Amino Acids最新文献

Agmatine, a natural polyamine generated from arginine by arginine decarboxylase (ADC), has attracted increasing attention because of its pleiotropic beneficial effects on neuroprotection, lifestyle-related diseases, and gut-brain axis-mediated pathways. Although mammals appear to possess only limited capacity to synthesize endogenous agmatine, accumulating evidence suggests that agmatine derived from diet and the gut microbiota contributes to systemic levels of this polyamine. Previous studies have revealed that Aspergillus oryzae, the filamentous fungus foundational to traditional Japanese cuisine and indispensable for starch saccharification in sake, miso, soy sauce, mirin, and other fermented foods, produces high levels of agmatine specifically under solid-state cultivation. Subsequent studies identified a novel pyruvoyl-dependent ADC (Ao-ADC1) responsible for this unique agmatine production. This mini-review summarizes current knowledge on solid-state cultivation-specific agmatine production by A. oryzae, with a particular focus on the discovery and biochemical characteristics of Ao-ADC1. These findings challenge the commonly accepted notion that ascomycetes lack ADC. Understanding the molecular rationale and physiological significance of this unique agmatine biosynthetic pathway provides a foundation for rational strategies to enhance agmatine production in A. oryzae and for the development of agmatine-enriched fermented foods and nutraceuticals. Furthermore, integrating this fungal pathway with emerging insights into microbe-host interactions may further illuminate how fermentation-derived agmatine contributes to human health through gut-brain axis mediated mechanisms.

Hemodialysis (HD) and hemodiafiltration (HDF) procedures have limited efficacy regarding removal of selected toxins. Tryptophan (Trp) metabolites formed through the kynurenine (KYN) pathway are known to contribute to kidney failure (KF) complications, some of which may affect the survival of neurons. The aim of this study was to investigate the removal of Trp and its metabolites, KYN, kynurenic acid (KYNA) and 3-hydroxykynurenine (3-OHKYN) in patients treated by HD or HDF and the impact of patients' comorbidities on toxins removal. The study was conducted in 50 patients with KF. Serum level of free fractions of Trp and its metabolites were measured before and after a dialysis session through high performance liquid chromatography. The serum concentration of Trp, as well as 3-OHKYN/KYN ratio remained unchanged, whereas the concentration of KYN, KYNA, 3-OHKYN, together with KYN/Trp ratio significantly decreased after dialysis procedures. The indices KYNA/KYN and KYNA/3-OHKYN increased. In patients with heart failure, higher reduction ratio (RR) of KYN was found, whereas in patients with diabetes higher KYN RR and lower KYNA RR was observed. In patients without residual kidney function, KYNA RR was significantly higher compared to patients with preserved diuresis. RR of all tested metabolites did not differ between HD and HDF treated patients. In KF, Trp metabolites were removed from the blood during dialysis procedures with different efficacies. Targeted strategies to lower KYN pathway metabolites concentration may be beneficial in patients with KF and selected comorbidities.

Glycation due to increased blood sugar levels aggravates diabetic complications. Glycation hampers the structural and functional integrity of human serum albumin (HSA). Acetylsalicylic acid (ASA)/aspirin exhibits anti-glycation properties. Although the precise molecular mechanism of ASA in glycation has not yet been conclusively demonstrated, acetylation has been considered the central mechanism underlying its biological action. The present study aims to unveil the specific mechanism of action of ASA on glycated HSA through meticulously designed approaches. Fluorescence and UV-visible spectroscopy were used to analyse glycation adducts in the presence of ASA. ANS-based fluorescence spectroscopy, sodium dodecyl sulfate polyacrylamide gel electrophoresis, Fourier transform infrared spectroscopy, field-emission scanning electron microscopy, and high-performance liquid chromatography were used to study the structural modifications of glycated HSA in the presence of ASA. Furthermore, we investigated functional modifications in glycated HSA using nuclear magnetic resonance spectroscopy. The analyzed data showed a direct association between glycation and the impaired structural and functional integrity of HSA, which was partially restored by ASA. Our data corroborate that ASA's prominent anti-glycation activity may be attributable to mechanisms other than acetylation.

Hypusine is a unique amino acid synthesized on the eukaryotic initiation factor 5 A (EIF5A) from the polyamine spermidine by deoxyhypusine synthase (DHPS). Hypusination of EIF5A plays a key role in translation. Here, we examined the contribution of the epithelial hypusination pathway to gastric inflammation induced by Helicobacter pylori. Immunohistochemical analyses revealed increased expression of DHPS and hypusinated EIF5A (EIF5A^Hyp) in the gastric mucosa of patients with H. pylori gastritis compared to uninfected individuals, notably within gastric epithelial cells (GECs) and immune infiltrates. Then, we created a mouse model with epithelial-specific deletion of Dhps (Dhps^Δepi) and confirmed the reduction of DHPS and EIF5A^Hyp in GECs. H. pylori-infected Dhps^Δepi mice exhibited an attenuation of gastric histologic inflammation scores compared with infected Dhps^fl/+ controls, without alteration in bacterial colonization levels. Quantitative proteomics of isolated GECs showed that Dhps deletion altered the expression of proteins involved in organismal injury, cancer, and gastrointestinal diseases in naïve mice. Upon H. pylori infection, inflammatory and immune response proteins, including signaling factors and immunoglobulin mediators, were less induced in Dhps^Δepi GECs, and pathways linked to tissue injury and inflammation were selectively downregulated. Together, these findings demonstrate that epithelial hypusination supports H. pylori-driven gastric inflammation without affecting bacterial persistence. Targeting DHPS-dependent EIF5A hypusination may thus represent a novel therapeutic strategy to limit H. pylori-associated mucosal injury and disease progression.

