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Epigenetic Alterations in Alzheimer’s Disease and Its Therapeutic and Dietary Interventions
Published in Atanu Bhattacharjee, Akula Ramakrishna, Magisetty Obulesu, Phytomedicine and Alzheimer’s Disease, 2020
P. M. Aswathy, C. M. Shafeeque, Moinak Banerjee
In the one-carbon metabolism pathway, serine hydroxymethyltransferase 1 (SHMT1) is an enzyme that is involved in the reversible conversion of serine and tetrahydrofolate (THF) to glycine and 5,10-methylenetetrahydrofolate (5,10-MTHF). Methylene tetrahydrofolate reductase (MTHFR) is another enzyme in the pathway that irreversibly reduces 5,10-MTHF to 5-MTHF. 5-MTHF is the most stable and abundant form of the folate metabolites, and is the methyl donor for the pathway. Subsequently, methionine synthase (MTR) transfers a methyl group from 5-MTHF to homocysteine, forming methionine and tetrahydrofolate (THF), with the help of methionine synthase reductase (MTRR). Methionine is then converted back to SAM in a reaction catalyzed by methionine adenosyltransferase (MAT). Most of the SAM generated is used in transmethylation reactions, whereby SAM is converted to SAH by transferring the methyl group to diverse biological acceptors, including proteins and DNA. Vitamins B2 (riboflavin), B6 (pyridoxine), and B12 (cobalamin) are the cofactors of MTHFR, SHMT1, and MTRR, respectively, that are required for the maintenance of MTR in its active state (Figure 12.2).
Adenosine kinase deficiency
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
Methionine is an essential amino acid that is not metabolized by transamination as are other amino acids. The methionine cycle includes adenosylation of methionine (see Figure 69.1) catalyzed by methionine adenosyltransferase (MAT I/III) to AdoMet, donation of the methyl group forming AdoHcy via various methyltransferases, and hydrolysis by SAHH to generate homocysteine and adenosine.
RNA N6-methyladenosine methylation and skin diseases
Published in Autoimmunity, 2023
Yaqin Yu, Shuang Lu, Hui Jin, Huan Zhu, Xingyu Wei, Tian Zhou, Ming Zhao
In addition to the aforementioned conventional m6A methyltransferase, some other subordinate methyltransferases were recently discovered to also play an exceptional role in m6A modification. Vir-like m6A Methyltransferase Associated (VIRMA, also known as KIAA1429), another subunit component of the m6A methyltransferase complex, was found to recruit the core component METTL3/METTL14/WTAP for regioselective methylation near the 3’UTR and the stop codon [21]. Methyltransferase-like 16 (METTL16) methylates U6 snRNA and methionine adenosyltransferase 2 A (MAT2A) by targeting UACAGAGAA sequences [22]. The C-terminal region of zinc finger CCCH domain-containing protein 13 (ZC3H13) interacts with WTAP-Virilizer-Hakai and mediates its nuclear localisation to facilitate the onset of m6A modifications [23]. Another zinc finger protein, zinc finger CCHC-type containing 4 (ZCCHC4), methylates the AAC motif of human 28SrRNA [24]. RNA binding motif protein 15 (RBM15) and its paralogue RBM15B recruits the methyltransferase complex to the long non-coding RNA X-inactive specific transcript (XIST), leading to the formation of its m6A modification [25]. There are subunits like Cbl proto-oncogene like 1 (CBLL1, also known as Hakai) that also interact tightly with the core components [26,27], the specific mechanisms of which remain to be further investigated.
Non-alcoholic fatty liver disease establishment and progression: genetics and epigenetics as relevant modulators of the pathology
Published in Scandinavian Journal of Gastroenterology, 2023
Camila Cristiane Pansa, Letícia Ramos Molica, Karen C. M. Moraes
In NAFLD, the genetic profiling of advanced liver disease patients revealed that genes correlated to the 1 C metabolism reduced expression levels such of glycine N-methyltransferase (GNMT), betaine-homocysteine S methyltransferase (BHMT), cystathionine synthetase (CBS) and methionine adenosyltransferase (MAT1A) [118,119]. Moreover, other studies described that adenosylhomocysteinase (AHCY), MAT1A and methylenetetrahydrofolate dehydrogenase (MTHFD2) genes were hypermethylated, reducing SAM and changing global DNA methylation patterns and physiological problems [120]. To support those observations, methylome studies and transcriptome analysis correlated global hepatic DNA methylation with the progression of NAFLDs to more complex pathological conditions [93]. However, further studies are required to better understand the fine-tuning of DNA methylation and NAFLDs. In this context, the mechanistic characterization of elements that direct control epigenetic processes in NAFLD may be beneficial to developing innovative strategies in the treatment for hepatic steatosis treatment or even be used as a molecular marker in disease diagnostics [93,121].
High levels of blood glutamic acid and ornithine in children with intellectual disability
Published in International Journal of Developmental Disabilities, 2022
Muhammad Wasim, Haq Nawaz Khan, Hina Ayesha, Abdul Tawab, Fazal e Habib, Muhammad Rafique Asi, Mazhar Iqbal, Fazli Rabbi Awan
Among aminoacidopathies, phenylketonuria (PKU) is the most prevalent worldwide disorder (Wasim et al.2018a, 2018b, Brown and Lichter-Konecki 2016), but up till now from Pakistan, just a single report was recently published in which 18 patients have been described with high concentration of phenylalanine in their blood plasma, unfortunately, due to late diagnosis, all the patients already had developed irreversible intellectual disability (Ahmed et al.2019). Conversely, in the current study, not a single phenylketonuria (PKU) patient was identified, but interestingly, three intellectually disabled patients had high level of methionine (suspected for different disorders like homocystinuria (Cystathionine Beta synthase deficiency), Methionine adenosyltransferase I/III deficiency, Glycine N-Methyltransferase Deficiency, S-Adenosylhomocysteine hydrolase deficiency) (Nashabat et al.2018, Baric et al.2017, Baric et al.2005).