Amino Acids最新文献

{"title":"Applications of biaryl cyclization in the synthesis of cyclic enkephalin analogs with a highly restricted flexibility","authors":"Maria Różanowska,&nbsp;Gabriela Szczupaj,&nbsp;Michał Nowakowski,&nbsp;Priyadharshni Rajagopal,&nbsp;Piotr F. J. Lipiński,&nbsp;Joanna Matalińska,&nbsp;Aleksandra Misicka,&nbsp;Marek Lisowski,&nbsp;Łukasz Jaremko,&nbsp;Mariusz Jaremko","doi":"10.1007/s00726-023-03371-5","DOIUrl":"10.1007/s00726-023-03371-5","url":null,"abstract":"<div><p>A series of 10 cyclic, biaryl analogs of enkephalin, with Tyr or Phe residues at positions 1 and 4, were synthesized according to the Miyaura borylation and Suzuki coupling methodology. Biaryl bridges formed by side chains of the two aromatic amino acid residues are of the <i>meta</i>–<i>meta</i>, <i>meta</i>–<i>para</i>, <i>para</i>–<i>meta</i>, and <i>para</i>–<i>para</i> configuration. Conformational properties of the peptides were studied by CD and NMR. CD studies allowed only to compare conformations of individual peptides while NMR investigations followed by XPLOR calculations provided detailed information on their conformation. Reliability of the XPLOR calculations was confirmed by quantum chemical ones performed for one of the analogs. No intramolecular hydrogen bonds were found in all the peptides. They are folded and adopt the type IV β-turn conformation. Due to a large steric strain, the aromatic carbon atoms forming the biaryl bond are distinctly pyramidalized. Seven of the peptides were tested in vitro for their affinity for the µ-opioid receptor.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10907494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139995293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SNAT2-mediated regulation of estrogen and progesterone in the proliferation of goat mammary epithelial cells","authors":"Tingting Jiang,&nbsp;Xiaoyue Ma,&nbsp;Hanling Liu,&nbsp;Qianqian Jia,&nbsp;Jianguo Chen,&nbsp;Yi Ding,&nbsp;Ming Sun,&nbsp;Hongmei Zhu","doi":"10.1007/s00726-024-03382-w","DOIUrl":"10.1007/s00726-024-03382-w","url":null,"abstract":"<div><p>The development of the goat mammary gland is mainly under the control of ovarian hormones particularly estrogen and progesterone (P₄). Amino acids play an essential role in mammary gland development and milk production, and sodium-coupled neutral amino acid transporter 2 (SNAT2) was reported to be expressed in the mammary gland of rats and bovine mammary epithelial cells, which may affect the synthesis of milk proteins or mammary cell proliferation by mediating prolactin, 17β-estradiol (E₂) or methionine function. However, whether SNAT2 mediates the regulatory effects of E₂ and P₄ on the development of the ruminant mammary gland is still unclear. In this study, we show that E₂ and P₄ could increase the proliferation of goat mammary epithelial cells (GMECs) and regulate SNAT2 mRNA and protein expression in a dose-dependent manner. Further investigation revealed that SNAT2 is abundantly expressed in the mammary gland during late pregnancy and early lactation, while knockdown and overexpression of SNAT2 in GMECs could inhibit or enhance E₂- and P₄-induced cell proliferation as well as mammalian target of rapamycin (mTOR) signaling. We also found that the accelerated proliferation induced by SNAT2 overexpression in GMECs was suppressed by the mTOR signaling pathway inhibitor rapamycin. This indicates that the regulation of GMECs proliferation mediated by SNAT2 in response to E₂ and P₄ is dependent on the mTOR signaling pathway. Finally, we found that the total content of the amino acids in GMECs changed after knocking-down and overexpressing SNAT2. In summary, the results demonstrate that the regulatory effects of E₂ and P₄ on GMECs proliferation may be mediated by the SNAT2-transported amino acid pathway. These results may offer a novel nutritional target for improving the development of the ruminant mammary gland and milk production.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10891196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139929644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hybrid 2D/3D-quantitative structure–activity relationship studies on the bioactivities and molecular mechanism of antibacterial peptides","authors":"Qingguo Yan,&nbsp;Fangfang Wang,&nbsp;Bo Zhou,&nbsp;Xiangna Lin","doi":"10.1007/s00726-024-03381-x","DOIUrl":"10.1007/s00726-024-03381-x","url":null,"abstract":"<div><p>Antimicrobial peptide (AMP) is the polypeptide, which protects the organism avoiding attack from pathogenic bacteria. Studies have shown that there were some antimicrobial peptides with molecular action mechanism involved in crossing the cell membrane without inducing severe membrane collapse, then interacting with cytoplasmic target-nucleic acid, and exerting antibacterial activity by interfacing the transmission of genetic information of pathogenic microorganisms. However, the relationship between the antibacterial activities and peptide structures was still unclear. Therefore, in the present work, a series of AMPs with a sequence of 20 amino acids was extracted from DBAASP database, then, quantitative structure–activity relationship (QSAR) methods were conducted on these peptides. In addition, novel antimicrobial peptides with  stronger antimicrobial activities were designed according to the information originated from the constructed models. Hence, the outcome of this study would lay a solid foundation for the in-silico design and exploration of novel antibacterial peptides with improved activity activities.