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Molecular Plant Jan 2017Phytyl-diphosphate, which provides phytyl moieties as a common substrate in both tocopherol and phylloquinone biosynthesis, derives from de novo isoprenoid biosynthesis...
Phytyl-diphosphate, which provides phytyl moieties as a common substrate in both tocopherol and phylloquinone biosynthesis, derives from de novo isoprenoid biosynthesis or a salvage pathway via phytol phosphorylation. However, very little is known about the role and origin of the phytyl moiety for phylloquinone biosynthesis. Since VTE6, a phytyl-phosphate kinase, is a key enzyme for phytol phosphorylation, we characterized Arabidopsis vte6 mutants to gain insight into the roles of phytyl moieties in phylloquinone biosynthesis and of phylloquinone in photosystem I (PSI) biogenesis. The VTE6 knockout mutants vte6-1 and vte6-2 lacked detectable phylloquinone, whereas the phylloquinone content in the VTE6 knockdown mutant vte6-3 was 90% lower than that in wild-type. In vte6 mutants, PSI function was impaired and accumulation of the PSI complex was defective. The PSI core subunits PsaA/B were efficiently synthesized and assembled into the PSI complex in vte6-3. However, the degradation rate of PSI subunits in the assembled PSI complex was more rapid in vte6-3 than in wild-type. In vte6-3, PSI was more susceptible to high-light damage than in wild-type. Our results provide the first genetic evidence that the phytol phosphorylation pathway is essential for phylloquinone biosynthesis, and that phylloquinone is required for PSI complex stability.
Topics: Arabidopsis; Arabidopsis Proteins; Gene Knockout Techniques; Light; Mutation; Phosphorylation; Phosphotransferases (Alcohol Group Acceptor); Photosystem I Protein Complex; Phytol; Protein Stability; Vitamin K 1
PubMed: 28007557
DOI: 10.1016/j.molp.2016.12.006 -
Biochemical and Biophysical Research... Nov 2005The peroxisome proliferator-activated receptor (PPAR) is one of the indispensable transcription factors for regulating lipid metabolism in various tissues. In our...
Phytol directly activates peroxisome proliferator-activated receptor alpha (PPARalpha) and regulates gene expression involved in lipid metabolism in PPARalpha-expressing HepG2 hepatocytes.
The peroxisome proliferator-activated receptor (PPAR) is one of the indispensable transcription factors for regulating lipid metabolism in various tissues. In our screening for natural compounds that activate PPAR using luciferase assays, a branched-carbon-chain alcohol (a component of chlorophylls), phytol, has been identified as a PPARalpha-specific activator. Phytol induced the increase in PPARalpha-dependent luciferase activity and the degree of in vitro binding of a coactivator, SRC-1, to GST-PPARalpha. Moreover, the addition of phytol upregulated the expression of PPARalpha-target genes at both mRNA and protein levels in PPARalpha-expressing HepG2 hepatocytes. These findings indicate that phytol is functional as a PPARalpha ligand and that it stimulates the expression of PPARalpha-target genes in intact cells. Because PPARalpha activation enhances circulating lipid clearance, phytol may be important in managing abnormalities in lipid metabolism.
Topics: Animals; Base Sequence; Clofibric Acid; Gene Expression Regulation; Haplorhini; Hepatocytes; Humans; Lipid Metabolism; Liver; Luciferases; PPAR alpha; Phytanic Acid; Phytol; Transcription Factors; Tumor Cells, Cultured; Up-Regulation
PubMed: 16202384
DOI: 10.1016/j.bbrc.2005.09.077 -
Japanese Journal of Cancer Research :... Apr 1999Phytol is a branched, long-chain aliphatic alcohol which has various biological effects. In this study, we examined phytol as a tumor promoter in a mouse skin... (Comparative Study)
Comparative Study
Phytol is a branched, long-chain aliphatic alcohol which has various biological effects. In this study, we examined phytol as a tumor promoter in a mouse skin initiation-promotion model, and compared its promotion activity with that of 12-O-tetradecanoyl phorbol-13-acetate (TPA). Female ICR mice, 7 weeks of age, were initiated with 100 microg of 7,12-dimethylbenz(a)anthracene, and were then topically promoted twice a week for 16 weeks with 100 mg of phytol or with 2.5 microg of TPA. In this model 95% of animals treated with phytol developed skin tumors within 16 weeks. The average number of lesions per mouse treated with phytol was significantly lower than that in mice treated with TPA, and this significant difference continued up to 16 weeks after the end of promotion treatment. Characterization of hyperplasia 48 h after topical application of agents showed that epidermal thickness and vertical thickness following topical application of phytol were significantly increased compared with vehicle controls, but were significantly smaller than in animals treated with TPA. Ornithine decarboxylase (ODC) activity following topical application of phytol was increased in a dose-dependent manner and showed a weak, delayed induction (which was maximal 11-12 h after treatment) as compared with the case of TPA. The specific binding of [3H]phorbol-12,13-dibutyrate (PDBU) by JB6 cells was not inhibited by phytol at concentrations up to 1 mM. These results indicate that phytol has a weak tumor promoter activity compared to TPA and is a non-TPA-type tumor promoter in this model of mouse skin carcinogenesis.
