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Vitamins and Derived Cofactors: Transport, Metabolism, Assembly and Deficiencies
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Vitamins and Derived Cofactors: Transport, Metabolism, Assembly and Deficiencies

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 25 July 2024 | Viewed by 6347

Special Issue Editors

Prof. Dr. Maria Barile

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Guest Editor
Department of Bioscience, Biotechnology and Biopharmaceutics, University of Bari A. Moro, Via Orabona, 4, I-70126 Bari, Italy
Interests: Rf and derived cofactors; transport metabolism; cofactor assembly; related human disorders
Special Issues, Collections and Topics in MDPI journals
Prof. Michele Galluccio

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Guest Editor
Department DiBEST (Biologia, Ecologia, Scienze della Terra), Unity of Molecular Biology, University of Calabria, Via P. Bucci 6C, 87036 Arcavacata di Rende, Italy
Interests: protein expression and purification; structure function studies; FAD synthase isoforms; SLC transporters; enzymes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The intra-cellular availability of vitamin-derived cofactors is strictly required for the correct structure and function of a great number of enzymes in all living organisms. Nevertheless, many aspects concerning vitamins and/or their derived cofactor absorption, transport, metabolism and intracellular trafficking are still awaiting elucidation, as well as the mode of insertion of cofactors into nascent polypeptides. Given the relevance of these essential molecules for cellular functionality, it is not surprising that a number of severe human pathological conditions, such as cancer, neurodegeneration and certain inborn errors of metabolism, are related to alterations to cofactor availability; therefore, further research is necessary to define the molecular consequences of alterations to the individual steps of cofactor delivery to search for a possible therapeutic intervention on the related pathologies.

This Special Issue aims to provide a sort of compendium on the recent advances in the fields of enzymology, cellular biochemistry and molecular biology related to vitamins and their derived cofactors. Considering the wide spectrum of functions that cofactor-requiring enzymes can have in cells, the translation of basic knowledge to pharmacology and pathophysiology will also be addressed.

Prof. Dr. Maria Barile
Prof. Michele Galluccio
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • vitamin
  • cofactor
  • transporter
  • assembly
  • vitamin-responsive inborn errors of metabolism

Published Papers (4 papers)

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Research

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11 pages, 1453 KiB  
Article
Exploring the Roles of Vitamins C and D and Etifoxine in Combination with Citalopram in Depression/Anxiety Model: A Focus on ICAM-1, SIRT1 and Nitric Oxide
by Omar Gammoh, Aseel Ibrahim, Ala Yehya, Abdelrahim Alqudah, Esam Qnais, Sara Altaber, Osama Abo Alrob, Alaa A. A. Aljabali and Murtaza M. Tambuwala
Int. J. Mol. Sci. 2024, 25(4), 1960; https://doi.org/10.3390/ijms25041960 - 06 Feb 2024
Viewed by 680
Abstract
The study of intercellular adhesion molecule-1 (ICAM-1) and SIRT1, a member of the sirtuin family with nitric oxide (NO), is emerging in depression and anxiety. As with all antidepressants, the efficacy is delayed and inconsistent. Ascorbic acid (AA) and vitamin D (D) showed [...] Read more.
The study of intercellular adhesion molecule-1 (ICAM-1) and SIRT1, a member of the sirtuin family with nitric oxide (NO), is emerging in depression and anxiety. As with all antidepressants, the efficacy is delayed and inconsistent. Ascorbic acid (AA) and vitamin D (D) showed antidepressant properties, while etifoxine (Etx), a GABAA agonist, alleviates anxiety symptoms. The present study aimed to investigate the potential augmentation of citalopram using AA, D and Etx and related the antidepressant effect to brain and serum ICAM-1, SIRT1 and NO in an animal model. BALB/c mice were divided into naive, control, citalopram, citalopram + etx, citalopram + AA, citalopram + D and citalopram + etx + AA + D for 7 days. On the 8th day, the mice were restrained for 8 h, followed by a forced swim test and marble burying test before scarification. Whole-brain and serum expression of ICAM-1, Sirt1 and NO were determined. Citalopram’s antidepressant and sedative effects were potentiated by ascorbic acid, vitamin D and etifoxine alone and in combination (p < 0.05), as shown by the decreased floating time and rearing frequency. Brain NO increased significantly (p < 0.05) in depression and anxiety and was associated with an ICAM-1 increase versus naive (p < 0.05) and a Sirt1 decrease (p < 0.05) versus naive. Both ICAM-1 and Sirt1 were modulated by antidepressants through a non-NO-dependent pathway. Serum NO expression was unrelated to serum ICAM-1 and Sirt1. Brain ICAM-1, Sirt1 and NO are implicated in depression and are modulated by antidepressants. Full article
(This article belongs to the Special Issue Vitamins and Derived Cofactors: Transport, Metabolism, Assembly and Deficiencies)
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Review