The methanogenic archaeon Methanothermobacter marburgensis offers a promising alternative to traditional bacterial systems for the sustainable production of proteinogenic amino acids (AAs), eliminating the need for sugar-based feedstock. In this study, we quantitatively examined AA excretion and consumption in fed-batch cultivation mode in bioreactors under varying ammonium (NH₄⁺) concentrations and gas compositions. M. marburgensis demonstrated excretion of a wide spectrum of AAs with distinct profiles shaped by nitrogen availability. While high NH₄⁺ concentrations suppressed total AA excretion, NH₄⁺ limited conditions triggered alanine accumulation followed by its re-assimilation, suggesting a regulatory mechanism linked to nitrogen stress. Moreover, carbon limitation and nitrogen excess resulted in the production of an AA pattern including asparagine. Despite lower overall productivity compared to engineered bacterial strains, M. marburgensis exhibited the unique ability to simultaneously excrete multiple AAs without requiring organic carbon input. These findings advance the feasibility of using methanogens for AA bioprocessing and the development of archaea as next-generation microbial cell factories.

Amyotrophic lateral sclerosis (ALS) and Charcot-Marie-Tooth disease (CMT) are two distinct neurodegenerative disorders. While ALS is characterised by rapidly progressive motor neuron degeneration, leading to severe complications and death, CMT as a peripheral neuropathy is less severe, and patients have a longer life span, although with a compromised quality of life. Despite their clinical differences, current knowledge suggests that familial ALS (fALS) and CMT may share common genetic and molecular mechanisms. We aimed to identify shared genes mutations and molecular pathways between fALS and CMT through a literature and database search. Thirteen genes were identified, involved in distinct cellular processes: axonal transport (DYNC1H1, KIF5A, SPG11, DCTN1), protein homeostasis (NEFH, VCP, SOD1), RNA metabolism (GARS, SETX), cellular stress response (HSPB1, FIG4), and mitochondrial function (MFN2, CHCHD10). While these linkages to the two diseases are rare for each gene, understanding possible mechanistic commonalities at the molecular level can initiate new research directions, help in identifying additional common genes between neurodegenerative disorders, and improve diagnostics.

Polyamines - putrescine, spermidine, and spermine - are ubiquitous cationic molecules that are essential for cellular proliferation and homeostasis. Their intracellular concentrations decline with age, contributing to physiological and cognitive deterioration. Recent studies have revealed that spermidine supplementation extends lifespan and improves cognitive and cardiac function in various model organisms, suggesting that maintaining polyamine balance has anti-aging potential. Polyamine metabolism is tightly regulated through biosynthesis, degradation, and transport; however, age-associated upregulation of spermine oxidase (SMOX) and accumulation of its toxic byproduct acrolein promote oxidative damage and cellular senescence. Suppressing SMOX activity or polyamine degradation attenuates senescence markers and DNA damage, highlighting spermine catabolism as a therapeutic target. Polyamines also modulate epigenetic regulation, including DNA methylation and histone acetylation, thereby influencing gene expression and chromatin structure during aging. Moreover, polyamine-dependent hypusination of eIF5A sustains protein synthesis in senescent cells. These multifaceted actions indicate that polyamine metabolism integrates redox control, translational regulation, epigenetic maintenance and autophagy to determine cellular and organismal longevity. While animal studies demonstrate clear anti-aging effects of spermidine and spermine, human clinical evidence remains limited, with variable outcomes likely due to bioavailability and metabolic conversion. Future strategies combining dietary or probiotic polyamine enhancement, enzyme-targeted inhibitors, and personalized metabolic interventions hold promise for extending healthspan. Collectively, maintaining optimal polyamine homeostasis emerges as a key approach to counteract aging and age-related diseases.

Mucuna pruriens (MP), or velvet bean, has been used as an alternative medicine in India for over 4500 years, predominantly due to the natural abundance of the non-protein amino acid L-3,4-dihydroxyphenylalanine (L-DOPA). L-DOPA (levodopa) is used to treat Parkinson's disease (PD), a condition in which the progressive loss of dopaminergic neurons causes dopamine deficiency and impaired motor function. Although L-DOPA increases dopamine synthesis in the remaining dopaminergic neurones in the PD brain, the rate of disease progression appears to remain unchanged. Some studies have demonstrated improved outcomes in patients taking MP preparations compared to those undergoing traditional L-DOPA therapy. There is evidence that the canonical amino acids and L-DOPA precursors L-phenylalanine (L-Phe) and L-tyrosine (L-Tyr) can increase dopamine synthesis and also protect against the mistaken incorporation of L-DOPA into proteins during protein synthesis. The current study developed and validated a sensitive HILIC-TQMS method for the quantification of L-DOPA and related amino acids in MP preparations. Analysis revealed that L-DOPA levels were 66.2% to 82.7% of the values reported by manufacturers. Tyr and Phe were present in both free and protein bound forms in all 5 preparations analysed, potentially offering protection against the mistaken incorporation of L-DOPA into proteins and promoting increased dopamine synthesis. These findings suggest that the additional reported benefits of MP supplements for PD treatment might, in part, be attributable to the presence of these amino acids, further supporting the need to investigate the administration of L-DOPA and its cognate amino acid in symptomatic treatment of PD.