Topics: Animals; Carcinogens; Female; Hyperplasia; Mice; Mice, Inbred ICR; Ornithine Decarboxylase; Phytol; Radioligand Assay; Tetradecanoylphorbol Acetate; Toxicity Tests
PubMed: 10363574
DOI: 10.1111/j.1349-7006.1999.tb00758.x -
Natural Product Research 2014The cytotoxicity of the diterpene alcohol, phytol, was evaluated by using the MTT assay in vitro against seven tumour cells and one normal cell of human origin. The...
The cytotoxicity of the diterpene alcohol, phytol, was evaluated by using the MTT assay in vitro against seven tumour cells and one normal cell of human origin. The compound tested induced concentration-dependent cytotoxic response in all cell lines, demonstrating to be most and least effective against the breast adenocarcinoma MCF-7 and the prostate adenocarcinoma PC-3 cells, respectively (IC50 8.79 ± 0.41 μM and 77.85 ± 1.93 μM). The IC50 values towards the other five tumours (HeLa, HT-29, A-549, Hs294T and MDA-MB-231) ranged from 15.51 to 69.67 μM. However, mild toxicity was detected against the foetal lung fibroblast MRC-5 cells at the concentrations used (IC50 124.84 ± 1.59 μM). According to the experimental data obtained, this cost-effective natural product widely present in the biosphere may inspire the development of new drug-like substances with improved cytotoxic activity on breast cancer.
Topics: Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Drug Screening Assays, Antitumor; Female; HT29 Cells; HeLa Cells; Humans; In Vitro Techniques; Inhibitory Concentration 50; MCF-7 Cells; Male; Molecular Structure; Phytol
PubMed: 24896297
DOI: 10.1080/14786419.2014.921686 -
Scientific Reports Oct 2020Phytol and tocopherols and their fatty acid esters (PFAE and TFAE) are isoprenoid lipid components which can be found for instance in vegetables. Their behavior during...
Phytol and tocopherols and their fatty acid esters (PFAE and TFAE) are isoprenoid lipid components which can be found for instance in vegetables. Their behavior during maturation of fruits and vegetables could reveal valuable information on their biosynthetic formation and biological function. As pods of the genus Capsicum contain considerable amounts of both PFAE and TFAE, two cultivars (i.e. Capsicum annuum var. Forajido and Capsicum chinense var. Habanero) were grown in a greenhouse project. The date of flowering and fruit formation of each blossom was noted and fruits were harvested in four specific periods which corresponded with different stages of ripening, i.e. unripe, semi-ripe, ripe and overripe. Quantification by means of gas chromatography mass spectrometry and creation of development profiles strongly supported the suggestion that PFAE and TFAE were formed as storage molecules during fruit ripening and parallel degradation of chlorophyll. Additionally, compound-specific carbon isotope ratios (δC values (‰)) of originally in PFAE and chlorophyll bound phytol ultimately proved that PFAE, besides tocopherols, serve as sink for the cytotoxic phytol moiety released from chlorophyll degradation during fruit ripening. Furthermore, color measurements were successfully implemented to simplify the usually cumbersome separation of chili fruits into different ripening degrees.
Topics: Capsicum; Chlorophyll; Color; Fruit; Phytol; Plant Physiological Phenomena; Tocopherols
PubMed: 33057127
DOI: 10.1038/s41598-020-74308-1 -
Biotechnology and Bioengineering Feb 2006A ferriprotoporphyrin, hemin (Fe(3+)), modified with 3,7,11,15-tetramethyl-2-hexadecen-1-ol, phytol, was adsorbed in nano-spaces of about 4 nm in diameter in mesoporous...
