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Keywords = vitamin K vitamers

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46 pages, 3846 KB  
Review
Complexes of Fat-Soluble Vitamins with Cyclodextrins
by Monika Zielińska-Pisklak, Konrad Adam Michalik and Łukasz Szeleszczuk
Int. J. Mol. Sci. 2025, 26(13), 6110; https://doi.org/10.3390/ijms26136110 - 25 Jun 2025
Cited by 1 | Viewed by 2776
Abstract
Vitamins are chemical compounds, or a group of closely related compounds known as vitamers, which are crucial for an organism’s metabolic functions. Vitamins are categorized as either water-soluble or fat-soluble, with this second group composed of vitamins A, D, E, and K. The [...] Read more.
Vitamins are chemical compounds, or a group of closely related compounds known as vitamers, which are crucial for an organism’s metabolic functions. Vitamins are categorized as either water-soluble or fat-soluble, with this second group composed of vitamins A, D, E, and K. The low aqueous solubility of these compounds often necessitates the use of pharmaceutical excipients to benefit from their medicinal efficiency. A successful example of this is the formation of the inclusion complexes with cyclodextrins (CDs), a group of cyclic oligosaccharides, composed of glucose subunits forming a macrocyclic ring. CD complexes with fat-soluble vitamins have been consistently utilized to accomplish diverse objectives, with CDs predominantly employed as solubilizers and absorption enhancers. This article examines studies detailing the synthesis and the biological, physicochemical, and structural characteristics of the inclusion complexes formed between fat-soluble vitamins and different cyclodextrins. This research demonstrates that although the fat-soluble vitamins form stable complexes with various CDs, the kind of CDs employed significantly influences the resultant properties of the complex formed. Full article
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22 pages, 919 KB  
Review
Vitamin K Properties in Stroke and Alzheimer’s Disease: A Janus Bifrons in Protection and Prevention
by Lorenzo Grimaldi, Rosaria A. Cavallaro, Domenico De Angelis, Andrea Fuso and Giulia Sancesario
Molecules 2025, 30(5), 1027; https://doi.org/10.3390/molecules30051027 - 24 Feb 2025
Cited by 4 | Viewed by 10795
Abstract
Vitamin K is essential for many physiological processes, including coagulation, bone metabolism, tissue calcification, and antioxidant activity. Vitamin K vitamers are represented by lipophilic compounds with similar chemical structure (i.e., phylloquinone (vitamin K1) and menaquinone (vitamin K2)). Vitamin K deficiency can affect coagulation [...] Read more.
Vitamin K is essential for many physiological processes, including coagulation, bone metabolism, tissue calcification, and antioxidant activity. Vitamin K vitamers are represented by lipophilic compounds with similar chemical structure (i.e., phylloquinone (vitamin K1) and menaquinone (vitamin K2)). Vitamin K deficiency can affect coagulation and vascular calcification, increasing the risk of hemorrhages, atherosclerosis, cerebrovascular diseases, and neurodegeneration. Recently, several studies have hypothesized a possible dual role of vitamin K vitamers in benefiting both vascular and cerebral health, e.g., by sphingolipids biosynthesis or ferroptosis inhibition. The aim of this narrative review is to deepen the understanding of biological activities of vitamin K and its possible dual protective/preventive actions in neurovascular and degenerative conditions, e.g., stroke and dementia. Given the difficulties related to hemorrhagic risk entailed in the prevention of strokes, the function of vitamin K antagonists is also investigated. Finally, we track the development of a clinical concept for a future preventive strategy and innovative use of vitamin K as a supplement to counteract neurovascular and pathological processes, focusing in particular on stroke and dementia. Full article
(This article belongs to the Special Issue The Design, Synthesis, and Biological Activity of New Drug Candidates)
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19 pages, 2361 KB  
Article
Nannochloropsis oceanica as a Source of Bioactive Compounds: Mapping the Effects of Cultivation Conditions on Biomass Productivity and Composition Using Response Surface Methodology
by Emil Gundersen, Jette Jakobsen, Susan Løvstad Holdt and Charlotte Jacobsen
Mar. Drugs 2024, 22(11), 505; https://doi.org/10.3390/md22110505 - 6 Nov 2024
Cited by 8 | Viewed by 5309
Abstract
Microalga Nannochloropsis oceanica presents a promising source of high-value food ingredients such as protein, omega-3 fatty acids, and vitamins. To fully unlock its potential, a thorough understanding of how cultivation conditions affect both growth and the nutritional composition is required. Hence, this study [...] Read more.
