Amino Acids最新文献

{"title":"Taurine prevents mitochondrial dysfunction and protects mitochondria from reactive oxygen species and deuterium toxicity","authors":"Stephanie Seneff,&nbsp;Anthony M. Kyriakopoulos","doi":"10.1007/s00726-024-03440-3","DOIUrl":"10.1007/s00726-024-03440-3","url":null,"abstract":"<div><p>Taurine, although not a coding amino acid, is the most common free amino acid in the body. Taurine has multiple and complex functions in protecting mitochondria against oxidative-nitrosative stress. In this comprehensive review paper, we introduce a novel potential role for taurine in protecting from deuterium (heavy hydrogen) toxicity. This can be of crucial impact to either normal or cancer cells that have highly different mitochondrial redox status. Deuterium is an isotope of hydrogen with a neutron as well as a proton, making it about twice as heavy as hydrogen. We first explain the important role that the gut microbiome and the gut sulfomucin barrier play in deuterium management. We describe the synergistic effects of taurine in the gut to protect against the deleterious accumulation of deuterium in the mitochondria, which disrupts ATP synthesis by ATPase pumps. Moreover, taurine’s derivatives, N-chlorotaurine (NCT) and N-bromotaurine (NBrT), produced through spontaneous reaction of taurine with hypochlorite and hypobromite, have fascinating regulatory roles to protect from oxidative stress and beyond. We describe how taurine could potentially alleviate deuterium stress, primarily through metabolic collaboration among various gut microflora to produce deuterium depleted nutrients and deuterium depleted water, and in this way protect against leaky gut barrier, inflammatory bowel disease, and colon cancer.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-024-03440-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142938829","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":"Isoaspartate formation and irreversible aggregation of collapsin response mediator protein 2: implications for the etiology of epilepsy and age-related cognitive decline","authors":"Jeff X. Zhu,&nbsp;Dana W. Aswad","doi":"10.1007/s00726-024-03435-0","DOIUrl":"10.1007/s00726-024-03435-0","url":null,"abstract":"<div><p>Collapsin response mediator protein 2 (CRMP2) functions in the genesis and activity of neuronal connections in mammalian brain. We previously reported that a protein coincident with CRMP2 on 2D-gels undergoes marked accumulation of abnormal L-isoaspartyl sites in brain extracts of mice missing the repair enzyme, protein L-isoaspartyl methyltransferase (PIMT). To confirm and explore the significance of isoaspartyl damage in CRMP2, we expressed and purified recombinant mouse CRMP2 (rCRMP2). A polyclonal antibody made against the recombinant protein precipitated CRMP2 from brain extracts of PIMT-KO mice, but not from WT mice, suggesting that (1) the rCRMP2 antigen underwent significant isoAsp formation in the process of antibody production and (2) the isoAsp form of CRMP2 is considerably more immunogenic than the native protein. In vitro aging of rCRMP2 at pH 7.4, 37 °C for 0–28 days led to robust accumulation of isoAsp sites that were repairable by PIMT, and also induced a progressive accumulation of apparent dimers and higher-mass oligomers as judged by SDS-PAGE. A similar pattern of CRMP2 aggregation was observed in mice, with levels increasing throughout the lifespan. We conclude that CRMP2 is indeed a major target of PIMT-mediated protein repair in the brain; that isoAsp forms of CRMP2 are highly immunogenic; and that CRMP2 dysfunction makes a significant contribution to neuropathology in the PIMT-KO mouse.