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Nature Metabolism Sep 2020The mechanistic target of rapamycin complex 1 (mTORC1) kinase regulates cell growth by setting the balance between anabolic and catabolic processes. To be active, mTORC1...
The mechanistic target of rapamycin complex 1 (mTORC1) kinase regulates cell growth by setting the balance between anabolic and catabolic processes. To be active, mTORC1 requires the environmental presence of amino acids and glucose. While a mechanistic understanding of amino acid sensing by mTORC1 is emerging, how glucose activates mTORC1 remains mysterious. Here, we used metabolically engineered human cells lacking the canonical energy sensor AMP-activated protein kinase to identify glucose-derived metabolites required to activate mTORC1 independent of energetic stress. We show that mTORC1 senses a metabolite downstream of the aldolase and upstream of the GAPDH-catalysed steps of glycolysis and pinpoint dihydroxyacetone phosphate (DHAP) as the key molecule. In cells expressing a triose kinase, the synthesis of DHAP from DHA is sufficient to activate mTORC1 even in the absence of glucose. DHAP is a precursor for lipid synthesis, a process under the control of mTORC1, which provides a potential rationale for the sensing of DHAP by mTORC1.
Topics: AMP-Activated Protein Kinases; Dihydroxyacetone; Dihydroxyacetone Phosphate; Energy Metabolism; Fructose-Bisphosphate Aldolase; Glucose; Glycolysis; HEK293 Cells; Humans; Lipid Metabolism; Phosphotransferases (Alcohol Group Acceptor); TOR Serine-Threonine Kinases
PubMed: 32719541
DOI: 10.1038/s42255-020-0250-5 -
Journal of Drugs in Dermatology : JDD Apr 2018The sunless tanning industry has experienced rapid growth due to public education on the dangers of ultraviolet radiation on skin and improvements in products.... (Review)
Review
The sunless tanning industry has experienced rapid growth due to public education on the dangers of ultraviolet radiation on skin and improvements in products. Dihydroxyacetone (DHA) is a 3-carbon sugar allowed by the Food and Drug Administration (FDA) as a color additive in sunless tanning products. Bronzers, a product removed with soap and water, may also contain DHA. We aim to review the literature on DHA. DHA is intended for external application, not including the mucous membranes or in or around the eye area. DHA has been used in spray-tan booths and by airbrushing it onto consumers, although these are unapproved uses, as contact with the color additive is not restricted to the external part of the body. Consequently, the FDA recommends customers shield their eyes, lips, and mucous membranes, as well as refrain from ingestion or inhalation of DHA. Unlike sunscreens, products that protect against ultraviolet radiation and are regulated by the FDA as non-prescription drugs, sunless tanning products are regulated as cosmetics and cannot provide any protection from exposure to ultraviolet radiation. There are reports of non-cosmetic uses of DHA that are not FDA approved. With the wide-spread use of DHA, additional studies on its safety are warranted.
J Drugs Dermatol. 2018;17(4):387-391.
.Topics: Cosmetics; Dihydroxyacetone; Humans; Skin Pigmentation; Sunscreening Agents; Suntan; Ultraviolet Rays
PubMed: 29601614
DOI: No ID Found -
Molecules (Basel, Switzerland) Mar 20231,3-dihydroxyacetone (DHA) is an underrated bio-based synthon, with a broad range of reactivities. It is produced for the revalorization of glycerol, a major... (Review)
Review
1,3-dihydroxyacetone (DHA) is an underrated bio-based synthon, with a broad range of reactivities. It is produced for the revalorization of glycerol, a major side-product of the growing biodiesel industry. The overwhelming majority of DHA produced worldwide is intended for application as a self-tanning agent in cosmetic formulations. This review provides an overview of the discovery, physical and chemical properties of DHA, and of its industrial production routes from glycerol. Microbial fermentation is the only industrial-scaled route but advances in electrooxidation and aerobic oxidation are also reported. This review focuses on the plurality of reactivities of DHA to help chemists interested in bio-based building blocks see the potential of DHA for this application. The handling of DHA is delicate as it can undergo dimerization as well as isomerization reactions in aqueous solutions at room temperature. DHA can also be involved in further side-reactions, yielding original side-products, as well as compounds of interest. If this peculiar reactivity was harnessed, DHA could help address current sustainability challenges encountered in the synthesis of speciality polymers, ranging from biocompatible polymers to innovative polymers with cutting-edge properties and improved biodegradability.