Microalga Nannochloropsis oceanica presents a promising source of high-value food ingredients such as protein, omega-3 fatty acids, and vitamins. To fully unlock its potential, a thorough understanding of how cultivation conditions affect both growth and the nutritional composition is required. Hence, this study aimed to test and model the effects of temperature, light intensity, and salinity on biomass productivity and the final contents of protein, eicosapentaenoic acid (EPA), and vitamin K2 using response surface methodology (RSM). The RSM experiment revealed that the highest temperature and light intensity tested favored biomass productivity and protein content. According to the generated models, the two responses peaked with 0.135 g DM·L−1·day−1 and 0.559 g·g−1 DM, respectively, at 27 °C and 300–350 µmol·m−2·s−1. In contrast, the contents of both EPA and menaquinone-4 (MK-4), the only detected K vitamer, were stimulated at the lowest tested temperature. Based on the generated models, the two responses peaked with 0.037 g·g−1 DM and 89.3 µg·g−1 DM, respectively, at 19 °C combined with 3.0% salinity (EPA) or 120 µmol·m−2·s−1 (MK-4). Although additional optima may exist beyond the tested conditions, these findings provide valuable information on N. oceanica’s cellular response to changes in key cultivation conditions. Furthermore, it shows that two-stage cultivation may be needed to fully unlock the potential of this microalga as a future source of valuable lipid ingredients. Full article
(This article belongs to the Special Issue High-Value Algae Products)
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15 pages, 1315 KB  
Article
Quantitative Study of Vitamin K in Plants by Pressurized Liquid Extraction and LC-MS/MS
by Iryna Bryshten, Łukasz Paprotny, Małgorzata Olszowy-Tomczyk and Dorota Wianowska
Molecules 2024, 29(18), 4420; https://doi.org/10.3390/molecules29184420 - 17 Sep 2024
Cited by 2 | Viewed by 3128
Abstract
The health-promoting properties of vitamin K stimulate the growing interest in this compound, which translates into the development of new analytical methodologies for its determination. New, more efficient methods of its isolation are sought, paying increasingly more attention to the methods within currently [...] Read more.
The health-promoting properties of vitamin K stimulate the growing interest in this compound, which translates into the development of new analytical methodologies for its determination. New, more efficient methods of its isolation are sought, paying increasingly more attention to the methods within currently available extraction techniques that, owing to the optimization of the process, not only increase the extraction efficiency but are also economical and environmentally friendly. This article proposes a procedure for the extraction and analysis of one of the vitamin K vitamers, i.e., vitamin K1, using PLE and LC-MS/MS. It has been shown that the PLE technique can be optimized with a mathematical model—accelerating and reducing the costs of the extraction process—which, together with process automation, bodes well for industrial applications. The optimized process was used to extract vitamin K1 from various vegetables, showing very different contents of the test compound ranging from 1.22 to 114.30 µg/g dry weight for avocado and spinach, respectively. In addition, by showing the effect of water within the material subjected to extraction on the variable yield of vitamin K1, attention was drawn to the need to standardize the analytical methods used in assessing the quality of food products. Full article
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18 pages, 3612 KB  
Article
Amyloidogenic and Neuroinflammatory Molecular Pathways Are Contrasted Using Menaquinone 4 (MK4) and Reduced Menaquinone 7 (MK7R) in Association with Increased DNA Methylation in SK-N-BE Neuroblastoma Cell Line
by Michela Orticello, Rosaria A. Cavallaro, Daniele Antinori, Tiziana Raia, Marco Lucarelli and Andrea Fuso
Cells 2024, 13(1), 58; https://doi.org/10.3390/cells13010058 - 27 Dec 2023
Cited by 6 | Viewed by 4328
Abstract
Besides its role in coagulation, vitamin K seems to be involved in various other mechanisms, including inflammation and age-related diseases, also at the level of gene expression. This work examined the roles of two vitamin K2 (menaquinones) vitamers, namely, menaquinone-4 (MK4) and reduced [...] Read more.
