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The Journal of Biological Chemistry 2021Understanding the pathways involved in chlorophyll breakdown provides a molecular map to the color changes observed in plant life on a global scale each fall....
Understanding the pathways involved in chlorophyll breakdown provides a molecular map to the color changes observed in plant life on a global scale each fall. Surprisingly, little is known about the fate of phytol, chlorophyll's 20-carbon branched-chain tail, during this process. A recent study from Gutbrod et al. provides evidence using physiological, genetic, and exquisitely sensitive analytical approaches that phytenal is an intermediate in plant phytol catabolism. These insights and techniques open the door to further investigation of this complicated metabolic system, with implications for plant health and agriculture.
Topics: Arabidopsis; Chlorophyll; Phytol; Plant Leaves
PubMed: 34022219
DOI: 10.1016/j.jbc.2021.100802 -
Plant Molecular Biology Mar 2023Tocopherols are potent membrane-bound antioxidant molecules that are paramount for plant physiology and also important for human health. In the past years, chlorophyll...
Tocopherols are potent membrane-bound antioxidant molecules that are paramount for plant physiology and also important for human health. In the past years, chlorophyll catabolism was identified as the primary source of phytyl diphosphate for tocopherol synthesis by the action of two enzymes, PHYTOL KINASE (VTE5) and PHYTHYL PHOSPHATE KINASE (VTE6) that are able to recycle the chlorophyll-derived phytol. While VTE5 and VTE6 were proven essential for tocopherol metabolism in tomato fruits, it remains unknown whether they are rate-limiting steps in this pathway. To address this question, transgenic tomato plants expressing AtVTE5 and AtVTE6 in a fruit-specific manner were generated. Although ripe transgenic fruits exhibited higher amounts of tocopherol, phytol recycling revealed a more intimate association with chlorophyll than with tocopherol content. Interestingly, protein-protein interactions assays showed that VTE5 and VTE6 are complexed, channeling free phytol and phytyl-P, thus mitigating their cytotoxic nature. Moreover, the analysis of tocopherol accumulation dynamics in roots, a chlorophyll-devoid organ, revealed VTE5-dependent tocopherol accumulation, hinting at the occurrence of shoot-to-root phytol trafficking. Collectively, these results demonstrate that phytol recycling is essential for tocopherol biosynthesis, even in chlorophyll-devoid organs, yet it is not the rate-limiting step for this pathway under normal growth conditions.
Topics: Humans; Tocopherols; Fruit; Solanum lycopersicum; Phytol; Chlorophyll; Plants, Genetically Modified
PubMed: 36587296
DOI: 10.1007/s11103-022-01331-3 -
Animal : An International Journal of... Mar 2021The phytol moiety in chlorophyll molecules acts as an agonist of peroxisome proliferator-activated receptor-α in monogastric animals. The current study aimed to clarify...
The phytol moiety in chlorophyll molecules acts as an agonist of peroxisome proliferator-activated receptor-α in monogastric animals. The current study aimed to clarify the effects of dietary supplementation with phytol on the plasma concentrations of formate and amino acids related to one-carbon (1C) donors and its effects on lipid metabolism in sheep. Four mature sheep were fed with a mixed ration (metabolizable energy, 10.7 MJ/kg DM; CP, 150 g/kg DM) comprising barley, rice bran, soybean meal, and oat hay at 1.5 times maintenance metabolizable energy for three consecutive 14-day experimental periods. The first and third periods served as controls without phytol supplementation, while in the second period, phytol was added to the mixed ration at 12 g/kg of dietary DM per day. In each period, feces, urine, and jugular blood samples were collected. Dry matter intake in relation to metabolic BW was slightly lower (P < 0.01) in the first period than the second and third periods but did not differ between the latter two periods. Dry matter digestibility was slightly reduced (P = 0.05) by the phytol treatment. Nitrogen (N) intake and retention showed similar trends to DM intake, but urinary N was unchanged among the periods. Plasma cholesterol and phospholipid concentrations decreased during the phytol treatment period, while triglyceride concentration increased (P < 0.05). In the phytol treatment period, the plasma concentrations of serine and glycine (1C donors) increased, but the glutamate level decreased (P < 0.01). Plasma concentrations of formate and methionine increased (P < 0.01) from the first control period to the phytol supplementation period, but homocysteine and cysteine (intermediate and by-product of the methionine cycle) levels were unchanged among the treatment periods. In conclusion, dietary phytol affects lipid metabolism as well as amino acid metabolism and 1C donors in sheep. These effects may be associated with the activity of phytol as an agonist of the nuclear receptors, although this needs further investigation.