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23 pages, 5517 KiB  
Review
Pyridoxal 5′-Phosphate Biosynthesis by Pyridox-(am)-ine 5′-Phosphate Oxidase: Species-Specific Features
by Maribel Rivero, Nerea Novo and Milagros Medina
Int. J. Mol. Sci. 2024, 25(6), 3174; https://doi.org/10.3390/ijms25063174 - 09 Mar 2024
Viewed by 734
Abstract
Enzymes reliant on pyridoxal 5′-phosphate (PLP), the metabolically active form of vitamin B6, hold significant importance in both biology and medicine. They facilitate various biochemical reactions, particularly in amino acid and neurotransmitter metabolisms. Vitamin B6 is absorbed by organisms in [...] Read more.
Enzymes reliant on pyridoxal 5′-phosphate (PLP), the metabolically active form of vitamin B6, hold significant importance in both biology and medicine. They facilitate various biochemical reactions, particularly in amino acid and neurotransmitter metabolisms. Vitamin B6 is absorbed by organisms in its non-phosphorylated form and phosphorylated within cells via pyridoxal kinase (PLK) and pyridox-(am)-ine 5′-phosphate oxidase (PNPOx). The flavin mononucleotide-dependent PNPOx enzyme converts pyridoxine 5′-phosphate and pyridoxamine 5′-phosphate into PLP. PNPOx is vital for both biosynthesis and salvage pathways in organisms producing B6 vitamers. However, for those depending on vitamin B6 as a nutrient, PNPOx participates only in the salvage pathway. Transferring the PLP produced via PNPOx to client apo-enzymes is indispensable for their catalytic function, proper folding and targeting of specific organelles. PNPOx activity deficiencies due to inborn errors lead to severe neurological pathologies, particularly neonatal epileptic encephalopathy. PNPOx maintains PLP homeostasis through highly regulated mechanisms, including structural alterations throughout the catalytic cycle and allosteric PLP binding, influencing substrate transformation at the active site. Elucidation at the molecular level of the mechanisms underlying PNPOx activity deficiencies is a requirement to develop personalized approaches to treat related disorders. Finally, despite shared features, the few PNPOx enzymes molecularly and functionally studied show species-specific regulatory properties that open the possibility of targeting it in pathogenic organisms. Full article
(This article belongs to the Special Issue Vitamins and Derived Cofactors: Transport, Metabolism, Assembly and Deficiencies)
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21 pages, 1910 KiB  
Review
The Potential Use of Vitamin D3 and Phytochemicals for Their Anti-Ageing Effects
by Kazuki Santa, Yoshio Kumazawa, Kenji Watanabe and Isao Nagaoka
Int. J. Mol. Sci. 2024, 25(4), 2125; https://doi.org/10.3390/ijms25042125 - 09 Feb 2024
Viewed by 2823
Abstract
Unlike other vitamins, vitamin D3 is synthesised in skin cells in the body. Vitamin D3 has been known as a bone-related hormone. Recently, however, it has been considered as an immune vitamin. Vitamin D3 deficiency influences the onset of a variety of diseases. [...] Read more.
Unlike other vitamins, vitamin D3 is synthesised in skin cells in the body. Vitamin D3 has been known as a bone-related hormone. Recently, however, it has been considered as an immune vitamin. Vitamin D3 deficiency influences the onset of a variety of diseases. Vitamin D3 regulates the production of proinflammatory cytokines such as tumour necrosis factor-α (TNF-α) through binding to vitamin D receptors (VDRs) in immune cells. Since blood levels of vitamin D3 (25-OH-D3) were low in coronavirus disease 2019 (COVID-19) patients, there has been growing interest in the importance of vitamin D3 to maintaining a healthy condition. On the other hand, phytochemicals are compounds derived from plants with over 7000 varieties and have various biological activities. They mainly have health-promoting effects and are classified as terpenoids, carotenoids, flavonoids, etc. Flavonoids