Topics: Dihydroxyacetone; Glycerol; Fermentation; Oxidation-Reduction; Cosmetics
PubMed: 36985712
DOI: 10.3390/molecules28062724 -
Journal of the American Academy of... Dec 1992Dihydroxyacetone-containing sunless or self-tanning topical preparations are enjoying a resurgence of use in recent years. The chemistry of dihydroxyacetone, mechanism... (Review)
Review
Dihydroxyacetone-containing sunless or self-tanning topical preparations are enjoying a resurgence of use in recent years. The chemistry of dihydroxyacetone, mechanism of action, application, safety, indications, and available products are reviewed.
Topics: Coloring Agents; Cosmetics; Dermatologic Agents; Dihydroxyacetone; Humans; Ointments; Skin Pigmentation
PubMed: 1479107
DOI: 10.1016/0190-9622(92)70300-5 -
Environmental and Molecular Mutagenesis Mar 2021Dihydroxyacetone (DHA) is a three-carbon sugar that is the active ingredient in sunless tanning products and a by-product of electronic cigarette (e-cigarette)... (Review)
Review
Dihydroxyacetone (DHA) is a three-carbon sugar that is the active ingredient in sunless tanning products and a by-product of electronic cigarette (e-cigarette) combustion. Increased use of sunless tanning products and e-cigarettes has elevated exposures to DHA through inhalation and absorption. Studies have confirmed that DHA is rapidly absorbed into cells and can enter into metabolic pathways following phosphorylation to dihydroxyacetone phosphate (DHAP), a product of fructose metabolism. Recent reports have suggested metabolic imbalance and cellular stress results from DHA exposures. However, the impact of elevated exposure to DHA on human health is currently under-investigated. We propose that exogenous exposures to DHA increase DHAP levels in cells and mimic fructose exposures to produce oxidative stress, mitochondrial dysfunction, and gene and protein expression changes. Here, we review cell line and animal model exposures to fructose to highlight similarities in the effects produced by exogenous exposures to DHA. Given the long-term health consequences of fructose exposure, this review emphasizes the pressing need to further examine DHA exposures from sunless tanning products and e-cigarettes.
Topics: Dihydroxyacetone; Dihydroxyacetone Phosphate; Fructose; Humans; Metabolic Networks and Pathways; Mitochondria; Oxidative Stress; Phosphorylation
PubMed: 33496975
DOI: 10.1002/em.22425 -
Photodermatology, Photoimmunology &... Nov 2023Sunless tanning products have risen in popularity as the desire for a tanned appearance continues alongside growing concerns about the deleterious effects of ultraviolet... (Review)
Review
Sunless tanning products have risen in popularity as the desire for a tanned appearance continues alongside growing concerns about the deleterious effects of ultraviolet radiation exposure from the sun. Dihydroxyacetone (DHA) is a simple carbohydrate found nearly universally in sunless tanning products that serves to impart color to the skin. The Food and Drug Administration (FDA), which regulates sunless tanning products as cosmetics, allows DHA for external use while maintaining that its ingestion, inhalation, or contact with mucosal surfaces should be avoided. Given its widespread use and a paucity of reviews on its safety, we aim to review the literature on the topical properties and safety profile of DHA. Available data indicate that DHA possesses only minimal to no observable photoprotective properties. In vitro studies suggest that, while DHA concentrations much higher than those in sunless tanning products are needed to induce significant cytotoxicity, even low millimolar, nonlethal concentrations can alter the function of keratinocytes, tracheobronchial cells, and other cell types on a cellular and molecular level. Instances of irritant and allergic contact dermatitis triggered by DHA exposures have also been reported. While no other side effects in humans have been observed, additional studies on the safety and toxicity of DHA in humans are warranted, with a focus on concentrations and frequencies of DHA exposure typically encountered by consumers.
Topics: Humans; Dihydroxyacetone; Ultraviolet Rays; Sunbathing; Cosmetics; Skin Pigmentation
PubMed: 37697919
DOI: 10.1111/phpp.12913 -
The British Journal of Dermatology Jul 1960
Topics: Acetone; Dihydroxyacetone; Pigmentation
PubMed: 14425215
DOI: 10.1111/j.1365-2133.1960.tb13891.x -
Journal of Biotechnology Nov 2021In this work, several immobilization strategies for Gluconobacter oxydans NBRC 14819 (Gox) were tested in the bioconversion of crude glycerol to dihydroxyacetone (DHA)....