Topics: Amino Acids; Animal Feed; Animals; Diet; Dietary Supplements; Digestion; Formates; Lipids; Phytol; Plasma; Rumen; Sheep
PubMed: 33610515
DOI: 10.1016/j.animal.2021.100174 -
Inhalation Toxicology Jan 2021The use of vaping pens for inhalation of cannabinoid derived products is rising and has become a popular alternative to smoking combustible products. For efficient...
The use of vaping pens for inhalation of cannabinoid derived products is rising and has become a popular alternative to smoking combustible products. For efficient product delivery, additives are sometimes added and vaping pens often may include compounds like Phytol or Propylene Glycol as thinning agents. This study aimed at comparing Phytol and Propylene Glycol with respect to potential toxicity and safe use in vaping products. Male and female Sprague Dawley rats were exposed to 5 mg/L of Phytol or Propylene Glycol for up to 6 hours over up to 14 days and monitored for clinical signs and changes in body weight. Gross necropsy and histopathology of respiratory tissue was performed to assess potential adverse effects. Phytol exposed animals expressed severe clinical signs, body weight loss and mortality after one or two exposure days, leading to termination of all dose groups for this compound. Lung weights were increased and respiratory tissue was severely affected, demonstrating dose-responsive tissue degeneration, necrosis, edema, hemorrhage and inflammation. Propylene Glycol exposed animals did not show any adverse reactions after 14 days of high dose exposure. For Phytol, a low observed adverse effect level (LOAEL) was determined at ≤109.0/10.9 mg/kg/day presented/deposited dose and therefore its use as excipient in vaping product is not recommend; a safe exposure range was not established for Phytol. Propylene Glycol, in contrast, is considered safe with a no observed adverse effect level (NOAEL) at 1151.7/115.2 mg/kg/day presented/deposited dose in rats.
Topics: Animals; Female; Inhalation Exposure; Lung Injury; Male; Phytol; Propylene Glycol; Rats; Rats, Sprague-Dawley
PubMed: 33441006
DOI: 10.1080/08958378.2020.1867260 -
Pediatric Research May 1986Infantile Refsum's disease is characterized by high levels of phytanic acid and the absence of normal hepatic peroxisomes. We investigated the in vivo influence of...
Infantile Refsum's disease is characterized by high levels of phytanic acid and the absence of normal hepatic peroxisomes. We investigated the in vivo influence of phytol, a precursor of phytanic acid, on peroxisomes by both biochemical and morphological methods. Enhanced supply of phytol in the diet of adult mice causes proliferation of hepatic peroxisomes. The peroxisomal beta-oxidizing capacity as well as exchanges of acyl moieties between peroxisomes and mitochondria are raised around 5- and 2-fold, respectively. In parallel a 1.5-fold increase of total catalase and mitochondrial butyryl-CoA dehydrogenase activities occurs, whereas peroxisomal urate oxidase and glycolate oxidase remain normally active. Serum triglyceride levels are decreased after 3 wk of phytol feeding; serum cholesterol levels remain unaffected. Phytol feeding also induces peroxisome proliferation in duodenal epithelium, in myocardium and in skin sebaceous glands, but not in kidney.
Topics: Animals; Catalase; Cholesterol; Diet; Diterpenes; Female; Humans; Infant; Liver; Male; Mice; Microbodies; Phytol; Refsum Disease; Triglycerides
PubMed: 2423950
DOI: 10.1203/00006450-198605000-00007 -
Food and Chemical Toxicology : An... Nov 2018Phytol (PYT) is a diterpene member of the long-chain unsaturated acyclic alcohols. PYT and some of its derivatives, including phytanic acid (PA), exert a wide range of...
