by "...cannot be transformed from oxaloacetate to pyruvate."  Can you explain?  Can alanine be transformed into pyruvate?  Once you have the answer to that, you will be on your way.  BTW your title is a bit confusing.  If there is a deficiency in this enzyme or in its allosteric activator, gluconeogenesis is likely to be impaired.  I am not sure that I see the connection between that and the question of how the amino acids are glycogenic.  Are you attempting to distinguish between those that are catabolized to pyruvate versus those that are catabolized to oxaloacetate?

Edited February 27, 2018 by BabcockHall
added last four sentences

[wmackowiak]

In Harper's biochemistry there is a sketch of "amphibolic intermediate products made of aminoacids' carbonic backbone". It shows through which different products aminoacids (not per se) are entering citric acid cycle.  

5 hours ago, BabcockHall said:

Therefore, I don't know what you mean by "...cannot be transformed from oxaloacetate to pyruvate."  Can you explain?  

In case of pyruvate carboxylase deficiency the conversion of pyruvate INTO oxaloacetate is impaired. 

Therefore, as I understand correctly, all aminoacids, which enter citric acid cycle through pyruvate, would not be used in the process of gluconeogenesis. Of course the whole process would be impaired but for instance Phenyloalanine is entering the citric acid cycle through fumarate. That would mean that there is no need for conversion into oxaloacetate by pyruvate carboxylase but by fumarate and malate dehydrogenase. 

I don't know if this question makes a lot of sense; it's quite complex and we wanted to take a look from different topics.

[BabcockHall]

What I would do is look into which amino acids are catabolized into 4-carbon TCA intermediates such as fumarate, oxaloacetate, or succinyl CoA versus which ones are catabolized into pyruvate.  For example, isoleucine is catabolized into acetyl CoA and propionyl CoA, and the latter compound can be converted into succinyl CoA in several steps.