Biyotinidaz eksikliğinin plazma kolinesteraz aktivitesi üzerindeki etkilerinin araştırılması

Öz

Amaç: Biotinidaz eksikliği (BD), vücudun çeşitli metabolik süreçlerde yer alan karboksilaz enzimleri için kritik bir koenzim olan biotini geri dönüştürme yeteneğini bozan nadir bir otozomal resesif metabolik bozukluktur. Bu çalışma, yetersiz biotin geri dönüşümünün neden olduğu metabolik bozulmaların kolinesteraz fonksiyonunda değişikliklere yol açabileceği hipotezini test ederek, biotinidaz eksikliğinin plazmadaki kolinesteraz aktivitesi üzerindeki etkilerini değerlendirmeyi amaçlamaktadır. Gereç ve yöntem: Plazma örnekleri, yabanıl tip (n=12), heterozigot (n=30), homozigot (n=19) ve bileşik heterozigot (n=12) olarak kategorize edilen 73 bireyden toplandı. Kolinesteraz aktivitesi kolorimetrik bir yöntem kullanılarak ölçüldü. Bulgular: Bu çalışmada, heterozigot grubun kolinesteraz aktivitesinin homozigot gruptan daha yüksek olduğu bulundu (p=0,0356). Ek olarak, yabanıl tip ve heterozigot gruplarına kıyasla homozigot ve bileşik heterozigot bireylerde kolinesteraz aktivitesinin önemli ölçüde azaldığı bulundu (p=0,0272). Farklılıklar istatistiksel olarak anlamlıydı ve bu durum, biotinidaz eksikliği ile değişmiş kolinerjik fonksiyon arasında potansiyel bir bağlantıyı işaret etmektedir. Sonuç: Bulgular, özellikle ciddi formlarında biotinidaz eksikliğinin, kolinesteraz aktivitesinde önemli azalmalarla sonuçlanabileceğini ve bu durumun etkilenen bireylerde gözlemlenen nörolojik semptomlara katkıda bulunabileceğini düşündürmektedir. Bu ilişkiyi açıklamak ve BD'nin kolinesteraz aktivitesi ve nörolojik sağlık üzerindeki etkilerini hafifletmeye yönelik terapötik stratejiler geliştirmek için daha fazla araştırmaya ihtiyaç vardır.

Anahtar Kelimeler

• Biyotinidaz eksikliği
• kolinesteraz
• metabolik bozukluk

Investigation of the effects of biotinidase deficiency on plasma cholinesterase activity

Öz

Purpose: Biotinidase deficiency (BD) is a rare autosomal recessive metabolic disorder that impairs the body's ability to recycle biotin, a crucial coenzyme for carboxylase enzymes involved in various metabolic processes. This study aims to evaluate the effects of biotinidase deficiency on cholinesterase activity in plasma, hypothesizing that the metabolic disruptions caused by inadequate biotin recycling may lead to alterations in cholinesterase function. Materials and methods: Plasma samples were collected from 73 individuals categorized into four genetic groups: wild type (n=12), heterozygous (n=30), homozygous (n=19), and compound heterozygous (n=12). Cholinesterase activity was measured using a colorimetric method. Results: The study discovered that the cholinesterase activity of the Heterozygous group was higher than the homozygous group (p=0.0356). Additionally, cholinesterase activity was significantly lower in homozygous and compound heterozygous people than in wild and heterozygous groups (p=0.0272). The statistically significant changes suggested a relationship between biotinidase deficiency and altered cholinergic activity. Conclusion: The findings indicate that biotinidase deficiency, particularly in its severe variants, may cause considerable reductions in cholinesterase activity, contributing to the neurological symptoms found in affected patients. More studies are needed to investigate the processes behind this association and develop strategies for reducing the effects of BD on cholinesterase activity and neurological health.