Phytol (PYT) is a diterpene member of the long-chain unsaturated acyclic alcohols. PYT and some of its derivatives, including phytanic acid (PA), exert a wide range of biological effects. PYT is a valuable essential oil (EO) used as a fragrance and a potential candidate for a broad range of applications in the pharmaceutical and biotechnological industry. There is ample evidence that PA may play a crucial role in the development of pathophysiological states. Focusing on PYT and some of its most relevant derivatives, here we present a systematic review of reported biological activities, along with their underlying mechanism of action. Recent investigations with PYT demonstrated anxiolytic, metabolism-modulating, cytotoxic, antioxidant, autophagy- and apoptosis-inducing, antinociceptive, anti-inflammatory, immune-modulating, and antimicrobial effects. PPARs- and NF-κB-mediated activities are also discussed as mechanisms responsible for some of the bioactivities of PYT. The overall goal of this review is to discuss recent findings pertaining to PYT biological activities and its possible applications.
Topics: Adjuvants, Immunologic; Analgesics; Animals; Anti-Anxiety Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Anticonvulsants; Antineoplastic Agents; Antioxidants; Apoptosis; Autophagy; Biotechnology; Drug Industry; Drug Screening Assays, Antitumor; Humans; Microbial Sensitivity Tests; Oils, Volatile; Peroxisome Proliferator-Activated Receptors; Phytol; Plant Oils
PubMed: 30130593
DOI: 10.1016/j.fct.2018.08.032 -
Experimental Parasitology May 2021The quest for the development of a novel antimalarial drug informed the decision to subject phytol to in vivo trials following a demonstration of therapeutic potential...
The quest for the development of a novel antimalarial drug informed the decision to subject phytol to in vivo trials following a demonstration of therapeutic potential against chloroquine sensitive strain of Plasmodium falciparum under in vitro condition. On this basis, the in vivo anti-Plasmodium berghei activity of phytol including the ameliorative effects of the compound on P. berghei-associated anaemia and organ damage were investigated. Mice were infected with chloroquine-sensitive strain of P. berghei and were treated with phytol at a dose of 10 and 20 mg/kg body weight (BW) for four days. The levels of parasitemia, packed cell volume and redox sensitive biomarkers of liver, brain and spleen tissues were determined. Our result revealed that phytol significantly (p < 0.05) suppressed the multiplication of P. berghei in a dose-dependent manner. Additionally, the phytol significantly (p < 0.05) ameliorated the P. berghei-induced anaemia and brain damage. Data from the present study demonstrated that phytol has suppressive effect on P. berghei and could ameliorate some P. berghei-induced pathological changes.
Topics: Analysis of Variance; Anemia; Animals; Antimalarials; Brain; Chloroquine; Dose-Response Relationship, Drug; Female; Hematocrit; Liver; Malaria; Male; Mice; Oxidation-Reduction; Parasitemia; Phytol; Plasmodium berghei; Random Allocation; Spleen
PubMed: 33736972
DOI: 10.1016/j.exppara.2021.108097 -
Toxicologic Pathology Feb 2009Phytanic acid is a branched-chain, saturated fatty acid present in high concentrations in dairy products and ruminant fat. Some other dietary fats contain lower levels...
Phytanic acid is a branched-chain, saturated fatty acid present in high concentrations in dairy products and ruminant fat. Some other dietary fats contain lower levels of phytol, which is readily converted to phytanic acid after absorption. Phytanic acid is a peroxisome proliferator binding the nuclear transcription factor peroxisome proliferator-activated receptor alpha (PPARalpha) to induce expression of genes encoding enzymes of fatty acid oxidation in peroxisomes and mitochondria. Administration of dietary phytol (0.5% or 1%) to normal mice for twelve to eighteen days caused consistent PPARalpha-mediated responses, such as lower body weights, higher liver weights, peroxisome proliferation, increased catalase expression, and hepatocellular hypertrophy and hyperplasia. Female mice fed 0.5% phytol and male and female mice fed 1% phytol exhibited midzonal hepatocellular necrosis, periportal hepatocellular fatty vacuolation, and corresponding increases in liver levels of the phytol metabolites phytanic acid and pristanic acid. Hepatic expression of sterol carrier protein-x (SCP-x) was five- to twelve-fold lower in female mice than in male mice. These results suggest that phytol may cause selective midzonal hepatocellular necrosis in mice, an uncommon pattern of hepatotoxic injury, and that the greater susceptibility of female mice may reflect a lower capacity to oxidize phytanic acid because of their intrinsically lower hepatic expression of SCP-x.