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-024-03435-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880547","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":"Comprehensive analysis of peripheral blood free amino acids in MASLD: the impact of glycine-serine-threonine metabolism","authors":"Masaaki Mino,&nbsp;Eiji Kakazu,&nbsp;Akitoshi Sano,&nbsp;Mio Tsuruoka,&nbsp;Hiroko Matsubara,&nbsp;Keisuke Kakisaka,&nbsp;Takayuki Kogure,&nbsp;Katsunori Sekine,&nbsp;Yoshihiko Aoki,&nbsp;Masatoshi Imamura,&nbsp;Michitaka Matsuda,&nbsp;Taiji Yamazoe,&nbsp;Taizo Mori,&nbsp;Sachiyo Yoshio,&nbsp;Jun Inoue,&nbsp;Atsushi Masamune,&nbsp;Tatsuya Kanto","doi":"10.1007/s00726-024-03433-2","DOIUrl":"10.1007/s00726-024-03433-2","url":null,"abstract":"<div><p>Little is known about how blood free amino acids (FAAs) change in metabolic dysfunction-associated steatotic liver disease (MASLD). This study aims to identify the imbalance of FAAs in MASLD and explore its correction as a potential therapeutic target. We analyzed plasma FAAs data from 23,036 individuals with steatosis information from a biobank in Japan, and 310 patients with MASLD were enrolled. According to diagnostic criteria for steatotic liver disease (SLD) or cardiometabolic criteria (CC), we divided the subjects into five groups: MASLD, metabolic dysfunction and alcohol-associated liver disease (MetALD), CC-SLD-, CC + SLD-, and CC-SLD + . Twenty FAAs were compared among these groups and among MASLD patients with pathological information. Among the 20 FAAs, the levels of 16 FAAs increased in CC + SLD- according to the number of matches with CC items associated with insulin resistance (IR). Steatosis enhanced most of these changes but serine (Ser) and threonine (Thr) were unaffected. Glycine (Gly), Ser and Thr were significantly decreased in patients according to steatosis grade. We investigated the association between these FAAs imbalances and pathogenesis using MASLD mouse models. In mice fed a high-fat, fructose, and cholesterol (FFC) diet, metabolomics and RNA sequencing analyses indicated that abnormality in Gly, Ser, and Thr metabolism in the liver was associated with mitochondrial dysfunction and enhanced glycolysis via pyruvate. High-Gly, Ser, and Thr diet ameliorated pathogenesis of MASLD in leptin-deficient mice. Most FAAs increase due to cardiometabolic abnormalities, particularly IR. However, interventions targeting the metabolism of Gly, Ser, and Thr have the potential to improve MASLD.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-024-03433-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880522","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":"Effect of D-amino acid metabolic enzyme deficiency on cancer development—diffuse large B-cell lymphoma onset and gene expression analyses in DASPO-knockout mice","authors":"Yusuke Nakade,&nbsp;Yasunori Iwata,&nbsp;Kenichi Harada,&nbsp;Yasuharu Sato,&nbsp;Masashi Mita,&nbsp;Kenji Hamase,&nbsp;Ryuichi Konno,&nbsp;Mayo Hayashi,&nbsp;Taku Kobayashi,&nbsp;Yuta Yamamura,&nbsp;Tadashi Toyama,&nbsp;Atsushi Tajima,&nbsp;Takashi Wada","doi":"10.1007/s00726-024-03426-1","DOIUrl":"10.1007/s00726-024-03426-1","url":null,"abstract":"<div><p>The relationship between D-AA metabolic enzymes and cancer development remains unclear. We aimed to investigate this relationship using mice deficient in D-AA-related metabolic enzymes. We examined mice lacking these enzymes for approximately 900 days and the effects of altered D-AA metabolism on cancer development based on lifespan, pathological findings, and gene expression. The lifespan of female <i>DASPO</i> -knockout (<i>DASPO</i>^{<i>−/−</i>}) mice was shorter than that of the other group mice; furthermore, these mice showed tumor-like masses in the liver, spleen, and small intestine. A pathological diagnosis of diffuse large B-cell lymphoma (DLBCL) was made. RNA sequencing of the liver samples showed specific alterations in the expression of 71 genes in <i>DASPO</i>^{<i>−/−</i>} mice compared with that in wild-type B6 mice; <i>RGS 1</i>, <i>MTSS1</i>, and <i>SMARCD 1</i> were identified as DLBCL-related genes. Patients with DLBCL exhibiting low <i>DASPO</i> expression demonstrated a shorter survival period than those showing high expression. However, the role of <i>DASPO</i> in DLBCL development is unclear. Therefore, future research should focus on B cells. <i>DASPO</i> may serve as novel biomarkers and therapeutic targets in cancer.