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Biomolecules
Special Issues
Homocysteine and H2S in Health and Disease
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Homocysteine and H2S in Health and Disease

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Chemical Biology".

Deadline for manuscript submissions: closed (31 December 2024) | Viewed by 14536

Special Issue Editors

Prof. Dr. Anton Hermann

E-Mail Website
Guest Editor
Department of Biosciences, University Salzburg, Hellbrunnerstr 34, A-5020 Salzburg, Austria
Interests: cell physiology; ion channels; Ca2+-activated K+ channels; cellular excitability; gasotransmitters
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Guzel F. Sitdikova

E-Mail Website
Guest Editor
Department of Physiology of Man and Animals, Kazan Federal University, 420008 Kazan, Russia
Interests: neurophysiology; development; homocysteine; ion channels; hydrogen sulfide; synaptic transmission; migraine; pain
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Homocysteine (Hcy) and hydrogen sulphide (H2S) are two active molecules produced both in the metabolic cycle of methionine that must be precisely regulated. An increased level of homocysteine in the plasms, called hyperhomocysteinemia (HHcy), may be the result of several hereditary and acquired factors, including deficiency or genetic polymorphism of enzymes associated with homocysteine metabolism, renal failure, deficit of vitamins B6, B9 and B12 and medication administration such as antiepileptic drugs or L-DOPA. HHcy induces oxidative stress and inflammation in many tissues and is associated with numerous pathologies like cardiovascular diseases, neurodegeneration, osteoporosis, migraine, epilepsy, developmental disorders, etc.

Hcy levels are regulated by remethylation and transsulfuration pathways. The key enzymes of transsulfuration pathways are cystathionine β-synthase and cystathionine γ-lyase, which are involved in the biosynthesis of H2S. In addition, H2S can be synthesized by the activity of cysteine aminotransferase and 3-mercaptopyruvate sulfurtransferase.

In this Special Issue, we will focus on the linkage between the metabolism of homocysteine and H2S, imbalance of homocysteine and H2S in different pathologies, mechanisms of protective effects of H2S in homocysteine toxicity, and approaches to maintain the endogenous balance between these two molecules to prevent this condition in patients.

Prof. Dr. Anton Hermann
Prof. Dr. Guzel F. Sitdikova
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • homocysteine (Hcy)
  • hydrogen sulfide (H2S)
  • oxidative stress
  • inflammation

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Related Special Issue

Published Papers (6 papers)

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Research

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18 pages, 10158 KiB  
Article
Prenatal Hyperhomocysteinemia Leads to Synaptic Dysfunction and Structural Alterations in the CA1 Hippocampus of Rats
by Tatyana Y. Postnikova, Alexandra V. Griflyuk, Natalia L. Tumanova, Nadezhda M. Dubrovskaya, Anastasia V. Mikhel, Dmitriy S. Vasilev and Aleksey V. Zaitsev
Biomolecules 2025, 15(2), 305; https://doi.org/10.3390/biom15020305 - 19 Feb 2025
Cited by 1 | Viewed by 543
Abstract
Prenatal hyperhomocysteinemia (HCY) is associated with neurodevelopmental deficits, yet its long-term impact on hippocampal synaptic function remains poorly understood. This study examines the effects of moderate maternal HCY on excitatory synaptic transmission in the CA1 region of the dorsal hippocampus in rat offspring [...] Read more.
Prenatal hyperhomocysteinemia (HCY) is associated with neurodevelopmental deficits, yet its long-term impact on hippocampal synaptic function remains poorly understood. This study examines the effects of moderate maternal HCY on excitatory synaptic transmission in the CA1 region of the dorsal hippocampus in rat offspring at juvenile (P21) and adult (P90) stages. Using field postsynaptic potential (fPSP) recordings, electron microscopy, and Western blot analysis, we observed a significant age-dependent decline in the efficiency of excitatory synaptic transmission in HCY-exposed rats. Electron microscopy revealed structural alterations, including synaptic vesicle agglutination in the stratum radiatum, suggesting impaired neurotransmitter release. Additionally, a significant reduction in pyramidal neuron density was observed in the CA1 region, although seizure susceptibility remained unchanged. Western blot analysis showed altered expression of Synapsin I, indicating presynaptic dysfunction. These findings suggest that moderate prenatal HCY leads to persistent deficits in synaptic transmission and structural integrity, potentially contributing to cognitive impairments in adulthood. Our results highlight the importance of maternal homocysteine levels in shaping hippocampal function and could offer insights into neurodevelopmental disorders associated with metabolic disturbances. Full article
(This article belongs to the Special Issue Homocysteine and H2S in Health and Disease)
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17 pages, 4071 KiB  
Article
Chronic Hyperhomocysteinemia Impairs CSD Propagation and Induces Cortical Damage in a Rat Model of Migraine with Aura
by Elena Gerasimova, Daniel Enikeev, Aleksey Yakovlev, Andrey Zakharov and Guzel Sitdikova
Biomolecules 2024, 14(11), 1379; https://doi.org/10.3390/biom14111379 - 29 Oct 2024
Cited by 1 | Viewed by 1609
Abstract
Hyperhomocysteinemia (hHCY) is a metabolic disorder characterized by elevated levels of homocysteine in plasma. hHCY correlates with a high risk of migraine headaches, especially migraine with aura. Cortical spreading depression (CSD) is a wave of depolarization passing through neurons and glial cells of [...] Read more.
Hyperhomocysteinemia (hHCY) is a metabolic disorder characterized by elevated levels of homocysteine in plasma. hHCY correlates with a high risk of migraine headaches, especially migraine with aura. Cortical spreading depression (CSD) is a wave of depolarization passing through neurons and glial cells of the cortex and is considered an electrophysiological correlate of migraine aura. The aim of the present study was to analyze neuronal activity and CSD in the somatosensory cortex of rats in vivo with prenatal hHCY and to assess cortex viability after 2 h of CSD generation. Female rats were fed a diet high in methionine, and their offspring with high homocysteine levels in plasma were further used in experiments. Recurrent CSD was evoked by local KCl application on the dura surface. Neuronal viability was assessed by measuring the activity of lactate dehydrogenase (LDH) in the brain and 2,3,5-triphenyltetrazolium chloride staining of the somatosensory cortex after two hours of CSD generation. Animals with hHCY exhibited higher neuronal activity, and more CSDs were generated in response to KCl, indicating higher cortical excitability. Propagation of recurrent CSD was impaired in supragranular cortical layers, and the recovery of multiple unit activity and evoked sensory potentials after CSD was delayed in the hHCY group. Finally, in animals with prenatal hHCY, an ischemic focus was identified as a consequence of multiple CSDs, along with elevated levels of LDH activity in brain tissues, suggestive of diminished neuronal viability. These findings imply that prolonged elevated levels of homocysteine may not only predispose to migraine with aura but also potentially elevate the risk of migrainous infarction. Full article
(This article belongs to the Special Issue Homocysteine and H2S in Health and Disease)
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Review

