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Phytochemistry Mar 2023Hydrogen stable isotope analyses (δH) of plant derived organic compounds are a useful tool for ecological, environmental, and palaeoclimatological research. However,...
Hydrogen stable isotope analyses (δH) of plant derived organic compounds are a useful tool for ecological, environmental, and palaeoclimatological research. However, during organic compound synthesis, variable biosynthetic H-fractionation has been suggested to occur as a result of changes in plant carbon fluxes. So far, inference has been based on examining the δH patterns of plant compounds along environmental gradients, among plant species, and between plant organs. In an alternative approach, we used four plant species with four different types of mutations that cause impaired starch synthesis to assess whether variability in carbon metabolism affects the biosynthetic H-fractionation during cellulose, phytol, and acetogenic lipid synthesis. We found that mutants with impaired starch synthesis always had higher cellulose and phytol δH values compared to the wild type. By contrast, H-fractionation during acetogenic lipid biosynthesis generally did not show strong metabolic sensitivity. We rationalise these differences by considering the biosynthetic pathway of each compound and the likely source of the variable isotope fractionation. In different organic compounds, the sensitivity of variable biosynthetic H-fractionation to changes in C-metabolism depends on incorporation of specific H atoms from precursor molecules. As such, we determined that the similar increase in cellulose and phytol δH values as an effect of impaired starch synthesis most likely originates in triose-phosphates.
Topics: Hydrogen; Carbon; Isotopes; Plants; Organic Chemicals; Cellulose; Lipids; Starch; Phytol; Carbon Isotopes; Plant Leaves
PubMed: 36528118
DOI: 10.1016/j.phytochem.2022.113563 -
Wiener Klinische Wochenschrift May 2018Vitamin K2 (VK2) belongs to the vitamin K family and comprises a number of subtypes differing in length of side chains consisting of isoprenoid groups (menaquinone-n,...
BACKGROUND
Vitamin K2 (VK2) belongs to the vitamin K family and comprises a number of subtypes differing in length of side chains consisting of isoprenoid groups (menaquinone-n, MK-n). It is essential for a number of physiological functions although the full spectrum of activity has not yet been elucidated. Due to its role in protection of mitochondrial damage, VK2 could be relevant in preventing disease progress in multiple sclerosis (MS).
METHODS
We measured VK2 serum levels by the double antibody sandwich Enzyme-linked Immunosorbent Assay (ELISA) technique in MS patients and age and sex matched controls, both under vitamin D supplementation, and related it to disease characteristics and treatment.
RESULTS
Overall, 45 MS patients (31 females and 39 of the relapsing-remitting type) and 29 healthy controls (19 females) were included in the analysis. The MS patients had vastly lower VK2 blood levels than controls (235 ± 100 ng/ml vs. 812 ± 154 ng/ml, respectively). Female patients had significantly lower VK2 levels than males and a decrease with age by approximately 10% per decade was found. The VK2 levels were lower with increasing numbers of attacks per year and were higher in patients with optic nerve lesions. No consistent relationship with medications was detected.
CONCLUSION
The substantially lower levels of VK2 in MS patients could be due to depletion, lower production in the gut, diminished absorption or, less likely, reduced intake of precursor vitamin K1. The role of VK2 in MS development and progress deserves further study.
Topics: Case-Control Studies; Cross-Sectional Studies; Female; Humans; Male; Multiple Sclerosis; Vitamin K; Vitamin K 2
PubMed: 29500722
DOI: 10.1007/s00508-018-1328-x -
Journal of Lipid Research Jan 2007Phytol, a branched-chain fatty alcohol, is the naturally occurring precursor of phytanic and pristanic acid, branched-chain fatty acids that are both ligands for the...
Phytol, a branched-chain fatty alcohol, is the naturally occurring precursor of phytanic and pristanic acid, branched-chain fatty acids that are both ligands for the nuclear hormone receptor peroxisome proliferator-activated receptor alpha (PPARalpha). To investigate the metabolism of phytol and the role of PPARalpha in its regulation, wild-type and PPARalpha knockout (PPARalpha-/-) mice were fed a phytol-enriched diet or, for comparison, a diet enriched with Wy-14,643, a synthetic PPARalpha agonist. After the phytol-enriched diet, phytol could only be detected in small intestine, the site of uptake, and liver. Upon longer duration of the diet, the level of the (E)-isomer of phytol increased significantly in the liver of PPARalpha-/- mice compared with wild-type mice. Activity measurements of the enzymes involved in phytol metabolism showed that treatment with a PPARalpha agonist resulted in a PPARalpha-dependent induction of at least two steps of the phytol degradation pathway in liver. Furthermore, the enzymes involved showed a higher activity toward the (E)-isomer than the (Z)-isomer of their respective substrates, indicating a stereospecificity toward the metabolism of (E)-phytol. In conclusion, the results described here show that the conversion of phytol to phytanic acid is regulated via PPARalpha and is specific for the breakdown of (E)-phytol.