A ferriprotoporphyrin, hemin (Fe(3+)), modified with 3,7,11,15-tetramethyl-2-hexadecen-1-ol, phytol, was adsorbed in nano-spaces of about 4 nm in diameter in mesoporous silica (FSM; folded-sheet mesoporous material) forming a phytol-modified hemin (Fe(3+))-FSM nano-conjugate. The properties and the structure of the conjugate were studied by UV-visible light absorption, IR absorption spectroscopy, and a nitrogen adsorption isotherm. Although the hemin without phytol could not be adsorbed to the mesoporous silica, modification with phytol imparted preferential adsorption properties. The conjugate was not only stable but also had a peroxidase-like activity in a 0.1% hydrogen peroxide solution, while free hemin in the solution was easily destroyed. The hemin (Fe(3+)) in the FSM was reduced to heme (Fe(2+)) by hydrazine. The phytol-modified heme (Fe(2+))-FSM conjugate formed an O(2)-heme complex with a superoxide type structure, resembling oxyhemoglobin or oxymyoglobin, which has not been previously observed for free heme in solution. The addition of carbon monoxide or nitrogen monoxide to the phytol-modified heme (Fe(2+))-FSM conjugate caused the formation of CO- or NO-heme complex in the nano-spaces of the FSM. These properties are attributed not only to the Fe-complex but also to the cooperative functions of the heme with mesoporous silica, resembling properties of a natural heme-protein conjugate; hemoglobin or peroxidase. These results are an elegant example of biomimetic nano-technology.
Topics: Adsorption; Biomimetic Materials; Carbon Monoxide; Heme; Hemeproteins; Hemin; Hydrogen Peroxide; Nanotechnology; Nitric Oxide; Nitrogen; Oxygen; Phytol; Porosity; Silicon Dioxide
PubMed: 16193518
DOI: 10.1002/bit.20734 -
Fitoterapia Sep 2000Two new compounds, cedrellin (1) and 2,6,10,15-phytatetraene-14-ol (2), together with five known compounds, 7 alpha-obacunyl acetate, 6-acetoxyobacunol acetate, 7...
Two new compounds, cedrellin (1) and 2,6,10,15-phytatetraene-14-ol (2), together with five known compounds, 7 alpha-obacunyl acetate, 6-acetoxyobacunol acetate, 7 alpha-acetoxydihydronomilin, 2,6,10-phytatriene-1,14,15-triol and phytol were isolated from leaves of Cedrela sinensis. Their structures were elucidated on the basis of combined one- and two-dimensional spectral techniques.
Topics: Drugs, Chinese Herbal; Flavonoids; Humans; Limonins; Phytol; Plants, Medicinal; Rosales; Terpenes
PubMed: 11449495
DOI: 10.1016/s0367-326x(00)00158-1 -
The Journal of Biological Chemistry Feb 2006Chlorophyll is the most abundant photosynthetic pigment in higher plants. During senescence, chlorophyll is hydrolyzed, resulting in the release of free phytol and...
Chlorophyll is the most abundant photosynthetic pigment in higher plants. During senescence, chlorophyll is hydrolyzed, resulting in the release of free phytol and chlorophyllide. Although the degradation of chlorophyllide has been studied in depth, the metabolic fate of phytol in plants is less clear. Here, we provide evidence that phytol can be incorporated into chlorophyll, tocopherol, and lipid esters by Arabidopsis seedlings. Phytol is phosphorylated to phytyl-phosphate and phytyl-diphosphate by two successive kinase activities associated with chloroplast envelope membranes of Arabidopsis. Although phytol kinase is CTP-dependent, the second kinase reaction, phytyl-phosphate kinase, shows broader specificity for CTP, GTP, UTP, and ATP. Therefore, in addition to de novo synthesis from geranylgeranyl-diphosphate, phosphorylation of free phytol represents an alternative route for phytyl-diphosphate production as the precursor for chloroplast prenyl lipid synthesis. Lipid esters are produced after feeding phytol to Arabidopsis seedlings, and they also accumulate in large amounts in leaves during senescence. The predominant phytyl ester that accumulates during senescence is hexadecatrienoic acid phytyl ester. Fatty acid phytyl ester synthesis by protein extracts of Arabidopsis is stimulated in the presence of phytol- and acyl-CoA esters. Thus, Arabidopsis contains a distinct enzymatic machinery for redirecting free phytol released from chlorophyll degradation into chloroplast lipid metabolism.
