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Biomolecules
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Homocysteine: Biochemistry, Molecular Biology, and Role in Disease 2021
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Homocysteine: Biochemistry, Molecular Biology, and Role in Disease 2021

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

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 23534

Special Issue Editors

Prof. Dr. Anton Hermann

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Guest Editor
Department of Biosciences, University Salzburg, 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) is increasingly recognized as an important molecule in a wide variety of cellular functions. Hcy levels can be altered in different ways, including genetic factors, diet, lifestyle, several medications, etc. Clinical studies indicate the association between high Hcy levels and different pathological conditions, such as endothelial dysfunctions, high risk of thrombosis, age-dependent diseases, neuroinflammation, migraine, or schizophrenia. Recent data also show inflammation during high levels of hyperhomocysteinemia (hHcy) with increased levels of several cytokines and changes in DNA methylation. However, the causal relationship between several disorders and hHcy remains unclear in many cases. The level of the gasotransmitter hydrogen sulfide (H2S) decreases under hHcy conditions, which may mediate homocysteine-induced neurotoxicity, and on the other hand suggests that an increase of H2S may play a neuroprotective role.

This second SI is planned to focus on the role of homocysteine in diverse facets of biochemical, molecular biological, physiological, and pathological conditions and ways to prevent Hcy toxicity, including the use of B vitamines, antioxidants, H2S, and other protective molecules.

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

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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

  • cell physiology
  • ion channels
  • Ca2+-activated K+ channels
  • cellular excitability
  • gasotransmitters

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Published Papers (7 papers)

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Editorial

Jump to: Research, Review

3 pages, 180 KiB  
Editorial
Homocysteine: Biochemistry, Molecular Biology, and Role in Disease 2021
by Guzel Sitdikova and Anton Hermann
Biomolecules 2023, 13(7), 1111; https://0-doi-org.brum.beds.ac.uk/10.3390/biom13071111 - 13 Jul 2023
Cited by 1 | Viewed by 989
Abstract
Homocysteine is increasingly recognized as an important molecule in a wide variety of cellular functions [...] Full article
(This article belongs to the Special Issue Homocysteine: Biochemistry, Molecular Biology, and Role in Disease 2021)

