Propiyonat Metabolizması Bozukluklarında Kullanılan Tıbbi Formülaların Lösin İçeriğinin Tedavi Üzerine Etkisi

Yıl 2025, Cilt: 14 Sayı: 1, 43 - 51, 25.06.2025

Furkan Yolcu , Gülhan Samur

https://doi.org/10.46971/ausbid.1690707

Öz

Lösin, insan vücudunda birçok önemli etkiye sahip metabolik bir düzenleyicidir. Propiyonat metabolizma bozukluğu olan hastalarda kullanılan tıbbi formülalar propiyojenik amino asitleri içermezken lösin amino asidini fazla miktarda içermektedir. Yapılan çalışmalar, metilmalonik asidemi ve propiyonik asidemili hasta grubunda kullanılan tıbbi formüla içeriğinden gelen lösin alımının hastalarda beklenmeyen yan etkilere yol açabileceğini göstermiştir. Propiyonat metabolizması bozukluğunun tıbbi beslenme tedavisinde doğal protein alımının sınırlandırılması ve tıbbi formüla kullanım miktarının artması sonucunda, tıbbi formüladan gelen yüksek miktarda lösin alımına bağlı lösin/valin ve/veya lösin/izolösin oranlarında dengesizlikle sonuçlanır. Bu durum esansiyel amino asitlerden olan valin ve izolösinin plazma seviyelerinin düşük olmasına neden olur. Plazmada yüksek düzeyde bulunan lösin kan-beyin bariyeri boyunca metioninin de taşınmasının azalmasına, endojen metionin sentezinin bozulduğu kobalamin C defektinde de özellikle endişe vericidir. Bu derlemenin amacı lösin açısından zengin ve propiyojenik amino asitleri içermeyen hastalığa özgü tıbbi formülanın, metilmalonik asidemi, propiyonik asidemi ve kobalamin C defektinin beslenme yönetimindeki olası etkilerine dikkat çekerek diyet önerileri geliştirmektir. Metilmalonik asidemi ve propiyonik asidemide kullanılan tıbbi formülaların en uygun amino asit bileşimi üzerine araştırmalara ihtiyaç vardır. Uygun içerik oluşturulana kadar, metilmalonik asidemi ve propiyonik asidemide tıbbi formülalar beslenme yönetiminde dikkatli bir şekilde kullanılmalı ve kobalamin C defektinde ise hastalığa özgü olan tıbbi formülalar kullanılmamalıdır.

Anahtar Kelimeler

Metilmalonik asidemi , propiyonik asidemi , kobalamin c defekti

Effect of Leucine Content of Medical Foods Used in Propionate Metabolism Disorders on Treatment

Öz

Leucine is a metabolic regulator with numerous important functions in the human body. Medical formulas used in patients with propionate metabolism disorders are devoid of propiogenic amino acids but contain disproportionately high amounts of leucine. Studies have indicated that the elevated leucine intake from these medical formulas may lead to unexpected adverse effects in patients with methylmalonic acidemia (MMA) and propionic acidemia (PA). In the dietary management of propionate metabolism disorders, restriction of natural protein intake and increased dependence on medical formulas often result in imbalanced leucine/valine and/or leucine/isoleucine ratios due to the excessive leucine content of these formulas. This imbalance can lead to decreased plasma levels of the essential amino acids valine and isoleucine. Additionally, elevated plasma leucine may reduce the transport of methionine across the blood–brain barrier, which is particularly concerning in cobalamin C (cblC) deficiency, where endogenous methionine synthesis is already impaired. The aim of this review is to draw attention to the potential nutritional implications of disease-specific medical formulas that are rich in leucine and free from propiogenic amino acids in the management of MMA, PA, and cblC deficiency, and to improve dietary recommendations. There is a clear need for further research to determine the optimal amino acid composition of medical formulas used in MMA and PA. Until such formulations are developed, the use of medical formulas should be approached with caution in the dietary management of MMA and PA, and disease-specific medical formulas should be avoided in patients with cobalamin C deficiency.