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10869384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139734216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel lncRNA-hidden polypeptide regulates malignant phenotypes and pemetrexed sensitivity in A549 pulmonary adenocarcinoma cells","authors":"Xiaobing Han,&nbsp;Liangxin Chen,&nbsp;Peng Sun,&nbsp;Xiuqing Wang,&nbsp;Qian Zhao,&nbsp;Lingfeng Liao,&nbsp;Dejin Lou,&nbsp;Nan Zhou,&nbsp;Yujun Wang","doi":"10.1007/s00726-023-03361-7","DOIUrl":"10.1007/s00726-023-03361-7","url":null,"abstract":"<div><p>The advance of high-throughput sequencing enhances the discovery of short ORFs embedded in long non-coding RNAs (lncRNAs). Here, we uncovered the production and biological activity of lncRNA-hidden polypeptides in lung adenocarcinoma (LUAD). In the present study, bioinformatics was used to screen the lncRNA-hidden polypeptides in LUAD. Analysis of protein expression was done by western blot or immunofluorescence assay. The functions of the polypeptide were determined by detecting its effects on cell viability, proliferation, migration, invasion, and pemetrexed (PEM) sensitivity. The protein interactors of the polypeptide were analyzed by mass spectrometry after Co-immunoprecipitation (Co-IP) assay. The results showed that the lncRNA LINC00954 was confirmed to encode a novel polypeptide LINC00954-ORF. The polypeptide had tumor-suppressor features in A549 cells by repressing cell growth, motility and invasion. Moreover, the polypeptide enhanced PEM sensitivity and suppressed growth in A549/PEM cells. The protein interactors of this polypeptide had close correlations with RNA processing, amide metabolic process, translation, RNA binding, RNA transport, and DNA replication. As a conclusion, the LINC00954-ORF polypeptide embedded in lncRNA LINC00954 possesses tumor-suppressor features in A549 and PEM-resistant A549 cells and sensitizes PEM-resistant A549 cells to PEM, providing evidence that the LINC00954-ORF polypeptide is a potential anti-cancer agent in LUAD.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10864564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139728820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intersubunit communication in glycogen phosphorylase influences substrate recognition at the catalytic sites","authors":"Nahori Kamada,&nbsp;Ayato Ikeda,&nbsp;Yasushi Makino,&nbsp;Hiroshi Matsubara","doi":"10.1007/s00726-023-03362-6","DOIUrl":"10.1007/s00726-023-03362-6","url":null,"abstract":"<div><p>Glycogen phosphorylase (GP) is biologically active as a dimer of identical subunits, each activated by phosphorylation of the serine-14 residue. GP exists in three interconvertible forms, namely GP<i>a</i> (di-phosphorylated form), GP<i>ab</i> (mono-phosphorylated form), and GP<i>b</i> (non-phosphorylated form); however, information on GP<i>ab</i> remains scarce. Given the prevailing view that the two GP subunits collaboratively determine their catalytic characteristics, it is essential to conduct GP<i>ab</i> characterization to gain a comprehensive understanding of glycogenolysis regulation. Thus, in the present study, we prepared rabbit muscle GP<i>ab</i> from GP<i>b</i>, using phosphorylase kinase as the catalyst, and identified it using a nonradioactive phosphate-affinity gel electrophoresis method. Compared with the half-half GP<i>a</i>/GP<i>b</i> mixture, the as-prepared GP<i>ab</i> showed a unique AMP-binding affinity. To further investigate the intersubunit communication in GP, its catalytic site was probed using pyridylaminated-maltohexaose (a maltooligosaccharide-based substrate comprising the essential dextrin structure for GP; abbreviated as PA-0) and a series of specifically modified PA-0 derivatives (substrate analogs lacking part of the essential dextrin structure). By comparing the initial reaction rates toward the PA-0 derivative (<i>V</i>_derivative) and PA-0 (<i>V</i>_PA-0), we demonstrated that the <i>V</i>_derivative/<i>V</i>_PA-0 ratio for GP<i>ab</i> was significantly different from that for the half-half GP<i>a</i>/GP<i>b</i> mixture. This result indicates that the interaction between the two GP subunits significantly influences substrate recognition at the catalytic sites, thereby providing GP<i>ab</i> its unique substrate recognition profile.