Topics: Arabidopsis; Chlorophyll; Chloroplasts; Esters; Lipid Metabolism; Metabolism; Phosphorylation; Phytol; Protein Kinases
PubMed: 16306049
DOI: 10.1074/jbc.M509222200 -
Archives of Biochemistry and Biophysics Dec 2017While prior studies focusing on male mice suggest a role for sterol carrier protein-2/sterol carrier protein-x (SCP-2/SCP-x; DKO) on hepatic phytol metabolism, its role...
While prior studies focusing on male mice suggest a role for sterol carrier protein-2/sterol carrier protein-x (SCP-2/SCP-x; DKO) on hepatic phytol metabolism, its role in females is unresolved. This issue was addressed using female and male wild-type (WT) and DKO mice fed a phytoestrogen-free diet without or with 0.5% phytol. GC/MS showed that hepatic: i) phytol was absent and its branched-chain fatty acid (BCFA) metabolites were barely detectable in WT control-fed mice; ii) accumulation of phytol as well as its peroxisomal metabolite BCFAs (phytanic acid » pristanic and 2,3-pristenic acids) was increased by dietary phytol in WT females, but only slightly in WT males; iii) accumulation of phytol and BCFA was further increased by DKO in phytol-fed females, but much more markedly in males. Livers of phytol-fed WT female mice as well as phytol-fed DKO female and male mice also accumulated increased proportion of saturated straight-chain fatty acids (LCFA) at the expense of unsaturated LCFA. Liver phytol accumulation was not due to increased SCP-2 binding/transport of phytol since SCP-2 bound phytanic acid, but not its precursor phytol. Thus, the loss of Scp-2/Scp-x contributed to a sex-dependent hepatic accumulation of dietary phytol and BCFA.
Topics: Administration, Oral; Animals; Carrier Proteins; Female; Gene Silencing; Lipid Metabolism; Liver; Male; Metabolic Clearance Rate; Mice; Mice, Inbred C57BL; Mice, Knockout; Phytanic Acid; Phytol; Sex Factors
PubMed: 29051070
DOI: 10.1016/j.abb.2017.10.011 -
Journal of Lipid Research Jun 2017Studies in vitro have suggested that both sterol carrier protein-2/sterol carrier protein-x () and liver fatty acid binding protein [ (L-FABP)] gene products facilitate...
Studies in vitro have suggested that both sterol carrier protein-2/sterol carrier protein-x () and liver fatty acid binding protein [ (L-FABP)] gene products facilitate hepatic uptake and metabolism of lipotoxic dietary phytol. However, interpretation of physiological function in mice singly gene ablated in the has been complicated by concomitant upregulation of FABP1. The work presented herein provides several novel insights: ) An 8-anilino-1-naphthalenesulfonic acid displacement assay showed that neither SCP-2 nor L-FABP bound phytol, but both had high affinity for its metabolite, phytanic acid; ) GC-MS studies with phytol-fed WT and gene ablated [triple KO (TKO)] mice showed that TKO exacerbated hepatic accumulation of phytol metabolites in vivo in females and less so in males. Concomitantly, dietary phytol increased hepatic levels of total long-chain fatty acids (LCFAs) in both male and female WT and TKO mice. Moreover, in both WT and TKO female mice, dietary phytol increased hepatic ratios of saturated/unsaturated and polyunsaturated/monounsaturated LCFAs, while decreasing the peroxidizability index. However, in male mice, dietary phytol selectively increased the saturated/unsaturated ratio only in TKO mice, while decreasing the peroxidizability index in both WT and TKO mice. These findings suggested that: ) SCP-2 and FABP1 both facilitated phytol metabolism after its conversion to phytanic acid; and ) SCP-2/SCP-x had a greater impact on hepatic phytol metabolism than FABP1.
Topics: Animals; Carrier Proteins; Endoplasmic Reticulum; Fatty Acid-Binding Proteins; Female; Gene Knockout Techniques; Liver; Male; Mice; Peroxisomes; Phytanic Acid; Phytol; Substrate Specificity
PubMed: 28411199
DOI: 10.1194/jlr.M075457