Topics: Animals; Homeostasis; Immunoblotting; Mice; Mice, Knockout; PPAR alpha; Peroxisome Proliferators; Phytic Acid; Phytol; Pyrimidines; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 17015885
DOI: 10.1194/jlr.M600050-JLR200 -
PloS One 2013Since activation of PPARγ is the main target for the antidiabetic effect of TZDs, especially when it heterodimerizes with RXR, we aimed to test the potential...
Since activation of PPARγ is the main target for the antidiabetic effect of TZDs, especially when it heterodimerizes with RXR, we aimed to test the potential antidiabetic effect of phytol (250 mg/kg), the natural precursor of phytanic acid, a RXR ligand and/or pioglitazone (5 mg/kg) to diabetic insulin-resistant rats. Regarding the molecular docking simulation on PPARγ, phytanic acid, rather than phytol, showed a binding mode that mimics the crystal orientation of rosiglitazone and pioglitazone, forming H bonds with the same amino acids (S289, H 323, H 449 and Y 473), and the least energy level, which emphasizes their importance for PPARγ molecular recognition, activation, hence antidiabetic activity. In addition, docking on the RXRα/PPARγ heterodimer, revealed that phytanic acid has higher binding affinity and lesser energy score on RXRα, compared to the original ligand, retinoic acid. Phytanic acid binds by 3H bonds and shares retinoic acid in arginine (R 316). These results were further supported biochemically, where oral phytol and/or pioglitazone (5 mg/kg) improved significantly glucose homeostasis, lipid panel, raised serum adiponectin level and lowered TNF-α, reaching in most cases the effect of the 10 mg/kg pioglitazone. The study concluded that the insulin sensitizing/anti-diabetic effect of phytol is mediated by partly from activation of nuclear receptors and heterodimerization of RXR with PPARγ by phytanic acid.
Topics: Algorithms; Animals; Catalytic Domain; Crystallography, X-Ray; Dimerization; Hydrogen Bonding; Insulin Resistance; Ligands; Male; Molecular Docking Simulation; PPAR gamma; Phytanic Acid; Phytol; Protein Binding; Rats; Rats, Wistar; Retinoid X Receptor alpha; Software
PubMed: 23300941
DOI: 10.1371/journal.pone.0045638 -
Blood Aug 2020
Topics: Anticoagulants; Blood Coagulation Disorders; Hemorrhage; Humans; Pharmaceutical Preparations; Vitamin K
PubMed: 32790852
DOI: 10.1182/blood.2020006563 -
Brain Research Feb 2014Phytol, a branched chain unsaturated alcohol, is particularly interesting because it is an isolated compound from essential oils of different medicinal plants. The aim...
Phytol, a branched chain unsaturated alcohol, is particularly interesting because it is an isolated compound from essential oils of different medicinal plants. The aim of this study was to evaluate the anxiolytic-like effects of phytol in animal models to clarify their possible action mechanism. After acute intraperitoneal treatment with phytol at doses of 25, 50 and 75 mg/kg behavioral models of open-field, elevated-plus-maze, rota-rod, light-dark, marble-burying and pentobarbital sleeping time tests were utilized. In open field test, phytol (25, 50 and 75 mg/kg) [p<0.01] increased the number of crossings and rearings. However, the number of groomings [p<0.01] was reduced. Likewise, the number of entries and the time spent in light space were increased [p<0.01] while the number of marble-burying was decreased [p<0.001], in elevated-plus-maze, light-dark and marble-burying tests, respectively. In motor activity test, phytol (75 mg/kg) impaired the rota-rod performance of mice [p<0.01]. In pentobarbital sleeping time test, phytol 75 mg/kg decreased for latency of sleeping and phytol (25, 50 and 75 mg/kg) increased the sleep time when compared to negative control [p<0.05]. All these effects were reversed by pre-treatment with flumazenil (2.5mg/kg, i.p.), similarly to those observed with diazepam (2mg/kg, i.p.; positive control) suggesting that the phytol presents mechanism of action by interaction with the GABAergic system. These findings suggest that acute administration of phytol exerts an anxiolytic-like effect on mice. Furthermore, suppose that phytol interacts with GABAA receptor, probably at the receptor subtypes that mediate benzodiazepines effects, to produce sedative and anxiolytic activities.
Topics: Animals; Anti-Anxiety Agents; Behavior, Animal; Flumazenil; GABA Modulators; Male; Maze Learning; Mice; Motor Activity; Phytol; Sleep
PubMed: 24333358
DOI: 10.1016/j.brainres.2013.12.003 -
JMIR Public Health and Surveillance Feb 2022The fat-soluble K vitamins K1 and K2 play an essential role in the blood coagulation cascade and are made available predominantly through selective dietary intakes. They... (Observational Study)
Observational Study
BACKGROUND
The fat-soluble K vitamins K1 and K2 play an essential role in the blood coagulation cascade and are made available predominantly through selective dietary intakes. They are less known for their nonessential roles in a family of vitamin K-dependent proteins that promote various functions of organs and systems in the body. A lack of vitamin K can characterize vitamin and nutritional element insufficiency, which is different from a clinically apparent vitamin deficiency.