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26 pages, 2890 KiB  
Review
The Pivotal Role of One-Carbon Metabolism in Neoplastic Progression During the Aging Process
by Avisek Majumder, Shabana Bano and Kasturi Bala Nayak
Biomolecules 2024, 14(11), 1387; https://doi.org/10.3390/biom14111387 - 31 Oct 2024
Viewed by 2150
Abstract
One-carbon (1C) metabolism is a complex network of metabolic reactions closely related to producing 1C units (as methyl groups) and utilizing them for different anabolic processes, including nucleotide synthesis, methylation, protein synthesis, and reductive metabolism. These pathways support the high proliferative rate of [...] Read more.
One-carbon (1C) metabolism is a complex network of metabolic reactions closely related to producing 1C units (as methyl groups) and utilizing them for different anabolic processes, including nucleotide synthesis, methylation, protein synthesis, and reductive metabolism. These pathways support the high proliferative rate of cancer cells. While drugs that target 1C metabolism (like methotrexate) have been used for cancer treatment, they often have significant side effects. Therefore, developing new drugs with minimal side effects is necessary for effective cancer treatment. Methionine, glycine, and serine are the main three precursors of 1C metabolism. One-carbon metabolism is vital not only for proliferative cells but also for non-proliferative cells in regulating energy homeostasis and the aging process. Understanding the potential role of 1C metabolism in aging is crucial for advancing our knowledge of neoplastic progression. This review provides a comprehensive understanding of the molecular complexities of 1C metabolism in the context of cancer and aging, paving the way for researchers to explore new avenues for developing advanced therapeutic interventions for cancer. Full article
(This article belongs to the Special Issue Homocysteine and H2S in Health and Disease)
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17 pages, 712 KiB  
Review
The Imbalance of Homocysteine, Vitamin B12 and Folic Acid in Parkinson Plus Syndromes: A Review beyond Parkinson Disease
by Vasiliki Poulidou, Ioannis Liampas, Marianthi Arnaoutoglou, Efthimios Dardiotis and Vasileios Siokas
Biomolecules 2024, 14(10), 1213; https://doi.org/10.3390/biom14101213 - 26 Sep 2024
Cited by 1 | Viewed by 2134
Abstract
While there is a link between homocysteine (Hcy), B12 and folic acid and neurodegeneration, especially in disorders like Parkinson’s and Alzheimer’s diseases, its role in Parkinson plus syndromes (PPS) has only been partially investigated. It appears that elevated Hcy, along with an imbalance [...] Read more.
While there is a link between homocysteine (Hcy), B12 and folic acid and neurodegeneration, especially in disorders like Parkinson’s and Alzheimer’s diseases, its role in Parkinson plus syndromes (PPS) has only been partially investigated. It appears that elevated Hcy, along with an imbalance of its essential vitamin cofactors, are both implicated in the development and progression of parkinsonian syndromes, which represent different disease pathologies, namely alpha-synucleinopathies and tauopathies. Attributing a potential pathogenetic role in hyperhomocysteinemia would be crucial in terms of improving the diagnostic and prognostic accuracy of these syndromes and also for providing a new target for possible therapeutic intervention. The scope of this review is to focus on vitamin imbalance in PPS, with a special emphasis on the role of Hcy, B12 and folic acid in the neurodegenerative process and their implication in the therapeutic approach of these disorders. Full article
(This article belongs to the Special Issue Homocysteine and H2S in Health and Disease)
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35 pages, 5486 KiB  
Review
Complex Pathophysiology of Acute Kidney Injury (AKI) in Aging: Epigenetic Regulation, Matrix Remodeling, and the Healing Effects of H2S
by Shreyasi Gupta, Subhadeep Mandal, Kalyan Banerjee, Hebah Almarshood, Sathnur B. Pushpakumar and Utpal Sen
Biomolecules 2024, 14(9), 1165; https://doi.org/10.3390/biom14091165 - 17 Sep 2024
Cited by 2 | Viewed by 4473
Abstract
