Unveiling overlooked pathways: The uric acid catabolism genes in the human genome.

Autor: Rodrigues JT; Macromolecular Biophysics Laboratory (LBM), Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, 31270-901, Brazil., Mamede I; Biochemical Genetics Laboratory (LGB), Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, 31270-901, Brazil., Franco GR; Biochemical Genetics Laboratory (LGB), Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, 31270-901, Brazil., de Magalhães MTQ; Macromolecular Biophysics Laboratory (LBM), Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, 31270-901, Brazil. Electronic address: mquezado@icb.ufmg.br.
Jazyk: angličtina
Zdroj: Biochimie [Biochimie] 2024 Jun 25. Date of Electronic Publication: 2024 Jun 25.
DOI: 10.1016/j.biochi.2024.06.010
Abstrakt: In hominids, including Homo sapiens, uric acid is the end product of purine catabolism. In contrast, other placental mammals further degrade uric acid to (S)-allantoin by enzymes such as urate oxidase (uricase), HIU hydrolase (HIUase), and OHCU decarboxylase. Some organisms, such as frogs and fish, hydrolyze (S)-allantoin to allantoate and eventually to (S)-ureidoglycolate and urea, while marine invertebrates convert urea to ammonium. In H. sapiens, mutations in the uricase gene led to a reduction in the selective pressure for maintaining the integrity of the genes encoding the other enzymes of the purine catabolism pathway, resulting in an accumulation of uric acid. The hyperuricemia resulting from this accumulation is associated with gout, cardiovascular disease, diabetes, and preeclampsia. Many commonly used drugs, such as aspirin, can also increase uric acid levels. Despite the apparent absence of these enzymes in H. sapiens, there appears to be production of transcripts for uricase (UOX), HIUase (URAHP), OHCU decarboxylase (URAD), and allantoicase (ALLC). While some URAHP transcripts are classified as long non-coding RNAs (lncRNAs), URAD and ALLC produce protein-coding transcripts. Given the presence of these transcripts in various tissues, we hypothesized that they may play a role in the regulation of purine catabolism and the pathogenesis of diseases associated with hyperuricemia. Here, we specifically investigate the unique aspects of purine catabolism in H. sapiens, the effects mutations of the uricase gene, and the potential regulatory role of the corresponding transcripts. These findings open new avenues for research and therapeutic approaches for the treatment of hyperuricemia and related diseases.
Competing Interests: Declaration of competing interest As the corresponding author, I am providing this statement on behalf of all authors of the manuscript titled Unveiling Overlooked Pathways: The Uric Acid Catabolism Genes in the Human Genome, by Rodrigues et al. We declare the following potential sources of bias and conflicts of interest: All authors declare that we have no conflicts of interest to disclose. We have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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