Anahtar Kelimeler

Methylmalonic acidemia , propionic acidemia , cobalamin c deficiency

Kaynakça

• Ahrens-Nicklas, R. C., Whitaker, A. M., Kaplan, P., Cuddapah, S., Burfield, J., Blair, J., et al. (2017). Efficacy of early treatment in patients with cobalamin C disease identified by newborn screening: A 16-year experience. Genetics in Medicine, 19(8), 926–935. https://doi.org/10.1038/gim.2016.214
• Baumgartner, M. R., Hörster, F., Dionisi-Vici, C., Haliloglu, G., Karall, D., Chapman, K. A., et al. (2014). Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia. Orphanet Journal of Rare Diseases, 9(1), 130. https://doi.org/10.1186/s13023-014-0130-8
• Bifari, F., & Nisoli, E. (2017). Branched‐chain amino acids differently modulate catabolic and anabolic states in mammals: A pharmacological point of view. British Journal of Pharmacology, 174(11), 1366–1377. https://doi.org/10.1111/bph.13624
• Elango, R., Rasmussen, B., & Madden, K. (2016). Safety and tolerability of leucine supplementation in elderly men. The Journal of Nutrition, 146(12), 2630S–2634S. https://doi.org/10.3945/jn.116.234930
• Evans, M., Truby, H., & Boneh, A. (2017). The relationship between dietary intake, growth, and body composition in inborn errors of intermediary protein metabolism. The Journal of Pediatrics, 188, 163–172. https://doi.org/10.1016/j.jpeds.2017.05.048
• Gao, X., Tian, F., Wang, X., Zhao, J., Wan, X., Zhang, L., et al. (2015). Leucine supplementation improves acquired growth hormone resistance in rats with protein-energy malnutrition. PLOS ONE, 10(4), e0125023. https://doi.org/10.1371/journal.pone.0125023
• Heeley, N., & Blouet, C. (2016). Central amino acid sensing in the control of feeding behavior. Frontiers in Endocrinology, 7, 148. https://doi.org/10.3389/fendo.2016.00148
• Holecek, M., Siman, P., Vodenicarovova, M., & Kandar, R. (2016). Alterations in protein and amino acid metabolism in rats fed a branched-chain amino acid- or leucine-enriched diet during postprandial and postabsorptive states. Nutrition & Metabolism, 13(1), 12. https://doi.org/10.1186/s12986-016-0072-3
• Huemer, M., Diodato, D., Schwahn, B., Schiff, M., Bandeira, A., Benoist, J.-F., et al. (2017). Guidelines for diagnosis and management of the cobalamin-related remethylation disorders cblC, cblD, cblE, cblF, cblG, cblJ and MTHFR deficiency. Journal of Inherited Metabolic Disease, 40(1), 21–48. https://doi.org/10.1007/s10545-016-9991-4
• Manoli, I., Myles, J. G., Sloan, J. L., Shchelochkov, O. A., & Venditti, C. P. (2016). A critical reappraisal of dietary practices in methylmalonic acidemia raises concerns about the safety of medical foods. Part 1: Isolated methylmalonic acidemias. Genetics in Medicine, 18(4), 386–395. https://doi.org/10.1038/gim.2015.102
• Matsumoto, T., Nakamura, K., Matsumoto, H., Sakai, R., Kuwahara, T., Kadota, Y., et al. (2014). Bolus ingestion of individual branched-chain amino acids alters plasma amino acid profiles in young healthy men. SpringerPlus, 3, 35. https://doi.org/10.1186/2193-1801-3-35
• Myles, J. G., Manoli, I., & Venditti, C. P. (2018). Effects of medical food leucine content in the management of methylmalonic and propionic acidemias. Current Opinion in Clinical Nutrition and Metabolic Care, 21(1), 42. https://doi.org/10.1097/MCO.00000000000000428
• Saudubray, J. M., & Garcia-Cazorla, À. (2018). Inborn errors of metabolism overview: Pathophysiology, manifestations, evaluation, and management. Pediatric Clinics of North America, 65(1), 179–208. https://doi.org/10.1016/j.pcl.2017.09.008
• Scaglia, F. (2014). Inborn errors of metabolism: From neonatal screening to metabolic pathways (p. 92). Oxford University Press. https://doi.org/10.1093/med/9780199797585.001.0001
• Shchelochkov, O. A., Carrillo, N., & Venditti, C. (2016). Propionic acidemia. In M. P. Adam, H. H. Ardinger, R. A. Pagon, et al. (Eds.), GeneReviews® (Updated October 6, 2016). University of Washington, Seattle. https://pubmed.ncbi.nlm.nih.gov/22593918/
• Sperringer, J. E., Addington, A., & Hutson, S. M. (2017). Branched-chain amino acids and brain metabolism. Neurochemical Research, 42(6), 1697–1709. https://doi.org/10.1007/s11064-017-2261-5
• Su, W., Xu, W., Zhang, H., Ying, Z., Zhou, L., Zhang, L., et al. (2017). Effects of dietary leucine supplementation on the hepatic mitochondrial biogenesis and energy metabolism in normal birth weight and intrauterine growth-retarded weanling piglets. Nutrition Research and Practice, 11(2), 121–129. https://doi.org/10.4162/nrp.2017.11.2.121
• Wessels, A. G., Kluge, H., Hirche, F., Kiowski, A., Schutkowski, A., Corrent, E., et al. (2016). High leucine diets stimulate cerebral branched-chain amino acid degradation and modify serotonin and ketone body concentrations in a pig model. PLOS ONE, 11(3), e0150376. https://doi.org/10.1371/journal.pone.0150376
• Yokota, S.-I., Ando, M., Aoyama, S., Nakamura, K., & Shibata, S. (2016). Leucine restores murine hepatic triglyceride accumulation induced by a low-protein diet by suppressing autophagy and excessive endoplasmic reticulum stress. Amino Acids, 48(4), 1013–1021. https://doi.org/10.1007/s00726-015-2149-0
• Zhen, H., Kitaura, Y., Kadota, Y., Ishikawa, T., Kondo, Y., Xu, M., et al. (2016). mTORC1 is involved in the regulation of branched‐chain amino acid catabolism in mouse heart. FEBS Open Bio, 6(1), 43–49. https://doi.org/10.1002/2211-5463.12007
• Zhen, H., Nakamura, K., Kitaura, Y., Kadota, Y., Ishikawa, T., Kondo, Y., et al. (2015). Regulation of the plasma amino acid profile by leucine via the system L amino acid transporter. Bioscience, Biotechnology, and Biochemistry, 79(12), 2057–2062. https://doi.org/10.1080/09168451.2015.1060845