are known as the anti-inflammatory compounds that control TNF-α production. Chronic inflammation is induced by the continuous production of TNF-α and is the fundamental cause of diseases like obesity, dyslipidaemia, diabetes, heart and brain diseases, autoimmune diseases, Alzheimer’s disease, and cancer. In addition, the ageing process is induced by chronic inflammation. This review explains the cooperative effects of vitamin D3 and phytochemicals in the suppression of inflammatory responses, how it balances the natural immune response, and its link to anti-ageing effects. In addition, vitamin D3 and phytochemicals synergistically contribute to anti-ageing by working with ageing-related genes. Furthermore, prevention of ageing processes induced by the chronic inflammation requires the maintenance of healthy gut microbiota, which is related to daily dietary habits. In this regard, supplementation of vitamin D3 and phytochemicals plays an important role. Recently, the association of the prevention of the non-disease condition called “ME-BYO” with the maintenance of a healthy condition has been an attractive regimen, and the anti-ageing effect discussed here is important for a healthy and long life. Full article
(This article belongs to the Special Issue Vitamins and Derived Cofactors: Transport, Metabolism, Assembly and Deficiencies)
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22 pages, 715 KiB  
Review
Micronutrient Deficiency in Inherited Metabolic Disorders Requiring Diet Regimen: A Brief Critical Review
by Albina Tummolo, Rosa Carella, Donatella De Giovanni, Giulia Paterno, Simonetta Simonetti, Maria Tolomeo, Piero Leone and Maria Barile
Int. J. Mol. Sci. 2023, 24(23), 17024; https://doi.org/10.3390/ijms242317024 - 30 Nov 2023
Viewed by 1131
Abstract
Many inherited metabolic disorders (IMDs), including disorders of amino acid, fatty acid, and carbohydrate metabolism, are treated with a dietary reduction or exclusion of certain macronutrients, putting one at risk of a reduced intake of micronutrients. In this review, we aim to provide [...] Read more.
Many inherited metabolic disorders (IMDs), including disorders of amino acid, fatty acid, and carbohydrate metabolism, are treated with a dietary reduction or exclusion of certain macronutrients, putting one at risk of a reduced intake of micronutrients. In this review, we aim to provide available evidence on the most common micronutrient deficits related to specific dietary approaches and on the management of their deficiency, in the meanwhile discussing the main critical points of each nutritional supplementation. The emerging concepts are that a great heterogeneity in clinical practice exists, as well as no univocal evidence on the most common micronutrient abnormalities. In phenylketonuria, for example, micronutrients are recommended to be supplemented through protein substitutes; however, not all formulas are equally supplemented and some of them are not added with micronutrients. Data on pyridoxine and riboflavin status in these patients are particularly scarce. In long-chain fatty acid oxidation disorders, no specific recommendations on micronutrient supplementation are available. Regarding carbohydrate metabolism disorders, the difficult-to-ascertain sugar content in supplementation formulas is still a matter of concern. A ketogenic diet may predispose one to both oligoelement deficits and their overload, and therefore deserves specific formulations. In conclusion, our overview points out the lack of unanimous approaches to micronutrient deficiencies, the need for specific formulations for IMDs, and the necessity of high-quality studies, particularly for some under-investigated deficits. Full article
(This article belongs to the Special Issue Vitamins and Derived Cofactors: Transport, Metabolism, Assembly and Deficiencies)
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