Research

Jump to: Editorial, Review

16 pages, 1738 KiB  
Article
Hyperhomocysteinemia Increases Cortical Excitability and Aggravates Mechanical Hyperalgesia and Anxiety in a Nitroglycerine-Induced Migraine Model in Rats
by Elena Gerasimova, Olga Yakovleva, Daniel Enikeev, Ksenia Bogatova, Anton Hermann, Rashid Giniatullin and Guzel Sitdikova
Biomolecules 2022, 12(5), 735; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12050735 - 23 May 2022
Cited by 11 | Viewed by 2658
Abstract
Homocysteine is a sulfur-containing endogenous amino acid leading to neurotoxic effects at high concentrations. Population studies suggest an association between plasma homocysteine levels and the risk of migraine headaches. The aim of this study was to analyze the sensitivity of rats with prenatal [...] Read more.
Homocysteine is a sulfur-containing endogenous amino acid leading to neurotoxic effects at high concentrations. Population studies suggest an association between plasma homocysteine levels and the risk of migraine headaches. The aim of this study was to analyze the sensitivity of rats with prenatal hyperhomocysteinemia (hHCY) in respect of the development of behavioral correlates of headache and spreading cortical depolarization (CSD) in a migraine model induced by the administration of the nitric oxide (NO) donor nitroglycerin. Animals with hHCY were characterized by migraine-related symptoms such as mechanical hyperalgesia, high-level anxiety, photophobia, as well as an enhanced level of neuronal activity in the somatosensory cortex along with a lower threshold of CSD generation. Likewise, acute or chronic intermittent administration of nitroglycerin also induced the development of mechanical allodynia, photophobia and anxiety in control groups. However, these symptoms were more pronounced in rats with hHCY. Unlike hHCY, nitroglycerin administration did not affect the threshold of CSD generation, but like hHCY, increased the background neuronal activity in layers 2/3 and 4 of the cerebral cortex. The latter was more pronounced in animals with hHCY. Thus, the migraine profile associated with hHCY can be further exaggerated in conditions with enhanced levels of migraine triggering the gaseous transmitter NO. Our data are consistent with the view that high levels of plasma homocysteine can act as a risk factor for the development of migraine. Full article
(This article belongs to the Special Issue Homocysteine: Biochemistry, Molecular Biology, and Role in Disease 2021)
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12 pages, 2354 KiB  
Article
Did Homocysteine Take Part in the Start of the Synthesis of Peptides on the Early Earth?
by Sparta Youssef-Saliba, Anne Milet and Yannick Vallée
Biomolecules 2022, 12(4), 555; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12040555 - 08 Apr 2022
Cited by 2 | Viewed by 2461
Abstract
Unlike its shorter analog, cysteine, and its methylated derivative, methionine, homocysteine is not today a proteinogenic amino acid. However, this thiol containing amino acid is capable of forming an activated species intramolecularly. Its thiolactone could have made it an interesting molecular building block [...] Read more.
Unlike its shorter analog, cysteine, and its methylated derivative, methionine, homocysteine is not today a proteinogenic amino acid. However, this thiol containing amino acid is capable of forming an activated species intramolecularly. Its thiolactone could have made it an interesting molecular building block at the origin of life on Earth. Here we study the cyclization of homocysteine in water and show theoretically and experimentally that in an acidic medium the proportion of thiolactone is significant. This thiolactone easily reacts with amino acids to form dipeptides. We envision that these reactions may help interpret why a methionine residue is introduced at the start of all protein synthesis. Full article
(This article belongs to the Special Issue Homocysteine: Biochemistry, Molecular Biology, and Role in Disease 2021)
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13 pages, 669 KiB  
Article
The Effect of Three-Month Vitamin D Supplementation on the Levels of Homocysteine Metabolism Markers and Inflammatory Cytokines in Sera of Psoriatic Patients
by Alma Prtina, Nela Rašeta Simović, Tatjana Milivojac, Milorad Vujnić, Milkica Grabež, Dragan Djuric, Miloš P. Stojiljković, Valentina Soldat Stanković, Miodrag J. Čolić and Ranko Škrbić
Biomolecules 2021, 11(12), 1865; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11121865 - 11 Dec 2021
Cited by 9 | Viewed by 2921
Abstract
Psoriasis is an autoimmune and inflammatory skin disease. Psoriatic patients express higher levels of plasma homocysteine (Hcy) concentration and pro-inflammatory mediators than healthy people; this is frequently associated with vitamin D deficiency. The aim of this clinical study was to investigate the effects [...] Read more.
Psoriasis is an autoimmune and inflammatory skin disease. Psoriatic patients express higher levels of plasma homocysteine (Hcy) concentration and pro-inflammatory mediators than healthy people; this is frequently associated with vitamin D deficiency. The aim of this clinical study was to investigate the effects of high doses of vitamin D supplementation on the parameters of Hcy metabolism and cytokines in sera of psoriatic patients. This prospective study was conducted on 40 psoriatic patients who had the vitamin D deficiency. All patients received vitamin D 5000 IU/day for three months. Clinical and biochemical measurements were taken at baseline and at follow up (3 months). The results showed that the severity of clinical features, measured by the psoriasis area severity index (PASI) score, were considerably improved in patients after vitamin D supplementation. After vitamin D supplementation, most of the patients (n = 25 or 62.5%) had mild clinical form (p < 0.001). After twelve weeks of intervention period, there were significant increases in vitamin D and B12 serum levels in comparison to the levels that had been measured at the beginning of the study (56.77 ± 14.66 nmol/L and 301.08 ± 95.02 pg/mL vs. 103.85 ± 32.20 nmol/L and 362.81 ± 118.56 pg/mL, respectively; p < 0.001). Moreover, serum levels of Hcy and folate were significantly lower at the end of the study in comparison with the initial levels (12.45 ± 1.92 µmol/L and 8.01 ± 3.88 mg/mL vs. 10.38 ± 1.66 µmol/L and 6.27 ± 2.60 mg/mL, respectively). High doses of vitamin D supplementation led to a significant decrease in pro-inflammatory cytokines (IFN-ɤ, TNF-α, IL-1β, IL-6, IL-8, and IL-17) and high-sensitivity C-reactive protein (hsCRP), whereas the production of anti-inflammatory cytokines (IL-10, IL-5) was up-regulated. In conclusion, supplementation with high doses of vitamin D could be one of the possible preventive and therapeutic measures to reduce systemic inflammation in psoriatic patients. Full article
(This article belongs to the Special Issue Homocysteine: Biochemistry, Molecular Biology, and Role in Disease 2021)
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Review

