Methylmalonic Acid (MMA) is a marker of vitamin B12 deficiency. High levels of MMA can indicate a deficiency of vitamin B12, which can cause anemia and neurological problems.
Isoleucine, like valine, is metabolized to propionyl-CoA and methylmalonyl-CoA. Elevated isoleucine can occur alongside increased MMA when this pathway is disrupted.
Berry, L. E., et al.. Impact on Isoleucine and Valine Supplementation When Decreasing Use of Medical Food in the Nutritional Management of Associated Disorders. Nutrients (2020). https://www.mdpi.com/2072-6643/12/2/473
Methionine is a precursor to S-adenosylmethionine, a key methyl donor required for the conversion of methylmalonyl-CoA to succinyl-CoA. Impaired methionine metabolism can contribute to MMA accumulation.
Propionylcarnitine is derived from propionyl-CoA, a precursor of methylmalonyl-CoA in the metabolic pathway that leads to MMA formation. Elevated propionylcarnitine is a strong indicator of a block in this pathway causing MMA buildup.
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Succinic acid is formed from succinyl-CoA, the product of the methylmalonyl-CoA pathway. Decreased succinic acid may be observed when the pathway is blocked, causing elevated MMA.
S. Verbeke, E. De Roo, E. Van Puyvelde, et al.. “Serum methylmalonic acid concentrations at breast cancer diagnosis and their association with clinical frailty and survival in older patients”. European Journal of Cancer (2023). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10828366/
Valine is metabolized to propionyl-CoA and subsequently methylmalonyl-CoA. Impairment in the methylmalonyl-CoA pathway can lead to both elevated valine and MMA levels.
S. Kruger, M. L. Brusius, A. R. Hoffmann, H. A. Grünert, and J. Kohlmüller. Isolated methylmalonic acidemias (MMA) - PMC - NCBI. Medical foods for methylmalonic and propionic acidemias (MMA/PA) contain minimal valine, isoleucine, methionine and threonine, but have been used in MMA/PA treatment for decades. (2016). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752925/
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J. A. D. M. van der Walt, M. A. van Kuilenburg, M. C. J. van Rij, and J. M. A. Boon. Methylmalonic acid, vitamin B12, renal function, and risk of all-cause mortality. PLOS ONE (2020). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726887/