In this work, several immobilization strategies for Gluconobacter oxydans NBRC 14819 (Gox) were tested in the bioconversion of crude glycerol to dihydroxyacetone (DHA). Agar, agarose and polyacrylamide were evaluated as immobilization matrixes. Glutaraldehyde crosslinked versions of the agar and agarose preparations were also tested. Agar immobilized Gox proved to be the best heterogeneous biocatalyst in the bioconversion of crude glycerol reaching a quantitative production of 50 g/L glycerol into DHA solely in water. Immobilization allowed reutilization for at least eight cycles, reaching four times more DHA than the amount obtained by a single batch of free cells which cannot be reutilized. An increase in scale of 34 times had no impact on DHA productivity. The results obtained herein constitute a contribution to the microbiological production of DHA as they not only attain unprecedented productivities for the reaction with immobilized biocatalysts but also proved that it is feasible to do it in a clean background of solely water that alleviates the cost of downstream processing.
Topics: Biotransformation; Dihydroxyacetone; Gluconobacter oxydans; Glycerol
PubMed: 34454960
DOI: 10.1016/j.jbiotec.2021.08.011 -
Dihydroxyacetone suppresses mTOR nutrient signaling and induces mitochondrial stress in liver cells.PloS One 2022Dihydroxyacetone (DHA) is the active ingredient in sunless tanning products and a combustion product from e-juices in electronic cigarettes (e-cigarettes). DHA is...
Dihydroxyacetone (DHA) is the active ingredient in sunless tanning products and a combustion product from e-juices in electronic cigarettes (e-cigarettes). DHA is rapidly absorbed in cells and tissues and incorporated into several metabolic pathways through its conversion to dihydroxyacetone phosphate (DHAP). Previous studies have shown DHA induces cell cycle arrest, reactive oxygen species, and mitochondrial dysfunction, though the extent of these effects is highly cell-type specific. Here, we investigate DHA exposure effects in the metabolically active, HepG3 (C3A) cell line. Metabolic and mitochondrial changes were evaluated by characterizing the effects of DHA in metabolic pathways and nutrient-sensing mechanisms through mTOR-specific signaling. We also examined cytotoxicity and investigated the cell death mechanism induced by DHA exposure in HepG3 cells. Millimolar doses of DHA were cytotoxic and suppressed glycolysis and oxidative phosphorylation pathways. Nutrient sensing through mTOR was altered at both short and long time points. Increased mitochondrial reactive oxygen species (ROS) and mitochondrial-specific injury induced cell cycle arrest and cell death through a non-classical apoptotic mechanism. Despite its carbohydrate nature, millimolar doses of DHA are toxic to liver cells and may pose a significant health risk when higher concentrations are absorbed through e-cigarettes or spray tanning.
Topics: Dihydroxyacetone; Electronic Nicotine Delivery Systems; Reactive Oxygen Species; Mitochondria; Liver
PubMed: 36472985
DOI: 10.1371/journal.pone.0278516 -
Biotechnology Advances 2008Dihydroxyacetone is extensively used in cosmetic industry as an artificial suntan besides having clinical and biological applications. Thus, it is important to meet the... (Review)
Review
Dihydroxyacetone is extensively used in cosmetic industry as an artificial suntan besides having clinical and biological applications. Thus, it is important to meet the commercial demand of dihydroxyacetone at an economical and qualitative level. Microbial route of production is found to be more favorable for dihydroxyacetone as compared to chemical methods. This review gives detailed information about the microbial route of dihydroxyacetone production. Till date the microorganism which is most utilized for dihydroxyacetone production is Gluconobacter oxydans. Some limitations associated with dihydroxyacetone production by G. oxydans like substrate inhibition, product inhibition and oxygen limitation are discussed here. Various fermentation modes and culture conditions have been tried for their ability to overcome these limitations. It has been found that fed-batch mode of fermentation provides a better yield as compared to batch mode for dihydroxyacetone production. Two-stage repeated fed-batch mode of fermentation has been found to be the most optimized mode. Immobilization has also been recognized as a much better alternative for fermentation since it avoids the problem of substrate and product inhibition to a greater extent. Although these methods have increased the dihydroxyacetone production to a prominent level yet the production has not reached the level required to meet the commercial demand. One looks for future prospects of developing recombinant microbial method for dihydoxyacetone production.
Topics: Bacteria; Cell Membrane; Cytoplasm; Dihydroxyacetone; Fermentation; Glycerol; Humans
PubMed: 18387770
DOI: 10.1016/j.biotechadv.2008.02.001