Topics: Animals; Apoptosis; Body Weight; Carrier Proteins; Cell Death; Dose-Response Relationship, Drug; Fatty Acids; Female; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Necrosis; Organ Size; PPAR alpha; Peroxisomes; Phytanic Acid; Phytol; Reference Standards; Sex Factors; Time Factors
PubMed: 19188468
DOI: 10.1177/0192623308330789 -
Expert Opinion on Drug Delivery Apr 2013The development of vaccines is considered a key milestone in preventive medicine. There is no comparable cost-effective means for controlling or eradicating infectious... (Review)
Review
INTRODUCTION
The development of vaccines is considered a key milestone in preventive medicine. There is no comparable cost-effective means for controlling or eradicating infectious diseases. Yet, a persistent societal problem is the concern about vaccine's safety and long-term effects, and this caters to detractors of vaccination. Pathogen-derived antigen(s) as well as adjuvants/immunostimulants are essential for vaccine efficacy. Currently, adjuvant selection is largely empirical, but the mechanism underlying adjuvanticity is beginning to unravel. This should help develop more defined or targeted adjuvants.
AREAS COVERED
This review provides a brief account and analysis of the host immune parameters modulated by some commonly used as well as new adjuvants, including phytol-based diterpenoids. The major efforts are directed toward evaluating their relative safety and immunomodulatory efficiency, compared to known synthetic and natural adjuvants. Concerns for adverse pathological inflammation and autoimmunity are also addressed.
EXPERT OPINION
The phytol-based adjuvants hold great promise for improving vaccine efficacy, as they cause little or no persistent inflammation, but are highly effective in stimulating a multifaceted immune response, characterized by proficient recruitment of immune cells, generation of antibody and immunological memory, and activation of both Th1 and Th2 responses. Future focus will be on developing cocktail adjuvants to activate the complement system, mobilize follicular T helper cells as well as NKT and γδ T cells and activate cross-presenting dendritic cells to stimulate CD8(+) effector T cells.
Topics: Adjuvants, Immunologic; Chemistry, Pharmaceutical; Diterpenes; Humans; Phytol; T-Lymphocytes, Helper-Inducer; Vaccination; Vaccines
PubMed: 23293963
DOI: 10.1517/17425247.2013.757591 -
Molecular Plant-microbe Interactions :... Mar 2021Root-knot nematodes (RKNs; spp.) parasitize the roots or stems of a wide range of plant species, resulting in severe damage to the parasitized plant. The phytohormone...
Root-knot nematodes (RKNs; spp.) parasitize the roots or stems of a wide range of plant species, resulting in severe damage to the parasitized plant. The phytohormone ethylene (ET) plays an important role in signal transduction pathways leading to resistance against RKNs. However, little is currently known about the induction mechanisms of ET-dependent RKN resistance. Inoculation of roots with RKNs decreased chlorophyll contents in aerial parts of the plant. We observed accumulation of phytol, a constituent of chlorophyll and a precursor of tocopherols, in RKN-parasitized roots. Application of sclareol, a diterpene that has been shown to induce ET-dependent RKN resistance, to the roots of plants increased phytol contents in roots accompanied by a decrease in chlorophyll in aerial parts. Exogenously applied phytol inhibited RKN penetration of roots without exhibiting nematicidal activity. This phytol-induced inhibition of RKN penetration was attenuated in the ET-insensitive mutant . Exogenously applied phytol enhanced the production of α-tocopherol and expression of , a gene involved in tocopherol production, in roots. α-Tocopherol exerted induction of RKN resistance similar to that of phytol and showed increased accumulation in roots inoculated with RKNs. Furthermore, the mutant displayed no inhibition of RKN penetration in response to phytol. These results suggest that exogenously applied phytol induces EIN2-dependent RKN resistance, possibly via tocopherol production.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.
Topics: Animals; Arabidopsis; Disease Resistance; Ethylenes; Gene Expression Regulation, Plant; Phytol; Plant Diseases; Plant Roots; Signal Transduction; Tylenchoidea
PubMed: 33166202
DOI: 10.1094/MPMI-07-20-0186-R