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Lysine and its pathway metabolites have been identified as novel biomarkers for metabolic and vascular diseases. The role of them in the identification of moyamoya disease (MMD) has not been elucidated. This study aimed to determine the association between lysine pathway metabolites and the presence of MMD. We prospectively enrolled 360 MMD patients and 89 healthy controls from September 2020 to December 2021 in Beijing Tiantan Hospital. Serum levels of lysine, pipecolic acid and 2-aminoadipic acid were measured by liquid chromatography-mass spectrometry. We employed logistic regression and restricted cubic spline to explore the association between these metabolites and the presence of MMD. Stratified analyses were also conducted to test the robustness of results. We observed that lysine levels in MMD patients were significantly higher and pipecolic acid levels were significantly lower compared to HCs (both p < 0.001), while no difference was found in the level of 2-AAA between both groups. When comparing metabolites by quartiles, elevated lysine levels were linked to increased odds for MMD (the fourth quartile [Q4] vs the first quartile [Q1]: odds ratio, 3.48, 95%CI [1.39–8.75]), while reduced pipecolic acid levels correlated with higher odds (Q4 vs Q1: odds ratio, 0.08; 95 % CI [0.03–0.20]). The restricted cubic spline found a L-shaped relationship between pipecolic acid level and the presence of MMD, with a cutoff point at 2.52 μmol/L. Robust results were also observed across subgroups. Elevated lysine levels were correlated with increased odds of MMD presence, while lower pipecolic acid levels were associated with higher odds of the condition. These results suggest potential new biomarkers for the identification of MMD. URL: https://www.chictr.org.cn/. Unique identifier: ChiCTR2200061889. [ABSTRACT FROM AUTHOR]

The occurence and development of tumors is a complicated process, which not only depends on the mutation or deletion of genes, but also is affected by epigenetic regulation. Accumulating evidences have shown that epigenetic modifications play fundamental roles in transcriptional regulation, heterochromatin formation, X chromosome inactivation, DNA damage response and tumor development. SET domain containing lysine methyltransferase 7 (SETD7) was initially identified as an important lysine methyltransferase, which methylated histone and non-histone proteins. These modifications play fundamental roles. Once this modification disorders, it can directly lead to cell abnormalities and cause many diseases. Studies have shown that SETD7 is related to the occurence and development of various tumors, but the methylation sites of SETD7 and its regulatory mechanism have not been fully elucidated. Tis article summarizes the research progress of the role of SETD7 on histone and non-histone methylation modification in tumors and the molecular mechanism, in order to provide new therapeutic targets for tumor pathogenesis and diagnosis. [ABSTRACT FROM AUTHOR]

The interactions between plants and nanomaterials (NMs) can shed light on the environmental consequences of nanotechnology. We used the major crop plant rice ( Oryza sativa L.) to investigate the uptake of gold nanoparticles (GNPs) coated with either negatively or positively charged ligands, over a 5-day period, in the absence or presence of one of two amino acids, aspartic acid (Asp) or lysine (Lys), acting as components of rice root exudates. The presence of Asp or Lys influenced the uptake and distribution of GNPs in rice, which depended on the electrical interaction between the coated GNPs and each amino acid. When the electrical charge of the amino acid was the same as that of the surface ligand coated onto the GNPs, the GNPs could disperse well in nutrient solution, resulting in increased uptake of GNPs into rice tissue. The opposite was true where the charge on the surface ligand was different from that on the amino acid, resulting in agglomeration and reduced Au uptake into rice tissue. The behavior of GNPs in the hydroponic nutrient solution was monitored in terms of agglomeration, particle size distribution, and surface charge in the presence and absence of Asp or Lys, which depended strongly on the electrostatic interaction. Results from this study indicated that the species of root exudates must be taken into account in assessing the bioavailability of nanomaterials to plants. [ABSTRACT FROM AUTHOR]

We previously showed that L-lysine (Lys) and a metabolite of Lys, L-saccharopine, suppressed autophagic proteolysis in C2C12 myotubes. However, the effects of other metabolites of Lys on protein turnover were unknown. We here investigated the effect of the Lys metabolites, L-2-aminoadipic acid (2-AA) and L-pipecolic acid (Pip), on protein turnover in C2C12 myotubes. 2-AA suppressed myofibrillar protein degradation evaluated by the 3-methylhistidine and autophagy activity evaluated by light chain 3-II at lower concentration (100 μM) than did Lys. On the other hand, Pip stimulated the mammalian target of rapamycin signaling activity. Additionally, 100 μM Pip significantly increased the rates of protein synthesis whereas 100 μM Lys had no effect. These results indicate that in C2C12 myotubes, 2-AA could suppress autophagy and Pip could stimulate the rates of protein synthesis, and these metabolites may contribute to exert effect of Lys on protein turnover. L-lysine metabolites, L-2-aminoadipic acid and L-pipecolic acid, have regulatory effects on proteolysis and protein synthesis. [ABSTRACT FROM PUBLISHER]