The kidney is an essential excretory organ that works as a filter of toxins and metabolic by-products of the human body and maintains osmotic pressure throughout life. The kidney undergoes several physiological, morphological, and structural changes with age. As life expectancy in humans [...] Read more.
The kidney is an essential excretory organ that works as a filter of toxins and metabolic by-products of the human body and maintains osmotic pressure throughout life. The kidney undergoes several physiological, morphological, and structural changes with age. As life expectancy in humans increases, cell senescence in renal aging is a growing challenge. Identifying age-related kidney disorders and their cause is one of the contemporary public health challenges. While the structural abnormalities to the extracellular matrix (ECM) occur, in part, due to changes in MMPs, EMMPRIN, and Meprin-A, a variety of epigenetic modifiers, such as DNA methylation, histone alterations, changes in small non-coding RNA, and microRNA (miRNA) expressions are proven to play pivotal roles in renal pathology. An aged kidney is vulnerable to acute injury due to ischemia-reperfusion, toxic medications, altered matrix proteins, systemic hemodynamics, etc., non-coding RNA and miRNAs play an important role in renal homeostasis, and alterations of their expressions can be considered as a good marker for AKI. Other epigenetic changes, such as histone modifications and DNA methylation, are also evident in AKI pathophysiology. The endogenous production of gaseous molecule hydrogen sulfide (H2S) was documented in the early 1980s, but its ameliorative effects, especially on kidney injury, still need further research to understand its molecular mode of action in detail. H2S donors heal fibrotic kidney tissues, attenuate oxidative stress, apoptosis, inflammation, and GFR, and also modulate the renin–angiotensin–aldosterone system (RAAS). In this review, we discuss the complex pathophysiological interplay in AKI and its available treatments along with future perspectives. The basic role of H2S in the kidney has been summarized, and recent references and knowledge gaps are also addressed. Finally, the healing effects of H2S in AKI are described with special emphasis on epigenetic regulation and matrix remodeling. Full article
(This article belongs to the Special Issue Homocysteine and H2S in Health and Disease)
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23 pages, 3072 KiB  
Review
How the Western Diet Thwarts the Epigenetic Efforts of Gut Microbes in Ulcerative Colitis and Its Association with Colorectal Cancer
by Avisek Majumder and Shabana Bano
Biomolecules 2024, 14(6), 633; https://doi.org/10.3390/biom14060633 - 29 May 2024
Cited by 5 | Viewed by 2830
Abstract
Ulcerative colitis (UC) is an autoimmune disease in which the immune system attacks the colon, leading to ulcer development, loss of colon function, and bloody diarrhea. The human gut ecosystem consists of almost 2000 different species of bacteria, forming a bioreactor fueled by [...] Read more.
Ulcerative colitis (UC) is an autoimmune disease in which the immune system attacks the colon, leading to ulcer development, loss of colon function, and bloody diarrhea. The human gut ecosystem consists of almost 2000 different species of bacteria, forming a bioreactor fueled by dietary micronutrients to produce bioreactive compounds, which are absorbed by our body and signal to distant organs. Studies have shown that the Western diet, with fewer short-chain fatty acids (SCFAs), can alter the gut microbiome composition and cause the host’s epigenetic reprogramming. Additionally, overproduction of H2S from the gut microbiome due to changes in diet patterns can further activate pro-inflammatory signaling pathways in UC. This review discusses how the Western diet affects the microbiome’s function and alters the host’s physiological homeostasis and susceptibility to UC. This article also covers the epidemiology, prognosis, pathophysiology, and current treatment strategies for UC, and how they are linked to colorectal cancer. Full article
(This article belongs to the Special Issue Homocysteine and H2S in Health and Disease)
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