Does Risk of Hyperhomocysteinemia Depend on Thiol-Disulfide Exchange Reactions of Albumin and Homocysteine?

Coppo, Lucia; Scheggi, Simona; DeMontis, Graziella; Priora, Raffaella; Frosali, Simona; Margaritis, Antonios; Summa, Domenico; DiGiuseppe, Danila; Ulivelli, Monica; DiSimplicio, Paolo Cherubini

doi:10.1089/ars.2021.0269

Cited by 3 publications

(2 citation statements)

References 320 publications

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“…Some studies have suggested that homocysteine induces arteritis, which is associated with hypertension and atherosclerosis [22] . Similarly, other studies have found elevated homocysteine to be associated with cardiovascular and neurological disease [23] .…”

Section: Discussionmentioning

confidence: 73%

Gender - and age-related differences in plasma metabolic fingerprinting of healthy populations

Xie,

Tao,

et al. 2023

Preprint

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Background/Aims: The objective of this study was to investigate potential differences in the plasma metabolic fingerprinting of healthy individuals based on sex and age. Methods: Blood specimens were collected from patients at the First Affiliated Hospital of Nanchang University for health check-ups. The specimens were randomly divided into discovery and validation groups, maintaining a 1:1 ratio. Small molecule metabolites in each sample were detected using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). Results: Plasma metabolites exhibited significant variations between sexes and age groups in our population. A comparison between men and women revealed 13 differential metabolites, with acetylcholine having the highest differential expression (AUC = 0.909). A diagnostic model (model 1) combining PC 36:4, acetylcholine, L-threonine, and arginine showed an AUC value of 0.973, a sensitivity of 91%, and a specificity of 94%. Model 2, which combined creatinine, L-methionine, acetylcholine, and L-tyrosine, had an AUC value of 0.955, a sensitivity of 94%, and a specificity of 88%. When comparing age groups, the OPLSDA model exhibited moderate stability and higher predictive efficacy in the 18-44 and 45-67 age groups. The differential metabolites were predominantly lipid molecules, with the highest AUC found in Dehydroisoandrosterone-3-sulfate. Additionally, we observed that LysoPC 20:1, LysoPC 20:0, PI 38:5, PC 40:3, 3-Hydroxydodecanoic acid 12:0(3-OH), Choline, N-Formyl-L-methionine, and Homocystine positively correlated with age, while Dehydroisoandrosterone-3-sulfate and Piperine were negatively correlated with age. Conclusion: These differential metabolites provide insights for the prevention and treatment of age- and gender-related diseases.

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Section: Discussionmentioning

confidence: 73%

Gender - and age-related differences in plasma metabolic fingerprinting of healthy populations

Xie,

Tao,

et al. 2023

Preprint

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“…Additionally, elevated Hcy levels can forecast cognitive decline in healthy elderly individuals [ 9 , 72 , 73 , 74 ]. Therefore, Hcy also exhibits promise as a predictive indicator for AD, and counteracting Hcy-induced neurotoxicity might emerge as an innovative approach for preventing and treating AD [ 2 , 6 , 73 , 74 , 75 ].…”

Section: Discussionmentioning

confidence: 99%

Alzheimer’s Disease-like Pathological Features in the Dorsal Hippocampus of Wild-Type Rats Subjected to Methionine-Diet-Evoked Mild Hyperhomocysteinaemia

Kovalska,

Hnilicova,

Kalenska

et al. 2023

Cells

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Multifactorial interactions, including nutritional state, likely participate in neurodegeneration’s pathogenesis and evolution. Dysregulation in methionine (Met) metabolism could lead to the development of hyperhomocysteinaemia (hHcy), playing an important role in neuronal dysfunction, which could potentially lead to the development of Alzheimer’s disease (AD)-like pathological features. This study combines proton magnetic resonance spectroscopy (1H MRS) with immunohistochemical analysis to examine changes in the metabolic ratio and histomorphological alterations in the dorsal rat hippocampus (dentate gyrus—DG) subjected to a high Met diet. Male Wistar rats (420–480 g) underwent hHcy evoked by a Met-enriched diet (2 g/kg of weight/day) lasting four weeks. Changes in the metabolic ratio profile and significant histomorphological alterations have been found in the DG of hHcy rats. We have detected increased morphologically changed neurons and glial cells with increased neurogenic markers and apolipoprotein E positivity parallel with a diminished immunosignal for the N-Methyl-D-Aspartate receptor 1 in hHcy animals. A Met diet induced hHcy, likely via direct Hcy neurotoxicity, an interference with one carbon unit metabolism, and/or epigenetic regulation. These conditions lead to the progression of neurodegeneration and the promotion of AD-like pathological features in the less vulnerable hippocampal DG, which presents a plausible therapeutic target.

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Hyperhomocysteinemia: a modern view of the problem (literature review)

Lutsyuk,

Zaichko,

Nekrut

et al. 2024

Rep. of Vinnytsia Nation. Med. Univ.

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Annotation. The purpose of the work was to systematize modern scientific information on the etiology and mechanisms of development of hypohomocysteinemia, to argue its possible role in pathology and the expediency of correcting a low level of homocysteine. The analysis and generalization of the results of scientific research for the years 2012-2023, selected on the basis of information search in the scientometric databases Scopus, Web of Science, PubMed, MEDLINE, Google Scholar, was carried out. Hypohomocysteinaemia is a metabolic disorder that occurs in 0.5-1% of the population and is genetically determined or acquired. Recognised causes of hypohomocysteinaemia include a mutation of the NFE2L2 gene, and acquired causes include high doses of vitamins and trace elements with hypohomocysteinemic effects, primarily vitamins B6, B9, B12. Hypohomocysteinaemia can be caused by factors such as nutritional deficiency of methionine, N-acetylcysteine, insulin, pregnancy, and coronavirus disease, but this disorder is often idiopathic. The biochemical mechanisms of hypohomocysteinemia include excessive activation of methyltransferase reactions, increased need for homocysteine and cysteine in the face of increased glutathione intake, increased activity of transsulfuration processes involving cystathionine beta-synthase, separation of homocysteine from blood proteins and increased urinary excretion. The clinical significance of hypohomocysteinemia is due to a decrease in numerous physiological functions of homocysteine, which leads to a reduced ability to respond to oxidative stress and certain types of toxins, and increases the risk of developing idiopathic peripheral neuropathy, Parkinson's and Alzheimer’s diseases. There are no special approaches to the prevention and correction of hypohomocysteinaemia, which indicates the prospects for further research into this metabolic phenomenon and the development of new pharmacotherapeutic approaches.

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Does Risk of Hyperhomocysteinemia Depend on Thiol-Disulfide Exchange Reactions of Albumin and Homocysteine?

Cited by 3 publications

References 320 publications

Gender - and age-related differences in plasma metabolic fingerprinting of healthy populations

Gender - and age-related differences in plasma metabolic fingerprinting of healthy populations

Alzheimer’s Disease-like Pathological Features in the Dorsal Hippocampus of Wild-Type Rats Subjected to Methionine-Diet-Evoked Mild Hyperhomocysteinaemia

Hyperhomocysteinemia: a modern view of the problem (literature review)

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