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Functional and Pathological Roles of AHCY

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Specialty Cell Biology
Date 2021 Apr 19
PMID 33869213
Citations 22
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Abstract

Adenosylhomocysteinase (AHCY) is a unique enzyme and one of the most conserved proteins in living organisms. AHCY catalyzes the reversible break of -adenosylhomocysteine (SAH), the by-product and a potent inhibitor of methyltransferases activity. In mammals, AHCY is the only enzyme capable of performing this reaction. Controlled subcellular localization of AHCY is believed to facilitate local transmethylation reactions, by removing excess of SAH. Accordingly, AHCY is recruited to chromatin during replication and active transcription, correlating with increasing demands for DNA, RNA, and histone methylation. AHCY deletion is embryonic lethal in many organisms (from plants to mammals). In humans, AHCY deficiency is associated with an incurable rare recessive disorder in methionine metabolism. In this review, we focus on the AHCY protein from an evolutionary, biochemical, and functional point of view, and we discuss the most recent, relevant, and controversial contributions to the study of this enzyme.

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References
1.
Zhao J, Wang Y, Zhao B, Chen L . Analyzing S-adenosylhomocysteine hydrolase gene sequences in deuterostome genomes. J Biomol Struct Dyn. 2009; 27(3):371-80. DOI: 10.1080/07391102.2009.10507323. View

2.
Baric I, Cuk M, Fumic K, Vugrek O, Allen R, Glenn B . S-Adenosylhomocysteine hydrolase deficiency: a second patient, the younger brother of the index patient, and outcomes during therapy. J Inherit Metab Dis. 2006; 28(6):885-902. PMC: 2441944. DOI: 10.1007/s10545-005-0192-9. View

3.
Westermann F, Muth D, Benner A, Bauer T, Henrich K, Oberthuer A . Distinct transcriptional MYCN/c-MYC activities are associated with spontaneous regression or malignant progression in neuroblastomas. Genome Biol. 2008; 9(10):R150. PMC: 2760877. DOI: 10.1186/gb-2008-9-10-r150. View

4.
Masuta C, Tanaka H, Uehara K, Kuwata S, Koiwai A, Noma M . Broad resistance to plant viruses in transgenic plants conferred by antisense inhibition of a host gene essential in S-adenosylmethionine-dependent transmethylation reactions. Proc Natl Acad Sci U S A. 1995; 92(13):6117-21. PMC: 41653. DOI: 10.1073/pnas.92.13.6117. View

5.
Kent W . BLAT--the BLAST-like alignment tool. Genome Res. 2002; 12(4):656-64. PMC: 187518. DOI: 10.1101/gr.229202. View