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-024-03426-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880523","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":"Dipeptides in CSF and plasma: diagnostic and therapeutic potential in neurological diseases","authors":"Katharina Küper,&nbsp;Gernot Poschet,&nbsp;Julia Rossmann,&nbsp;Sven F. Garbade,&nbsp;Alexander Spiegelhalter,&nbsp;Dan Wen,&nbsp;Georg F. Hoffmann,&nbsp;Claus P. Schmitt,&nbsp;Thomas Opladen,&nbsp;Verena Peters","doi":"10.1007/s00726-024-03434-1","DOIUrl":"10.1007/s00726-024-03434-1","url":null,"abstract":"<div><p>Dipeptides (DPs), composed of two amino acids (AAs), hold significant therapeutic potential but remain underexplored. Given the crucial role of AAs in central nervous system (CNS) function, this study investigated the presence of DPs in cerebrospinal fluid (CSF) and their correlation with corresponding AAs, potentially indicating their role as AA donors. Plasma and CSF samples were collected from 43 children with neurological or metabolic conditions of unknown origin, including 23 with epilepsy. A panel of 33 DPs was quantified using UPLC-MS/MS. Out of 33 DPs, 18 were detectable in CSF and 20 in plasma, displaying high inter-individual variance. Gly-Asp, Gly-Pro, and Ala-Glu were consistently found in all CSF samples, while only Gly-Asp was universally detectable in plasma. Anserine and carnosine were prominent in CSF and plasma, respectively, with no other histidine-containing DPs observed. Generally, DP concentrations were higher in plasma than in CSF; however, anserine and Gly-Pro had similar concentrations in both fluids. Significant correlations were observed between specific DPs and their corresponding AAs in CSF (Gly-Glu, Gly-Pro and Ser-Gln) and plasma (Glu-Glu and Glu-Ser). Notably, patients with epilepsy had elevated medium anserine concentrations in CSF. This study is the first to demonstrate the presence of numerous DPs in CSF and plasma. Further research is needed to determine if DP patterns can support the diagnosis of neurological diseases and whether DP administration can modulate amino acid availability in the brain, potentially offering new therapeutic options, such as for defects in the amino acid transporter.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-024-03434-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821133","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":"Free amino acids accelerate the time-dependent inactivation of rat liver nucleotide pyrophosphatase/phosphodiesterase Enpp3 elicited by EDTA","authors":"Ana Romero,&nbsp;Guadalupe Cumplido-Laso,&nbsp;Ascensión Fernández,&nbsp;Javier Moreno,&nbsp;José Canales,&nbsp;Rui Ferreira,&nbsp;Juan López-Gómez,&nbsp;João Meireles Ribeiro,&nbsp;María Jesús Costas,&nbsp;José Carlos Cameselle","doi":"10.1007/s00726-024-03431-4","DOIUrl":"10.1007/s00726-024-03431-4","url":null,"abstract":"<div><p>Nucleotide-pyrophosphatases/phosphodiesterases (NPP/PDE) are membrane or secreted Zn²⁺-metallohydrolases of nucleoside-5´-monophosphate derivatives. They hydrolyze, for instance, ATP and 4-nitrophenyl-dTMP, and belong to the ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP) family that contains seven members (ENPP1-ENPP7). Earlier we had shown that an NPP/PDE activity solubilized and partially purified from rat liver membranes is inactivated by EDTA in a time-dependent fashion, an effect enhanced by glycine and blocked by the 4-nitrophenyl-dTMP. Here, we extended this observation to other free amino acids. Activity assays started after different incubation lengths with EDTA provided first-order, apparent inactivation constants (k_i(ap)). With the exception of cysteine (a strong inhibitor) and histidine (itself evoking a time-dependent inactivation), free amino acids themselves did not affect activity but increased k_i(ap). The results are compatible with a conformational change of NPP/PDE evoked by interaction with free amino acids. The enzyme preparation was analyzed to identify what ENPP family members were