OBJECTIVE
This epidemiological study evaluated the nutritional status of vitamin K in a sample of the Indian population and vitamin K content in staple Indian foods.
METHODS
Serum levels of vitamin K1 and vitamin K2 in the form of menaquinone-7 (MK-7) were assessed via high-performance liquid chromatography coupled with fluorescence detection in 209 patients with type 2 diabetes, 50 healthy volunteers, and common staple foods in India.
RESULTS
After comparing populations with high and low serum vitamin K levels from various geographical regions, our results indicated that the sample of healthy Indian individuals and the sample of Indian patients with type 2 diabetes had low (insufficient) levels of vitamin K2 (MK-7; range 0.3-0.4 ng/mL). No significant differences existed in vitamin K1-related and MK-7-related values between healthy male and female subjects, between male and female subjects with diabetes, and between the healthy sample and the sample of patients with diabetes. The staple, commonly consumed Indian foods that were tested in this study had undetectable levels of vitamin K2, while levels of vitamin K1 varied widely (range 0-37 µg/100 g).
CONCLUSIONS
Based on our sample's low serum levels of vitamin K2 (MK-7) as well as the low levels of vitamin K2 in their typical diet, we propose that the general Indian population could benefit from the consumption of vitamin K2 in the form of MK-7 supplements.
TRIAL REGISTRATION
Clinical Trials Registry - India CTRI/2019/05/014246; http://ctri.nic.in/Clinicaltrials/showallp.php?mid1=21660&EncHid=&userName=014246; Clinical Trials Registry - India CTRI/2019/03/018278; http://ctri.nic.in/Clinicaltrials/showallp.php?mid1=32349&EncHid=&userName=018278.
Topics: Diabetes Mellitus, Type 2; Dietary Supplements; Female; Humans; Male; Vitamin K; Vitamin K 1; Vitamin K 2
PubMed: 35113033
DOI: 10.2196/31941 -
Nutrients Aug 2022The main function of vitamin K in the human organism is its activity in the blood clotting cascade. Epidemiological studies suggest that reduced intake of vitamin K may... (Review)
Review
The main function of vitamin K in the human organism is its activity in the blood clotting cascade. Epidemiological studies suggest that reduced intake of vitamin K may contribute to an increased risk of geriatric diseases such as atherosclerosis, dementia, osteoporosis, and osteoarthritis. A growing number of studies also indicate that vitamin K may be involved not only in preventing the development of certain cancers but it may also support classical cancer chemotherapy. This review article summarizes the results of studies on the anticancer effects of vitamin K on selected female malignancies, i.e., breast, cervical, and ovarian cancer, published over the past 20 years. The promising effects of vitamin K on cancer cells observed so far indicate its great potential, but also the need for expansion of our knowledge in this area by conducting extensive research, including clinical trials.
Topics: Aged; Blood Coagulation; Female; Humans; Neoplasms; Osteoporosis; Ovarian Neoplasms; Vitamin K; Vitamin K 1; Vitamin K 2
PubMed: 36014904
DOI: 10.3390/nu14163401 -
BioMed Research International 2018Bone is a metabolically active tissue that renews itself throughout one's life. Cytokines along with several hormonal, nutritional, and growth factors are involved in... (Review)
Review
Bone is a metabolically active tissue that renews itself throughout one's life. Cytokines along with several hormonal, nutritional, and growth factors are involved in tightly regulated bone remodeling. Accordingly, vitamin K as a multifunctional vitamin has been recently deemed appreciable as a topic of research as it plays a pivotal role in maintenance of the bone strength, and it has been proved to have a positive impact on the bone metabolism. Vitamin K exerts its anabolic effect on the bone turnover in different ways such as promoting osteoblast differentiation, upregulating transcription of specific genes in osteoblasts, and activating the bone-associated vitamin k dependent proteins which play critical roles in extracellular bone matrix mineralization. There is also credible evidence to support the effects of vitamin k2 on differentiation of other mesenchymal stem cells into osteoblast. The main objective of the present paper is to comprehensively outline the preclinical studies on the properties of vitamin K and its effects on the bone metabolism. The evidence could shed light on further clinical studies to improve osteogenesis in bone graft surgeries.
Topics: Bone and Bones; Calcification, Physiologic; Cell Differentiation; Osteoblasts; Osteogenesis; Vitamin K; Vitamin K 2
PubMed: 30050932
DOI: 10.1155/2018/4629383 -
Journal of Inherited Metabolic Disease Mar 2023
Topics: Humans; Vitamins; Vitamin A; Vitamin K; Vitamin B Complex
PubMed: 36550018
DOI: 10.1002/jimd.12585