Besides its role in coagulation, vitamin K seems to be involved in various other mechanisms, including inflammation and age-related diseases, also at the level of gene expression. This work examined the roles of two vitamin K2 (menaquinones) vitamers, namely, menaquinone-4 (MK4) and reduced menaquinone-7 (MK7R), as gene modulator compounds, as well as their potential role in the epigenetic regulation of genes involved in amyloidogenesis and neuroinflammation. The SK-N-BE human neuroblastoma cells provided a “first-line” model for screening the neuroinflammatory and neurodegenerative molecular pathways. MK7R, being a new vitamin K form, was first tested in terms of solubilization, uptake and cell viability, together with MK4 as an endogenous control. We assessed the expression of key factors in amyloidogenesis and neuroinflammation, observing that the MK7R treatment was associated with the downregulation of neurodegeneration- (PSEN1 and BACE1) and neuroinflammation- (IL-1β and IL-6) associated genes, whereas genes retaining protective roles toward amiloidogenesis were upregulated (ADAM10 and ADAM17). By profiling the DNA methylation patterns of genes known to be epigenetically regulated, we observed a correlation between hypermethylation and the downregulation of PSEN1, IL-1β and IL-6. These results suggest a possible role of MK7R in the treatment of cognitive impairment, giving a possible base for further preclinical experiments in animal models of neurodegenerative disease. Full article
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16 pages, 1584 KB  
Article
Development, Validation, and Two-Year Application of Rapid and Simple LC-MS/MS-Based Method for the Determination of K2MK-7 in Blood Samples
by Łukasz Paprotny, Dorota Szewczak, Iryna Bryshten and Dorota Wianowska
Molecules 2023, 28(18), 6523; https://doi.org/10.3390/molecules28186523 - 8 Sep 2023
Cited by 4 | Viewed by 2702
Abstract
Biological properties of menaquinone-7, one of the vitamin K2 vitamers (K2MK-7), both those proven and those that remain to be investigated, arouse extensive interest that goes beyond the strictly scientific framework. The most important of them is the prevention of age-related diseases, considering [...] Read more.
Biological properties of menaquinone-7, one of the vitamin K2 vitamers (K2MK-7), both those proven and those that remain to be investigated, arouse extensive interest that goes beyond the strictly scientific framework. The most important of them is the prevention of age-related diseases, considering that we live in the times identified as the era of aging societies and many people are exposed to the vitamin K2MK-7 deficiency. Therefore, an effective analytical protocol that can be adopted as a diagnostic and preventive analytics tool is needed. Herein, a simple sample preparation method followed by the liquid chromatography-tandem mass spectrometry-based method (LC-MS/MS), was used for the selective and sensitive determination of K2MK-7 in serum samples. Under the optimized conditions, using 500 µL of serum and the same amount of n-hexane, the reproducibility and the accuracy were obtained in the ranges of 89–97% and 86–110%, respectively, and the limit of detection value was 0.01 ng/mL. This method was used for the routine analysis. Statistical interpretation of the data from 518 samples obtained during 2 years of practice allowed for obtaining information on the content and distribution of K2MK-7 in the Polish population, broken down by the sex and age groups. Full article
(This article belongs to the Special Issue Chromatography—The Ultimate Analytical Tool II)
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16 pages, 1626 KB  
Review
Role of Vitamin K in Chronic Kidney Disease: A Focus on Bone and Cardiovascular Health
by Federica Bellone, Maria Cinquegrani, Ramona Nicotera, Nazareno Carullo, Alessandro Casarella, Pierangela Presta, Michele Andreucci, Giovanni Squadrito, Giuseppe Mandraffino, Marcello Prunestì, Cristina Vocca, Giovambattista De Sarro, Davide Bolignano and Giuseppe Coppolino
Int. J. Mol. Sci. 2022, 23(9), 5282; https://doi.org/10.3390/ijms23095282 - 9 May 2022
Cited by 27 | Viewed by 15504
Abstract
Chronic kidney disease (CKD) is commonly associated with vitamin K deficiency. Some of the serious complications of CKD are represented by cardiovascular disease (CVD) and skeletal fragility with an increased risk of morbidity and mortality. A complex pathogenetic link between hormonal and ionic [...] Read more.