Anahtar Kelimeler

• Biotinidase deficiency
• cholinesterase
• metabolic disorder

Kaynakça

1. Wolf B. Clinical issues and frequent questions about biotinidase deficiency. Mol Genet Metab. 2010;100(1):6-13. doi.org/10.1016/j.ymgme.2010.01.003
2. Silman I. The multiple biological roles of the cholinesterases. Prog Biophys Mol Biol. 2021;162:41-56. doi.org/10.1016/j.pbiomolbio.2020.12.001
3. Soreq H, Podoly E, Gok M. Cholinesterases. Encyclopedia of Molecular Pharmacology. 2020:1-8. doi.org/10.1007/978-3-030-21573-6_184-1
4. Gok M, Cicek C, Bodur E. Butyrylcholinesterase in lipid metabolism: A new outlook. J Neurochem 2024;168(4):381-385. doi.org/10.1111/jnc.15833
5. García Ayllón MS, Cauli O, Silveyra MX, et al. Brain cholinergic impairment in liver failure. Brain. 2008;131(11):2946-2956. doi.org/10.1093/brain/awn209
6. Hosoi M, Hori K, Konishi K, et al. Plasma cholinesterase activity in Alzheimer's disease. Neurodegener Dis. 2015;15(3):188-190. doi.org/10.1159/000381532
7. Villeda González JD, Gómez Olivares JL, Baiza Gutman LA. New paradigms in the study of the cholinergic system and metabolic diseases: Acetyl‐and‐butyrylcholinesterase. J Cell Physiol 2024;239:e31274 doi.org/10.1002/jcp.31274
8. Ercan M, Akbulut ED, Oz O, Ataş N, Karaca M, Yılmaz FM. Evaluation of the efficiency of serum biotinidase activity as a newborn screening test in Turkey. J Pediatr Endocrinol Metab. 2020;34(1):89-94. Published 2020 Nov 13. doi.org/10.1515/jpem-2020-0382

9. Gok M, Cicek C, Sari S, Bodur E. Novel activity of human BChE: Lipid hydrolysis. Biochimie. 2023;204:127-135. doi.org/10.1016/j.biochi.2022.09.008
10. Martinelli I, Tomassoni D, Moruzzi M, Traini E, Amenta F, Khosrow Tayebati S. Obesity and metabolic syndrome affect the cholinergic transmission a nd cognitive functions. CNS Neurol Disord Drug Targets. 2017;16(6):664-676. doi.org/10.2174/1871527316666170428123853
11. Wolf B. Biotinidase deficiency: if you have to have an inherited metabolic disease, this is the one to have. Genet Med. 2012;14(6):565-575. doi.org/10.1038/gim.2011.6
12. Mishra P, Pandey CM, Singh U, Gupta A, Sahu C, Keshri A. Descriptive statistics and normality tests for statistical data. Ann Card Anaesth. 2019;22(1):67-72. doi.org/10.4103/aca.ACA_157_18
13. Strovel ET, Cowan TM, Scott AI, Wolf B. Laboratory diagnosis of biotinidase deficiency, 2017 update: a technical standard and guideline of the American College of Medical Genetics and Genomics [published correction appears in Genet Med. 2018 Feb;20(2):282. doi: 10.1038/gim.2017.201] [published correction appears in Genet Med. 2023 Jan;25(1):164-165. doi: 10.1016/j.gim.2022.11.014]. Genet Med. 2017;19(10):10.1038/gim.2017.84. doi:10.1038/gim.2017.84
14. Haake A, Nguyen K, Friedman L, Chakkamparambil B, Grossberg GT. An update on the utility and safety of cholinesterase inhibitors for the treatment of Alzheimer’s disease. Expert Opin Drug Saf. 2020;19(2):147-157. doi.org/10.1080/14740338.2020.1721456
15. Kaduszkiewicz H, Zimmermann T, Beck Bornholdt HP, van den Bussche H. Cholinesterase inhibitors for patients with Alzheimer's disease: systematic review of randomised clinical trials. BMJ. 2005;331(7512):321-327. doi.org/10.1136/bmj.331.7512.321
16. Chang EH, Chavan SS, Pavlov VA. Cholinergic Control of Inflammation, Metabolic Dysfunction, and Cognitive Impairment in Obesity-Associated Disorders: Mechanisms and Novel Therapeutic Opportunities. Front Neurosci. 2019;13:263. Published 2019 Apr 5. doi:10.3389/fnins.2019.00263
17. Majhi S, Kumar S, Singh L. A Review on Autism Spectrum Disorder: Pathogenesis, Biomarkers, Pharmacological and Non-Pharmacological Interventions. CNS Neurol Disord Drug Targets. 2023;22(5):659-677. doi:10.2174/1871527321666220428134802
18. Alcântara VM, Oliveira LC, Réa RR, Suplicy HL, Chautard-Freire-Maia EA. Butyrylcholinesterase activity and metabolic syndrome in obese patients. Clin Chem Lab Med. 2005;43(3):285-288. doi:10.1515/CCLM.2005.048
19. Furtado Alle L, Tureck LV, de Oliveira CS, Hortega JV, Souza RL. Butyrylcholinesterase and lipid metabolism: Possible dual role in metabolic disorders. Chem Biol Interact. 2023;383:110680. doi.org/10.1016/j.cbi.2023.110680
20. Sridhar GR, Rao AA, Srinivas K, et al. Butyrylcholinesterase in metabolic syndrome. Med Hypotheses. 2010;75(6):648-651. doi.org/10.1016/j.mehy.2010.08.008