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10858836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139715741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lateralization of the 5-HT1A receptors in the basolateral amygdala in metabolic and anxiety responses to chronic restraint stress","authors":"Habib Valipour,&nbsp;Gholam Hossein Meftahi,&nbsp;Gila Pirzad Jahromi,&nbsp;Alireza Mohammadi","doi":"10.1007/s00726-023-03380-4","DOIUrl":"10.1007/s00726-023-03380-4","url":null,"abstract":"<div><p>Behavioral and functional studies describe hemispheric asymmetry in anxiety and metabolic behaviors in responses to stress. However, no study has reported serotonergic receptor (the 5-HT_1A receptor) lateralization in the basolateral amygdala (BLA) in vivo on anxiety and metabolic behaviors under stress. In the present study, the effect of unilateral and bilateral suppression of the 5-HT_1A receptor in the BLA on anxiety, and metabolic responses to chronic restraint stress was assessed. Male Wistar rats 7 days after cannulation into the BLA received chronic restraint stress for 14 consecutive days. 20 minutes before induction of stress, WAY-100–635 (selective 5-HT_1A antagonist) or sterile saline (vehicle) was administered either uni- or bi-laterally into the BLA. Behavioral (elevated plus maze; EPM, and open field test), and metabolic parameter studies were performed. Results showed that stress causes a significant increase in weight gain compared to control. In the non-stress condition, the left and bilaterally, and in the stress condition the right, left, and both sides, inhibition of 5-HT_1A in the BLA reduced weight gain. In the restraint stress condition, only inhibition of the 5-HT_1A receptor in the left BLA led to decreased food intake compared to the control group. In stress conditions, inhibition of the 5-HT_1A receptor on the right, left, and bilateral BLA increased water intake compared to the stress group. Inhibition of the 5-HT_1A receptor on the left side of the BLA by WAY-100–635 induced anxiety-like behaviors in stressed rats. Similarly, WAY-100–635 on the left BLA effectively caused anxiety-like behaviors in both EPM and open field tests in the control animals. In conclusion, it seems that 5-HT_1A receptors in the left BLA are more responsible for anxiety-like behaviors and metabolic changes in responses to stress.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10858818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139715742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimicrobial and antitumor properties of anuran peptide temporin-SHf induce apoptosis in A549 lung cancer cells","authors":"Anet Antony,&nbsp;Anupama Kizhakke Purayil,&nbsp;Shilpa Olakkaran,&nbsp;Shweta Dhannura,&nbsp;Shamasoddin Shekh,&nbsp;Konkallu Hanumae Gowd,&nbsp;Hunasanahally Puttaswamygowda Gurushankara","doi":"10.1007/s00726-023-03373-3","DOIUrl":"10.1007/s00726-023-03373-3","url":null,"abstract":"<div><p>Temporin-SHf is a linear, ultra-short, hydrophobic, α-helix, and phe-rich cationic antimicrobial peptide. The antitumor activities and mechanism of temporin-SHf-induced cancer cell death are unknown. The temporin-SHf was synthesized by solid-phase Fmoc chemistry and antimicrobial and antitumor activities were investigated. Temporin-SHf was microbiocidal, non-hemolytic, and cytotoxic to human cancer cells but not to non-tumorigenic cells. It affected the cancer cells' lysosomal integrity and caused cell membrane damage. The temporin-SHf inhibited A549 cancer cell proliferation and migration. It is anti-angiogenic and causes cancer cell death through apoptosis. The molecular mechanism of action of temporin-SHf confirmed that it kills cancer cells by triggering caspase-dependent apoptosis through an intrinsic mitochondrial pathway. Owing to its short length and broad spectrum of antitumor activity, temporin-SHf is a promising candidate for developing a new class of anticancer drugs.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10847208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139690971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and characterization of endogenous biomarkers for hepatic vectorial transport (OATP1B3-P-gp) function using metabolomics with serum pharmacology","authors":"Yong-wen Jin,&nbsp;Yan-rong Ma,&nbsp;Ming-kang Zhang,&nbsp;Wen-bin Xia,&nbsp;Pei Yuan,&nbsp;Bo-xia Li,&nbsp;Yu-hui Wei,&nbsp;Xin-an Wu","doi":"10.1007/s00726-023-03363-5","DOIUrl":"10.1007/s00726-023-03363-5","url":null,"abstract":"<div><p>The organic anion-transporting polypeptide 1B3 and P-glycoprotein (P-gp) provide efficient directional transport (OATP1B3-P-gp) from the blood to the bile that serves as a key determinant of hepatic disposition of the drug. Unfortunately, there is still a lack of effective means to evaluate the disposal ability mediated by transporters. The present study was designed to identify a suitable endogenous biomarker for the assessment of OATP1B3-P-gp function in the liver. We established stably transfected HEK293T-OATP1B3 and HEK293T-P-gp cell lines. Results showed that azelaic acid (AzA) was an endogenous substrate for OATP1B3 and P-gp using serum pharmacology combined with metabolomics. There is a good correlation between the serum concentration of AzA and probe drugs of rOATP1B3 and rP-gp when rats were treated with their inhibitors. Importantly, after 5-fluorouracil-induced rat liver injury, the relative mRNA level and expression of rOATP1B3 and rP-gp were markedly down-regulated in the liver, and the serum concentration of AzA was significantly increased. These observations suggest that AzA is an endogenous substrate of both OATP1B3 and P-gp, and may serve as a potential endogenous biomarker for the assessment of the function of OATP1B3-P-gp for the prediction of changes in the pharmacokinetics of drugs transported by OATP1B3-P-gp in liver disease states.