Chronic kidney disease (CKD) is commonly associated with vitamin K deficiency. Some of the serious complications of CKD are represented by cardiovascular disease (CVD) and skeletal fragility with an increased risk of morbidity and mortality. A complex pathogenetic link between hormonal and ionic disturbances, bone tissue and metabolism alterations, and vascular calcification (VC) exists and has been defined as chronic kidney disease–mineral and bone disorder (CKD-MBD). Poor vitamin K status seems to have a key role in the progression of CKD, but also in the onset and advance of both bone and cardiovascular complications. Three forms of vitamin K are currently known: vitamin K1 (phylloquinone), vitamin K2 (menaquinone), and vitamin K3 (menadione). Vitamin K plays different roles, including in activating vitamin K-dependent proteins (VKDPs) and in modulating bone metabolism and contributing to the inhibition of VC. This review focuses on the biochemical and functional characteristics of vitamin K vitamers, suggesting this nutrient as a possible marker of kidney, CV, and bone damage in the CKD population and exploring its potential use for promoting health in this clinical setting. Treatment strategies for CKD-associated osteoporosis and CV disease should include vitamin K supplementation. However, further randomized clinical studies are needed to assess the safety and the adequate dosage to prevent these CKD complications. Full article
(This article belongs to the Collection State-of-the-Art Bioactives and Nutraceuticals in Italy)
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12 pages, 1493 KB  
Article
Content and Bioaccessibility of Vitamin K (Phylloquinone and Menaquinones) in Cheese
by Marie Bagge Jensen, Andrius Daugintis and Jette Jakobsen
Foods 2021, 10(12), 2938; https://doi.org/10.3390/foods10122938 - 29 Nov 2021
Cited by 11 | Viewed by 4961
Abstract
Vitamin K is a fat-soluble group of vitamers consisting of phylloquinone (PK) and menaquinones (MKs). To date, only a daily reference intake for PK is set; however, in the last decade, research studying the correlation between MKs intake and improvement of health in [...] Read more.
Vitamin K is a fat-soluble group of vitamers consisting of phylloquinone (PK) and menaquinones (MKs). To date, only a daily reference intake for PK is set; however, in the last decade, research studying the correlation between MKs intake and improvement of health in regards to cardiovascular diseases, bone metabolism, and chronic kidney disease has been conducted. MKs are synthesised by bacteria in the fermentation process of foods, e.g., cheeses. The content and bioaccessibility of vitamin K vitamers (PK, MK-4, MK-5, MK-6, MK-7, MK-8, MK-9, and MK-10) were assessed in eight different cheese products differing in ripening time, starter culture, fat content, and water content. The bioaccessibility was assessed using the static in vitro digestion model INFOGEST 2.0. Variation of the vitamin K content (<0.5 μg/100 g–32 μg/100 g) and of the vitamin K bioaccessibility (6.4–80%) was observed. A longer ripening time did not necessarily result in an increase of MKs. These results indicate that the vitamin K content and bioaccessibility differs significantly between different cheese products, and the ripening time, starter culture, fat content, and water content cannot explain this difference. Full article
(This article belongs to the Section Food Nutrition)
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37 pages, 677 KB  
Review
Vitamin E beyond Its Antioxidant Label
by Anca Ungurianu, Anca Zanfirescu, Georgiana Nițulescu and Denisa Margină
Antioxidants 2021, 10(5), 634; https://doi.org/10.3390/antiox10050634 - 21 Apr 2021
Cited by 113 | Viewed by 20933
Abstract
Vitamin E, comprising tocopherols and tocotrienols, is mainly known as an antioxidant. The aim of this review is to summarize the molecular mechanisms and signaling pathways linked to inflammation and malignancy modulated by its vitamers. Preclinical reports highlighted a myriad of cellular effects [...] Read more.
