Why are ketogenic aminoacids given in Pyruvate Dehydrogenase Deficiency?

Answer 1

Extremely rare disease. Good question. ketogenic diet which is low in carbohydrates and high in fats and protein often recommended. Thus Fatty acids are preferentially used for fuel instead of glucose, which reduces the amount of pyruvate, which subsequently reduces the amount of lactic acid, which is present in excess in these individuals and is one of the chief factors worsening their disease. Proven effects of this are lacking, Particularly in severe cases but it is definitely worth trying. (for a more detailed explanation of Patho physiology review glycolysis and pyruvate entering Krab cycle and ATP generation etc.) Thank You!

Answer 2

Hey

Amber did a great job in explaining the basic idea behind giving ketogenic amino acids to PDD patients. The other component of treatment is a lipid rich and low carb diet to prevent lactic acidosis.

But to add to the previous explanation, just look at the image below. In PDD, Pyruvate is not transformed to Acetyl-CoA. So purely ketogenic amino acids are Lysine and Leucine are good options but note that there are other options as well. However, the ketogenic ones are the classic.

https://upload.wikimedia.org/wikipedia/commons/1/16/Amino_acid_catabolism_revised.png

Answer 3

Ketogenic amino acids (such as lysine/leucine - the treatment for PD deficiency) break down into acetyl-CoA which can enter the TCA cycle). Other amino acids are glucogenic, which means they would potentially break down into glucose which would undergo glycolysis → pyruvate which can’t be broken down by PDH because it is deficient.

Thus ketogenic aa's are the treatment of PD deficiency because they allow the TCA cycle to still function (supplies the majority of the "fuel" aka NADPH, FADH, ATP for the electron transport chain to make energy (ATP)) without causing back up of pyruvate and alanine which can become toxic (→lactate → lactic acidosis).

Hope that makes sense!