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16 pages, 472 KiB  
Review
Metabolic Changes Induced by Cerebral Ischemia, the Effect of Ischemic Preconditioning, and Hyperhomocysteinemia
by Eva Baranovicova, Petra Hnilicova, Dagmar Kalenska, Peter Kaplan, Maria Kovalska, Zuzana Tatarkova, Anna Tomascova and Jan Lehotsky
Biomolecules 2022, 12(4), 554; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12040554 - 08 Apr 2022
Cited by 3 | Viewed by 2412
Abstract
1H Nuclear Magnetic Resonance (NMR) metabolomics is one of the fundamental tools in the fast-developing metabolomics field. It identifies and quantifies the most abundant metabolites, alterations of which can describe energy metabolism, activated immune response, protein synthesis and catabolism, neurotransmission, and many [...] Read more.
1H Nuclear Magnetic Resonance (NMR) metabolomics is one of the fundamental tools in the fast-developing metabolomics field. It identifies and quantifies the most abundant metabolites, alterations of which can describe energy metabolism, activated immune response, protein synthesis and catabolism, neurotransmission, and many other factors. This paper summarizes our results of the 1H NMR metabolomics approach to characterize the distribution of relevant metabolites and their alterations induced by cerebral ischemic injury or its combination with hyperhomocysteinemia in the affected tissue and blood plasma in rodents. A decrease in the neurotransmitter pool in the brain tissue likely follows the disordered feasibility of post-ischemic neurotransmission. This decline is balanced by the increased tissue glutamine level with the detected impact on neuronal health. The ischemic injury was also manifested in the metabolomic alterations in blood plasma with the decreased levels of glycolytic intermediates, as well as a post-ischemically induced ketosis-like state with increased plasma ketone bodies. As the 3-hydroxybutyrate can act as a likely neuroprotectant, its post-ischemic increase can suggest its supporting role in balancing ischemic metabolic dysregulation. Furthermore, the 1H NMR approach revealed post-ischemically increased 3-hydroxybutyrate in the remote organs, such as the liver and heart, as well as decreased myocardial glutamate. Ischemic preconditioning, as a proposed protective strategy, was manifested in a lower extent of metabolomic changes and/or their faster recovery in a longitudinal study. The paper also summarizes the pre- and post-ischemic metabolomic changes in the rat hyperhomocysteinemic models. Animals are challenged with hyperglycemia and ketosis-like state. A decrease in several amino acids in plasma follows the onset and progression of hippocampal neuropathology when combined with ischemic injury. The 1H NMR metabolomics approach also offers a high potential for metabolites in discriminatory analysis in the search for potential biomarkers of ischemic injury. Based on our results and the literature data, this paper presents valuable findings applicable in clinical studies and suggests the precaution of a high protein diet, especially foods which are high in Met content and low in B vitamins, in the possible risk of human cerebrovascular neuropathology. Full article
(This article belongs to the Special Issue Homocysteine: Biochemistry, Molecular Biology, and Role in Disease 2021)
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27 pages, 1144 KiB  
Review
Homocysteine, Vitamins B6 and Folic Acid in Experimental Models of Myocardial Infarction and Heart Failure—How Strong Is That Link?
by Zorislava Bajic, Tanja Sobot, Ranko Skrbic, Milos P. Stojiljkovic, Nenad Ponorac, Amela Matavulj and Dragan M. Djuric
Biomolecules 2022, 12(4), 536; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12040536 - 01 Apr 2022
Cited by 19 | Viewed by 5478
Abstract
