Carnitine supplementation in methylmalonic and propionic acidemia

[loveoforganic]

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A source says carnitine supplementation improves these acidemias by improving B-oxidation of fatty acids. How is the beneficial in most people? Unless B-oxidation rates in the normal population are generally limited by low [carnitine]? I assume the idea is you want to shift away from protein digestion, you're still going to have (accelerated, supposedly) degradation of odd chain FAs to propionioc acid

 

[lemonade90]

A source says carnitine supplementation improves these acidemias by improving B-oxidation of fatty acids. How is the beneficial in most people? Unless B-oxidation rates in the normal population are generally limited by low [carnitine]? I assume the idea is you want to shift away from protein digestion, you're still going to have (accelerated, supposedly) degradation of odd chain FAs to propionioc acid

I don't know why it would be beneficial but Carnitine is a key component for the rate limiting enzyme for fatty acid oxidation (carnitine acyltransferase I) so you would be impacting enzyme kinetics by allowing more enzyme to act on more substrate at the same time.

 

[Phloston]

I don't know why it would be beneficial but Carnitine is a key component for the rate limiting enzyme for fatty acid oxidation (carnitine acyltransferase I) so you would be impacting enzyme kinetics by allowing more enzyme to act on more substrate at the same time.

If you turn to p. 101 of FA2012, the rate-limiting enzyme for fatty acid oxidation is carnitine acyltransferase I (CAT-I).

Therefore, fatty acid oxidation is a zero-order reaction (enzyme-limited) dependent on CAT-I, and increasing [CAT-I] would increase Vmax.

Lemonade already nailed it.

 

[loveoforganic]

I'm ok with that, assuming CAT-I isn't normally close to saturation with carnitine. How does this improve the acidemias though? Is it the protein sparing effect? I suppose this would make more sense if it was a treatment for the acidemias in infants, who would be on high fat/protein diets. I assume increased propionic acid due to increased odd chain FA metabolism would be more than offset by less branched chain AA metabolism?

 

[Phloston]

Loveoforganic, I'm not 100% sure what you're asking. Could you please elaborate?

 

[loveoforganic]

Metabolism of certain proteins (branched chain as well as a couple others I don't remember offhand) and B-oxidation of odd chain fatty acids will lead to 1) propionyl-CoA and thus propionic acid in those deficient in propionyl-CoA carboxylase or 2) methylmalonyl-CoA and thus methylmalonic acid in those deficient in B12/methylmalonyl-CoA mutase.

I assume by improving B-oxidation, your goal is to shift metabolism from protein to fatty acid. However, there are plenty of fats (all odd-chain fats) that will lead to the same problems as the amino acid metabolism. I assume that there just must be less of a buildup due to odd-chain fatty acid degradation than amino acid degradation, otherwise I don't understand the utility of the treatment. Is this correct, or am I missing something? If I'm still being unclear let me know