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Journal of Cosmetic Dermatology Jan 2023As the desire and popularity of a tanned appearance continues, the social effects of UV-free tanning are becoming more important. Dihydroxyacetone (DHA) has seen... (Review)
Review
As the desire and popularity of a tanned appearance continues, the social effects of UV-free tanning are becoming more important. Dihydroxyacetone (DHA) has seen extensive use as the main tanning agent in sunless tanners. The DHA-induced tan is a result of brown melanoidins formed by a non-enzymatic Maillard reaction between DHA and amino acid species found in the stratum corneum. DHA, thereby, provides a safer route to a tanned appearance compared with exposure to ultraviolet radiation. However, DHA is a highly reactive molecule, posing a multitude of challenges for potential product formulations. With their increased use, the safety considerations of topically applied DHA tanners have been investigated. Many different vehicles have been used for topical delivery of DHA, and they are becoming increasingly multifunctional. This review provides a holistic overview of dihydroxyacetone sunless tanning products.
Topics: Humans; Dihydroxyacetone; Ultraviolet Rays; Epidermis; Amino Acids; Drug Compounding
PubMed: 35384270
DOI: 10.1111/jocd.14968 -
The Journal of Biological Chemistry May 2017Glucose metabolism promotes insulin secretion in β-cells via metabolic coupling factors that are incompletely defined. Moreover, chronically elevated glucose causes...
Glucose metabolism promotes insulin secretion in β-cells via metabolic coupling factors that are incompletely defined. Moreover, chronically elevated glucose causes β-cell dysfunction, but little is known about how cells handle excess fuels to avoid toxicity. Here we sought to determine which among the candidate pathways and coupling factors best correlates with glucose-stimulated insulin secretion (GSIS), define the fate of glucose in the β-cell, and identify pathways possibly involved in excess-fuel detoxification. We exposed isolated rat islets for 1 h to increasing glucose concentrations and measured various pathways and metabolites. Glucose oxidation, oxygen consumption, and ATP production correlated well with GSIS and saturated at 16 mm glucose. However, glucose utilization, glycerol release, triglyceride and glycogen contents, free fatty acid (FFA) content and release, and cholesterol and cholesterol esters increased linearly up to 25 mm glucose. Besides being oxidized, glucose was mainly metabolized via glycerol production and release and lipid synthesis (particularly FFA, triglycerides, and cholesterol), whereas glycogen production was comparatively low. Using targeted metabolomics in INS-1(832/13) cells, we found that several metabolites correlated well with GSIS, in particular some Krebs cycle intermediates, malonyl-CoA, and lower ADP levels. Glucose dose-dependently increased the dihydroxyacetone phosphate/glycerol 3-phosphate ratio in INS-1(832/13) cells, indicating a more oxidized state of NAD in the cytosol upon glucose stimulation. Overall, the data support a role for accelerated oxidative mitochondrial metabolism, anaplerosis, and malonyl-CoA/lipid signaling in β-cell metabolic signaling and suggest that a decrease in ADP levels is important in GSIS. The results also suggest that excess-fuel detoxification pathways in β-cells possibly comprise glycerol and FFA formation and release extracellularly and the diversion of glucose carbons to triglycerides and cholesterol esters.
Topics: Adenosine Triphosphate; Animals; Cell Line; Cholesterol Esters; Dihydroxyacetone Phosphate; Dose-Response Relationship, Drug; Fatty Acids; Glucose; Glycerophosphates; Glycogen; Insulin-Secreting Cells; Male; Malonyl Coenzyme A; Rats; Rats, Wistar; Signal Transduction; Triglycerides
PubMed: 28280244
DOI: 10.1074/jbc.M116.763060 -
Cellular Physiology and Biochemistry :... 2019Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD) worldwide, and the importance of tubular injury has been highlighted in recent years.... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND/AIMS
Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD) worldwide, and the importance of tubular injury has been highlighted in recent years. However, the underlying mechanisms and effective therapeutic targets are still unclear. In this study, we investigated mtDNA, mitochondrial dynamics, function and metabolic pathways to determine if mitochondrial damage plays a critical role in the development of tubular injury in DKD patients.