Vitamin E, comprising tocopherols and tocotrienols, is mainly known as an antioxidant. The aim of this review is to summarize the molecular mechanisms and signaling pathways linked to inflammation and malignancy modulated by its vitamers. Preclinical reports highlighted a myriad of cellular effects like modulating the synthesis of pro-inflammatory molecules and oxidative stress response, inhibiting the NF-κB pathway, regulating cell cycle, and apoptosis. Furthermore, animal-based models have shown that these molecules affect the activity of various enzymes and signaling pathways, such as MAPK, PI3K/Akt/mTOR, JAK/STAT, and NF-κB, acting as the underlying mechanisms of their reported anti-inflammatory, neuroprotective, and anti-cancer effects. In clinical settings, not all of these were proven, with reports varying considerably. Nonetheless, vitamin E was shown to improve redox and inflammatory status in healthy, diabetic, and metabolic syndrome subjects. The anti-cancer effects were inconsistent, with both pro- and anti-malignant being reported. Regarding its neuroprotective properties, several studies have shown protective effects suggesting vitamin E as a potential prevention and therapeutic (as adjuvant) tool. However, source and dosage greatly influence the observed effects, with bioavailability seemingly a key factor in obtaining the preferred outcome. We conclude that this group of molecules presents exciting potential for the prevention and treatment of diseases with an inflammatory, redox, or malignant component. Full article
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26 pages, 2169 KB  
Review
Vitamin K in Vertebrates’ Reproduction: Further Puzzling Pieces of Evidence from Teleost Fish Species
by Silvia Beato, Francisco Javier Toledo-Solís and Ignacio Fernández
Biomolecules 2020, 10(9), 1303; https://doi.org/10.3390/biom10091303 - 9 Sep 2020
Cited by 12 | Viewed by 6668
Abstract
Vitamin K (VK) is a fat-soluble vitamin that vertebrates have to acquire from the diet, since they are not able to de novo synthesize it. VK has been historically known to be required for the control of blood coagulation, and more recently, bone [...] Read more.
Vitamin K (VK) is a fat-soluble vitamin that vertebrates have to acquire from the diet, since they are not able to de novo synthesize it. VK has been historically known to be required for the control of blood coagulation, and more recently, bone development and homeostasis. Our understanding of the VK metabolism and the VK-related molecular pathways has been also increased, and the two main VK-related pathways—the pregnane X receptor (PXR) transactivation and the co-factor role on the γ-glutamyl carboxylation of the VK dependent proteins—have been thoroughly investigated during the last decades. Although several studies evidenced how VK may have a broader VK biological function than previously thought, including the reproduction, little is known about the specific molecular pathways. In vertebrates, sex differentiation and gametogenesis are tightly regulated processes through a highly complex molecular, cellular and tissue crosstalk. Here, VK metabolism and related pathways, as well as how gametogenesis might be impacted by VK nutritional status, will be reviewed. Critical knowledge gaps and future perspectives on how the different VK-related pathways come into play on vertebrate’s reproduction will be identified and proposed. The present review will pave the research progress to warrant a successful reproductive status through VK nutritional interventions as well as towards the establishment of reliable biomarkers for determining proper nutritional VK status in vertebrates. Full article
(This article belongs to the Special Issue Relevant Biomolecules for Germ Cells and Fertilization)
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13 pages, 568 KB  
Review
Vitamin K and Kidney Transplantation
by Maria Fusaro, Laura Cosmai, Pieter Evenepoel, Thomas L. Nickolas, Angela M. Cheung, Andrea Aghi, Giovanni Tripepi, Mario Plebani, Giorgio Iervasi, Roberto Vettor, Martina Zaninotto, Maura Ravera, Marina Foramitti, Sandro Giannini, Stefania Sella and Maurizio Gallieni
Nutrients 2020, 12(9), 2717; https://doi.org/10.3390/nu12092717 - 5 Sep 2020
Cited by 10 | Viewed by 4763
Abstract
The assessment of the vitamin K status and its effects on clinical outcomes in kidney transplantation (KT) patients has sparked interest, but it is still largely unfulfilled. In part, this is due to difficulties in laboratory measurements of vitamin K, especially K2 vitamers. [...] Read more.