present. First, the hydrolytic activity on 2´,3´-cGAMP was assayed because until very recently ENPP1 was the only mammalian enzyme known to display it. 2´,3´-cGAMP hydrolase activity was clearly detected, but mass spectrometry data obtained by LC-MS/MS gave evidence that only rat Enpp3, Enpp4 and Enpp5 were present with low abundance. This finding coincided in time with a recent publication claiming that mouse Enpp3 hydrolyzes 2´,3´-cGAMP, and that Enpp1 and Enpp3 account for all the 2´,3´-cGAMP hydrolase activity in mice. So, our results are confirmatory of Enpp3 activity towards 2´,3´-cGAMP. Finally, the effect of amino acids could be relevant to NPP/PDE actions dependent on protein-protein interactions, like the known insulin-related effects of ENPP1 and possibly ENPP3.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"57 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-024-03431-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783860","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":"The application and prospects of antimicrobial peptides in antiviral therapy","authors":"Fei Yang,&nbsp;Yunqi Ma","doi":"10.1007/s00726-024-03427-0","DOIUrl":"10.1007/s00726-024-03427-0","url":null,"abstract":"<div><p>Antimicrobial peptides (AMPs) have broad-spectrum antimicrobial activity, enabling them to rapidly detect and eliminate targets. In addition, many AMPs are natural peptides, making them promising candidates for therapeutic drugs. This review discusses the basic properties and mechanisms of action of AMPs, highlighting their ability to disrupt microbial membranes and modulate host immune responses. It also reviews the current state of research into using AMPs against various viral infections, focusing on their therapeutic potential against viruses that contribute to the global health crisis. Despite promising developments, therapies based on AMPs still face challenges such as stability, toxicity, and production costs. In this text, we will discuss these challenges and the latest technological advances aimed at overcoming them. The combination of nanotechnology and bioengineering approaches offers new ways to enhance the delivery, efficacy, and safety of AMPs. We emphasize the importance of further research to fully exploit the potential of AMPs in antiviral therapy, advocating a multifaceted approach that includes optimizing clinical use and exploring synergies with existing antiviral drugs.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-024-03427-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142762024","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":"Synthesis of enantiomerically enriched β-substituted analogs of (S)-α-alanine containing 1-phenyl-1H-1,2,3-triazole groups","authors":"Artavazd S. Poghosyan,&nbsp;Emma A. Khachatryan,&nbsp;Anna F. Mkrtchyan,&nbsp;Volodya Mirzoyan,&nbsp;Anahit M. Hovhannisyan,&nbsp;Karapet R. Ghazaryan,&nbsp;Ela V. Minasyan,&nbsp;Peter Langer,&nbsp;Ashot S. Saghyan","doi":"10.1007/s00726-024-03430-5","DOIUrl":"10.1007/s00726-024-03430-5","url":null,"abstract":"<div><p>A synthesis of new enantiomerically enriched derivatives of (S)-α-aminopropionic acid, containing in the β-position 1,2,3-triazole groups coupled with a o-, m- and p-substituted phenyl residue, was developed based on Cu(I) catalyzed [3 + 2] cycloaddition of azides with alkynes. As the starting materials was used the square-planar Ni(II)complex of the Schiff base of propargylglycine with the chiral auxiliary BPB (Benzylprolylbenzophenone) and 1,4-substituted phenyl azides. The assignment of the (S)-absolute configuration of the α-carbon atom of the amino acid residue of the main diastereomeric complexes of the cycloaddition products was carried out on the basis of positive Cotton effects in the region of 480–580 nm of the circular dichroism spectra. The target amino acids were isolated from acid hydrolysates of diastereomeric complexes using ion-exchange demineralization and crystallization from aqueous ethanol. Additional confirmation of the absolute configuration and determination of the enantiomeric purity of the target amino acids were carried out by chiral HPLC analysis. As a result, seven new non-proteinogenic (S)-α-amino acids, containing in the β-position a 1,2,3-triazole moiety, were synthesized.