METHODS
A cross-sectional study was carried out among healthy controls (HCs, n = 65), diabetes patients without kidney disease (DCs, n = 48) and DKD patients (n = 60). Serum, peripheral blood mononuclear cells (PBMCs) and kidney biopsy specimens were obtained from participants. Metabolomics was employed to investigate cellular metabolism.
RESULTS
DKD patients had decreased mtDNA copy numbers and increased mtDNA damage compared to DCs. Mitochondrial fragmentation was specifically presented in tubules, but not in podocytes of DKD patients. The accumulation of damaged mtDNA and fragmented mitochondria resulted in increased reactive oxygen species (ROS) generation, activation of apoptosis and loss of mitochondrial membrane potential (ΔΨm) in tubules and PBMCs. Furthermore, glycolysis and tricarboxylic acid (TCA) cycle was perturbed, and increased dihydroxyacetone phosphate (DHAP) and decreased succinyl-CoA synthetase (SCS) respectively in these two metabolic pathways were identified as potential biomarkers for tubular injury in DKD.
CONCLUSION
Our study indicates that mitochondrial damage could be the hallmark of tubular injury in DKD patients, and this would provide a novel and attractive therapeutic target to improve this disease.
Topics: Cross-Sectional Studies; DNA, Mitochondrial; Diabetic Nephropathies; Female; Humans; Kidney Failure, Chronic; Kidney Tubules; Male; Membrane Potential, Mitochondrial; Metabolomics; Middle Aged; Mitochondria
PubMed: 30816665
DOI: 10.33594/000000011 -
Photodiagnosis and Photodynamic Therapy Mar 2023Patients with erythropoietic protoporphyria (EPP) are hypersensitive to long wave ultraviolet (UVA) radiation and visible light and they experience severe skin pain by... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Patients with erythropoietic protoporphyria (EPP) are hypersensitive to long wave ultraviolet (UVA) radiation and visible light and they experience severe skin pain by light exposure. The patients have very limited treatment options. Sunless skin tanning with dihydroxyacetone (DHA) is now being investigated as a possible treatment modality of skin photosensitivity in EPP.
METHODS
We simulated the theoretical light protection factor provided by DHA application. In addition, we present 19 cases with EPP who were treated at our department with DHA weekly during spring and summer from 2018 to 2021 inclusive.
RESULTS
The protection factor against UVA and visible light was estimated to approximately two. Out of the 19 patients with EPP who were treated with DHA in 2018, 11 patients experienced a sustained good effect and continued to use the treatment on a weekly basis in the spring and summer of 2019, 2020, and 2021.
CONCLUSION AND PERSPECTIVES
Both the theoretical estimates and the uncontrolled study suggest that sunless tanning with DHA reduces photosensitivity in patients with EPP. Our hypothesis is that skin treated with DHA can tolerate twice the daylight dose compared to untreated skin before onset of skin symptoms. To validate this conclusion, we plan a randomized clinical trial to determine the effect of DHA application to reduce photosensitivity in patients with EPP under controlled clinical conditions. The study protocol for this trial is presented in the paper.
Topics: Humans; Protoporphyria, Erythropoietic; Dihydroxyacetone; Photochemotherapy; Photosensitizing Agents; Light; Photosensitivity Disorders
PubMed: 36690194
DOI: 10.1016/j.pdpdt.2023.103302 -
Frontiers in Veterinary Science 2024Brucellosis is a worldwide extended zoonosis caused by pathogens of the genus . While most , , and biovars grow slowly in complex media, they multiply intensely in...