The assessment of the vitamin K status and its effects on clinical outcomes in kidney transplantation (KT) patients has sparked interest, but it is still largely unfulfilled. In part, this is due to difficulties in laboratory measurements of vitamin K, especially K2 vitamers. Vitamin K status is currently best assessed by measuring undercarboxylated vitamin-K-dependent proteins. The relative contribution of vitamin K1 and K2 to the health status of the general population and CKD (chronic kidney disease) patients, including KT patients, is also poorly studied. Through a complete and first review of the existing literature, we summarize the current knowledge of vitamin K pathophysiology and its potential role in preventing KT complications and improving organ survival. A specific focus is placed on cardiovascular complications, bone fractures, and the relationship between vitamin K and cancer. Vitamin K deficiency could determine adverse outcomes, and KT patients should be better studied for vitamin K assessment and modalities of effective therapeutic approaches. Full article
(This article belongs to the Special Issue Physiology and Pathology of Vitamin K Intake)
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24 pages, 602 KB  
Review
Vitamin K as a Diet Supplement with Impact in Human Health: Current Evidence in Age-Related Diseases
by Dina C. Simes, Carla S. B. Viegas, Nuna Araújo and Catarina Marreiros
Nutrients 2020, 12(1), 138; https://doi.org/10.3390/nu12010138 - 3 Jan 2020
Cited by 153 | Viewed by 31370
Abstract
Vitamin K health benefits have been recently widely shown to extend beyond blood homeostasis and implicated in chronic low-grade inflammatory diseases such as cardiovascular disease, osteoarthritis, dementia, cognitive impairment, mobility disability, and frailty. Novel and more efficient nutritional and therapeutic options are urgently [...] Read more.
Vitamin K health benefits have been recently widely shown to extend beyond blood homeostasis and implicated in chronic low-grade inflammatory diseases such as cardiovascular disease, osteoarthritis, dementia, cognitive impairment, mobility disability, and frailty. Novel and more efficient nutritional and therapeutic options are urgently needed to lower the burden and the associated health care costs of these age-related diseases. Naturally occurring vitamin K comprise the phylloquinone (vitamin K1), and a series of menaquinones broadly designated as vitamin K2 that differ in source, absorption rates, tissue distribution, bioavailability, and target activity. Although vitamin K1 and K2 sources are mainly dietary, consumer preference for diet supplements is growing, especially when derived from marine resources. The aim of this review is to update the reader regarding the specific contribution and effect of each K1 and K2 vitamers in human health, identify potential methods for its sustainable and cost-efficient production, and novel natural sources of vitamin K and formulations to improve absorption and bioavailability. This new information will contribute to foster the use of vitamin K as a health-promoting supplement, which meets the increasing consumer demand. Simultaneously, relevant information on the clinical context and direct health consequences of vitamin K deficiency focusing in aging and age-related diseases will be discussed. Full article
(This article belongs to the Special Issue Nutraceutical, Nutrition Supplements and Human Health)
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21 pages, 1679 KB  
Article
Phylloquinone and Menaquinone-4 Tissue Distribution at Different Life Stages in Male and Female Sprague–Dawley Rats Fed Different VK Levels Since Weaning or Subjected to a 40% Calorie Restriction since Adulthood
by Guylaine Ferland, Isabelle Doucet and Dominique Mainville
Nutrients 2016, 8(3), 141; https://doi.org/10.3390/nu8030141 - 4 Mar 2016
Cited by 17 | Viewed by 8001
Abstract
Whether through the vitamin K-dependent proteins or the individual K vitamers, vitamin K (VK) is associated with a number of age-related conditions (e.g., osteoporosis, atherosclerosis, insulin resistance, cognitive decline). In light of this, we investigated the influence of lifetime dietary VK exposure on [...] Read more.