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10847190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139690972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of encapsulated water wire within self-assembled hydrophilic nanochannels, in a modified γ4-amino acid crystals: Tracking thermally induced changes of intermolecular interactions within a crystalline hydrate","authors":"Krishnayan Basuroy,&nbsp;Jose de Jesus Velazquez-Garcia,&nbsp;Simone Techert","doi":"10.1007/s00726-023-03372-4","DOIUrl":"10.1007/s00726-023-03372-4","url":null,"abstract":"<div><p>Nanostructures formed by the self-assembly of modified/unmodified amino acids have the potential to be useful in several biological/nonbiological applications. In that regard, the greater conformational space provided by γ-amino acids, owing to their additional backbone torsional degrees of freedom and enhanced proteolytic stability, compared to their α-counterparts, should be explored. Though, modified single amino acid-based nanomaterials such as nanobelts or hydrogels are developed by utilizing the monosubstituted γ-amino acids derived from the backbone homologation of phenylalanine (Phe). Examples of a single γ-amino acid-based porous nanostructure capable of accommodating solvent molecules are not really known. The crystal structures of a modified γ⁴(<i>R</i>)Phe residue, Boc-γ⁴(<i>R</i>)Phe-OH, at different temperatures, showed that hydrogen-bonded water molecules are forming a wire inside hydrophilic nanochannels. The dynamics of intermolecular interactions between the water wire and the inner wall of the channel with relation to the temperature change was investigated by analyzing the natural bonding orbital (NBO) calculation results performed with the single crystal structures obtained at different temperature points. The NBO results showed that from 325 K onward, the strength of water–water interactions in the water wire are getting weaker, whereas, for the water–inner wall interactions, it getting stronger, suggesting a favorable change in the orientation of water molecules with temperatures, for the latter.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10844418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139690974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating metabolic dysregulation in serum of triple transgenic Alzheimer’s disease male mice: implications for pathogenesis and potential biomarkers","authors":"Hongbin Zhuang,&nbsp;Xueshan Cao,&nbsp;Xiaoxiao Tang,&nbsp;Yongdong Zou,&nbsp;Hongbo Yang,&nbsp;Zhiyuan Liang,&nbsp;Xi Yan,&nbsp;Xiaolu Chen,&nbsp;Xingui Feng,&nbsp;Liming Shen","doi":"10.1007/s00726-023-03375-1","DOIUrl":"10.1007/s00726-023-03375-1","url":null,"abstract":"<div><p>Alzheimer’s disease (AD) is a multifactorial neurodegenerative disease that lacks convenient and accessible peripheral blood diagnostic markers and effective drugs. Metabolic dysfunction is one of AD risk factors, which leaded to alterations of various metabolites in the body. Pathological changes of the brain can be reflected in blood metabolites that are expected to explain the disease mechanisms or be candidate biomarkers. The aim of this study was to investigate the changes of targeted metabolites within peripheral blood of AD mouse model, with the purpose of exploring the disease mechanism and potential biomarkers. Targeted metabolomics was used to quantify 256 metabolites in serum of triple transgenic AD (3 × Tg-AD) male mice. Compared with controls, 49 differential metabolites represented dysregulation in purine, pyrimidine, tryptophan, cysteine and methionine and glycerophospholipid metabolism. Among them, adenosine, serotonin, N-acetyl-5-hydroxytryptamine, and acetylcholine play a key role in regulating neural transmitter network. The alteration of S-adenosine-<span>l</span>-homocysteine, S-adenosine-<span>l</span>-methionine, and trimethylamine-N-oxide in AD mice serum can served as indicator of AD risk. The results revealed the changes of metabolites in serum, suggesting that metabolic dysregulation in periphery in AD mice may be related to the disturbances in neuroinhibition, the serotonergic system, sleep function, the cholinergic system, and the gut microbiota. This study provides novel insights into the dysregulation of several key metabolites and metabolic pathways in AD, presenting potential avenues for future research and the development of peripheral biomarkers.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10844422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139690973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}