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-024-03430-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142761860","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":"Multiple strategies of HSP antimicrobial peptide optimization to enhance antimicrobial activity","authors":"Xiaozhong Cheng,&nbsp;Yonghuang Zhang,&nbsp;Yan Zhang,&nbsp;Yajun Chen,&nbsp;Jianli Chen,&nbsp;Wei Wang,&nbsp;Guilan Zhu","doi":"10.1007/s00726-024-03428-z","DOIUrl":"10.1007/s00726-024-03428-z","url":null,"abstract":"<div><p>Antimicrobial peptides (AMPs) have caught the attention of researchers over the last couple of years due to their unique membrane lytic mechanism for combating antibiotic resistance, which differs from the molecular targets of traditional antibiotics. Although natural AMPs exhibit potential antimicrobial activity against a wide range of microorganisms, some drawbacks, such as toxicity, low antibacterial activity, and high production costs limit their clinical application. To enhance the antimicrobial activity of a series of HSP peptides derived from the natural peptide HSP-1, this study optimized them using a variety of strategies, including net charge, hydrophobic moment, hydrophobicity, and helicity. Optimizing the antimicrobial action of HSP peptides depended mostly on net charge, hydrophobic moment, and hydrophobicity rather than helicity. HSP-M4 may be designed to combat microbial infections because the antimicrobial activity and cytotoxicity assays showed that they exhibited low cytotoxicity and prominent antimicrobial activity, respectively.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-024-03428-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142714147","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":"Altered amino acid levels in young hypopituitarism: impact of NAFLD and insulin resistance","authors":"Yuwen Zhang,&nbsp;Jiting Qiu,&nbsp;Shouyue Sun,&nbsp;Xuqian Fang","doi":"10.1007/s00726-024-03429-y","DOIUrl":"10.1007/s00726-024-03429-y","url":null,"abstract":"<div><p>Elevated concentrations of amino acids (AAs) are commonly observed in patients with nonalcoholic fatty liver disease (NAFLD). Individuals with hypopituitarism (HP) are at a heightened risk of developing NAFLD due to factors such as visceral obesity, increased insulin resistance (IR), and disturbances in lipid metabolism. However, the changes in AAs concentrations associated with HP remain poorly understood. Therefore, our study aimed to investigate whether individuals with HP, who were not receiving growth hormone replacement therapy (GHRT), exhibited altered AAs compared to controls (CTs), and whether these AAs were associated with IR, the presence of NAFLD, and the Metabolic Syndrome (MetS) score. The AAs profiles of 133 young males with HP (age: 24.5 ± 5.9; 57 with NAFLD and 76 without NAFLD) and 90 age and BMI-matched CTs were analyzed using untargeted metabolomics. The results revealed that most AAs were found to be elevated in subjects with HPs compared to CTs. Glutamate, glutamine, norleucine, and branched-chain amino acids (BCAAs) (leucine and valine) were correlated with the homeostasis model assessment of insulin resistance (HOMA-IR), with glutamate and norleucine showing independent linkage. Glutamate and proline levels were specifically associated with MetS score, while alanine and proline linked to NAFLD. Given that elevated glutamate and BCAAs levels have higher prevalence of NAFLD, we hypothesized that the changes in AAs observed in HPs may be attributed to the impact of NAFLD and IR.</p></div>","PeriodicalId":7810,"journal":{"name":"Amino Acids","volume":"56 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00726-024-03429-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142691868","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}