Whether through the vitamin K-dependent proteins or the individual K vitamers, vitamin K (VK) is associated with a number of age-related conditions (e.g., osteoporosis, atherosclerosis, insulin resistance, cognitive decline). In light of this, we investigated the influence of lifetime dietary VK exposure on the tissue distribution of phylloquinone (K1) and menaquinone-4 (MK-4) vitamers in 3-, 12- and 22-month-old male and female rats fed different K1 diets since weaning or subjected to a 40% calorie restricted diet (CR) since adulthood. Dietary K1 intakes around the minimal amount required for normal blood coagulation had no significant influence on body weights of both male and female rats at different life stages. Tissue contents of the K vitamers differed according to organs, were generally higher in females than in males, and increased with K1 intake. The MK-4/total VK ratios tended to be increased in old age possibly reflecting an increased physiological demand for MK-4 during aging. Our study also confirmed the greater susceptibility of male rats to low VK containing diet, notably at a younger age. Despite lifelong higher K1 intakes per unit body weight, tissue K1 and MK-4 contents at 20 months were generally lower in CR rats compared to their ad libitum (AL) counterparts. Whether the lower tissue MK-4 content is the result of lower synthesis from K1 or greater tissue utilization remains to be determined. However, the more youthful coagulation profile observed in old CR rats (vs. AL rats) tends to support the notion that CR is associated with greater utilization of the K vitamers to sustain physiological functions. Full article
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31 pages, 726 KB  
Review
VKORC1 and VKORC1L1: Why do Vertebrates Have Two Vitamin K 2,3-Epoxide Reductases?
by Johannes Oldenburg, Matthias Watzka and Carville G. Bevans
Nutrients 2015, 7(8), 6250-6280; https://doi.org/10.3390/nu7085280 - 30 Jul 2015
Cited by 26 | Viewed by 9451
Abstract
Among all cellular life on earth, with the exception of yeasts, fungi, and some prokaryotes, VKOR family homologs are ubiquitously encoded in nuclear genomes, suggesting ancient and important biological roles for these enzymes. Despite single gene and whole genome duplications on the largest [...] Read more.
Among all cellular life on earth, with the exception of yeasts, fungi, and some prokaryotes, VKOR family homologs are ubiquitously encoded in nuclear genomes, suggesting ancient and important biological roles for these enzymes. Despite single gene and whole genome duplications on the largest evolutionary timescales, and the fact that most gene duplications eventually result in loss of one copy, it is surprising that all jawed vertebrates (gnathostomes) have retained two paralogous VKOR genes. Both VKOR paralogs function as entry points for nutritionally acquired and recycled K vitamers in the vitamin K cycle. Here we present phylogenetic evidence that the human paralogs likely arose earlier than gnathostomes, possibly in the ancestor of crown chordates. We ask why gnathostomes have maintained these paralogs throughout evolution and present a current summary of what we know. In particular, we look to published studies about tissue- and developmental stage-specific expression, enzymatic function, phylogeny, biological roles and associated pathways that together suggest subfunctionalization as a major influence in evolutionary fixation of both paralogs. Additionally, we investigate on what evolutionary timescale the paralogs arose and under what circumstances in order to gain insight into the biological raison d’être for both VKOR paralogs in gnathostomes. Full article
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