Cardiovascular diseases are the leading cause of death and the main cause of disability. In the last decade, homocysteine has been found to be a risk factor or a marker for cardiovascular diseases, including myocardial infarction (MI) and heart failure (HF). There are [...] Read more.
Cardiovascular diseases are the leading cause of death and the main cause of disability. In the last decade, homocysteine has been found to be a risk factor or a marker for cardiovascular diseases, including myocardial infarction (MI) and heart failure (HF). There are indications that vitamin B6 plays a significant role in the process of transsulfuration in homocysteine metabolism, specifically, in a part of the reaction in which homocysteine transfers a sulfhydryl group to serine to form α-ketobutyrate and cysteine. Therefore, an elevated homocysteine concentration (hyperhomocysteinemia) could be a consequence of vitamin B6 and/or folate deficiency. Hyperhomocysteinemia in turn could damage the endothelium and the blood vessel wall and induce worsening of atherosclerotic process, having a negative impact on the mechanisms underlying MI and HF, such as oxidative stress, inflammation, and altered function of gasotransmitters. Given the importance of the vitamin B6 in homocysteine metabolism, in this paper, we review its role in reducing oxidative stress and inflammation, influencing the functions of gasotransmitters, and improving vasodilatation and coronary flow in animal models of MI and HF. Full article
(This article belongs to the Special Issue Homocysteine: Biochemistry, Molecular Biology, and Role in Disease 2021)
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53 pages, 4703 KiB  
Review
Hyperhomocysteinemia: Metabolic Role and Animal Studies with a Focus on Cognitive Performance and Decline—A Review
by Hendrik Nieraad, Nina Pannwitz, Natasja de Bruin, Gerd Geisslinger and Uwe Till
Biomolecules 2021, 11(10), 1546; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11101546 - 19 Oct 2021
Cited by 8 | Viewed by 5693
Abstract
Disturbances in the one-carbon metabolism are often indicated by altered levels of the endogenous amino acid homocysteine (HCys), which is additionally discussed to causally contribute to diverse pathologies. In the first part of the present review, we profoundly and critically discuss the metabolic [...] Read more.
Disturbances in the one-carbon metabolism are often indicated by altered levels of the endogenous amino acid homocysteine (HCys), which is additionally discussed to causally contribute to diverse pathologies. In the first part of the present review, we profoundly and critically discuss the metabolic role and pathomechanisms of HCys, as well as its potential impact on different human disorders. The use of adequate animal models can aid in unravelling the complex pathological processes underlying the role of hyperhomocysteinemia (HHCys). Therefore, in the second part, we systematically searched PubMed/Medline for animal studies regarding HHCys and focused on the potential impact on cognitive performance and decline. The majority of reviewed studies reported a significant effect of HHCys on the investigated behavioral outcomes. Despite of persistent controversial discussions about equivocal findings, especially in clinical studies, the present evaluation of preclinical evidence indicates a causal link between HHCys and cognition-related- especially dementia-like disorders, and points out the further urge for large-scale, well-designed clinical studies in order to elucidate the normalization of HCys levels as a potential preventative or therapeutic approach in human pathologies. Full article
(This article belongs to the Special Issue Homocysteine: Biochemistry, Molecular Biology, and Role in Disease 2021)
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