Abstract: Yellow (y) encodes a protein which is closely similar to major royal jelly proteins produced by bees. However, the function of y remains largely unknown. Metabolomic profiling was carried out on third instar Oregon R (OR) and yellow (y) Drosophila melanogaster larvae. Phenylalanine, tyrosine and DOPA were all elevated in y as might be expected since the mutation blocks melanin biosynthesis. The most consistent effects were related to lysine metabolism, with the lysine metabolite saccharopine being much higher in y. In addition, lysine acetate was elevated, and the levels of methyl lysines were lower, in y than in OR. [Copyright &y& Elsevier]

Yellow (y) encodes a protein which is closely similar to major royal jelly proteins produced by bees. However, the function of y remains largely unknown. Metabolomic profiling was carried out on third instar Oregon R (OR) and yellow (y) Drosophila melanogaster larvae. Phenylalanine, tyrosine and DOPA were all elevated in y as might be expected since the mutation blocks melanin biosynthesis. The most consistent effects were related to lysine metabolism, with the lysine metabolite saccharopine being much higher in y. In addition, lysine acetate was elevated, and the levels of methyl lysines were lower, in y than in OR. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: The aims of this study were to label the versatile amino acid l-lysine with 99mTc using 2,3-dimercapto-succinic acid (DMSA) as a chelator, and to assess its tumor imaging feasibility under in vivo and in vitro conditions, and finally to determine the subcellular biodistribution of this radiopharmaceutical. Materials and Methods: DMSA-l-lysine was chemically synthesized and labeled with sodium pertechnetate. Nuclear magnetic resonance (NMR) and mass spectral analysis of DMSA-l-lysine were conducted. Radiochemical purity was determined by thin-layer chromatography (TLC) and paper chromatography. Cellular uptake, competition and subcellular localization studies were performed in rat breast cancer cells (13762). In vivo studies of planar imaging and biodistribution studies were performed on female Fischer 344 rats. Medical Internal Radiation Dose (MIRD) dosimetry estimates were calculated. Results: Radiochemical purity (determined by radio-TLC and high-performance liquid chromatography) of these compounds was >95%. 99mTc-DMSA-l-lysine showed good uptake in in vitro cell culture assays and uptake was reduced in competition studies. 99mTc-DMSA-l-lysine accumulates in the nucleus as much as in the cytoplasm and it was also shown that accumulation of the 99mTc-DMSA-l-lysine in the nucleus increases as a function of a time. There was an increase in tumor-to-blood and tumor-to-muscle count density ratios. Tumor/background ratios were 5.75 at 1 hour and 6.87 at 2 hours. In vivo tissue distribution studies revealed that radiation dosimetry of blood-forming organs were within radiation dose limits. Conclusion: DMSA-l-lysine kits can be labeled with 99mTc easily and efficiently, with high radiochemical purity and cost-effectiveness. In vitro cellular uptake and scintigraphic imaging studies demonstrated the pharmacokinetic distribution and feasibility of using 99mTc-DMSA-l-lysine for tumor imaging. [Copyright &y& Elsevier]

Summary: Objective: Determine the kinetics of collagen crosslinking in adult bovine articular cartilage explants using radiolabel pulse-chase studies. Methods: Explant cultures of adult bovine articular cartilage were radiolabeled with [14C]lysine in medium including fetal bovine serum and ascorbate, and then maintained for chase periods up to 28 days. In some samples, β-aminopropionitrile (BAPN) was included during chase to inhibit lysyl oxidase-mediated collagen crosslinking. Tissue was hydrolyzed and analyzed for [14C]metabolites in the forms of lysine, hydroxylysine, dehydrodihydroxylysinonorleucine (ΔDHLNL), and hydroxylysyl pyridinoline (HP). Results: Explant cultures of adult bovine articular cartilage metabolized lysine into hydroxylysine and the collagen crosslinks, ΔDHLNL and HP. During chase, [14C]hydroxylysine maintained steady-state levels, [14C]DHLNL rose to a plateau, and [14C]HP increased gradually. Addition of BAPN inhibited formation of [14C]DHLNL. Analysis of raw data and that normalized to [14C]hydroxylysine gave characteristic time constants for formation of ΔDHLNL and HP crosslinks of 1–2 and 7–30 days, respectively. The distribution of [14C]lysine metabolites in collagen crosslinks was described by peak values in [14C]DHLNL/[14C]hydroxylysine of 0.047–0.064 and in [14C]HP/[14C]hydroxylysine of 0.03. Conclusion: Collagen crosslinks form in cartilage explants in vitro according to the classical lysyl oxidase-mediated pathway. [Copyright &y& Elsevier]