Brucellosis is a worldwide extended zoonosis caused by pathogens of the genus . While most , , and biovars grow slowly in complex media, they multiply intensely in livestock genitals and placenta indicating high metabolic capacities. Mutant analyses and in infection models emphasize that erythritol (abundant in placenta and genitals) is a preferred substrate of brucellae, and suggest hexoses, pentoses, and gluconeogenic substrates use in host cells. While sugar and erythritol catabolic pathways are known, growth on 3-4 carbon substrates persists in Fbp- and GlpX-deleted mutants, the canonical gluconeogenic fructose 1,6-bisphosphate (F1,6bP) bisphosphatases. Exploiting the prototrophic and fast-growing properties of biovar 5, we show that gluconeogenesis requires fructose-bisphosphate aldolase (Fba); the existence of a novel broad substrate bisphosphatase (Bbp) active on sedoheptulose 1,7-bisphosphate (S1,7bP), F1,6bP, and other phosphorylated substrates; that Fbp unexpectedly acts on S1,7bP and F1,6bP; and that, while active in and , GlpX is disabled in biovar 5. Thus, two Fba-dependent reactions (dihydroxyacetone-phosphate + glyceraldehyde 3-phosphate ⇌ F1,6bP; and dihydroxyacetone-phosphate + erythrose 4-phosphate ⇌ S1,7bP) can, respectively, yield fructose 6-phosphate and sedoheptulose 7-phosphate for classical gluconeogenesis and the Pentose Phosphate Shunt (PPS), the latter reaction opening a new gluconeogenic route. Since erythritol generates the PPS-intermediate erythrose 4-phosphate, and the Fba/Fbp-Bbp route predicts sedoheptulose 7-phosphate generation from erythrose 4-phosphate, we re-examined the erythritol connections with PPS. Growth on erythritol required transaldolase or the Fba/Fbp-Bbp pathway, strongly suggesting that Fba/Fbp-Bbp works as a PPS entry for both erythritol and gluconeogenic substrates in . We propose that, by increasing erythritol channeling into PPS through these peculiar routes, brucellae proliferate in livestock genitals and placenta in the high numbers that cause abortion and infertility, and make brucellosis highly contagious. These findings could be the basis for developing attenuated brucellosis vaccines safer in pregnant animals.
PubMed: 38601913
DOI: 10.3389/fvets.2024.1328293 -
Bioresources and Bioprocessing Jul 2022Catalytic valorization of raw glycerol derived from biodiesel into high-value chemicals has attracted great attention. Here, we report chemoenzymatic cascade reactions...
Catalytic valorization of raw glycerol derived from biodiesel into high-value chemicals has attracted great attention. Here, we report chemoenzymatic cascade reactions that convert glycerol to lactic acid and glycolic acid. In the enzymatic step, a coenzyme recycling system was developed to convert glycerol into 1,3-dihydroxyacetone (DHA) with a yield of 92.3% in potassium phosphate buffer (300 mM, pH 7.1) containing 100 mM glycerol, 2 mM NAD, 242 U/mL glycerol dehydrogenase-GldA and NADH oxidase-SpNox at 30 °C. Subsequently, NaOH or NaClO catalyzes the formation of lactic acid and glycolic acid from DHA. The high yield of lactic acid (72.3%) and glycolic acid (78.2%) verify the benefit of the chemoenzymatic approaches.
PubMed: 38647569
DOI: 10.1186/s40643-022-00561-z -
Microbiology Spectrum Apr 2024All organisms utilize -adenosyl-l-methionine (SAM) as a key co-substrate for the methylation of biological molecules, the synthesis of polyamines, and radical SAM...
UNLABELLED
All organisms utilize -adenosyl-l-methionine (SAM) as a key co-substrate for the methylation of biological molecules, the synthesis of polyamines, and radical SAM reactions. When these processes occur, 5'-deoxy-nucleosides are formed as byproducts such as -adenosyl-l-homocysteine, 5'-methylthioadenosine (MTA), and 5'-deoxyadenosine (5dAdo). A prevalent pathway found in bacteria for the metabolism of MTA and 5dAdo is the dihydroxyacetone phosphate (DHAP) shunt, which converts these compounds into dihydroxyacetone phosphate and 2-methylthioacetaldehyde or acetaldehyde, respectively. Previous work in other organisms has shown that the DHAP shunt can enable methionine synthesis from MTA or serve as an MTA and 5dAdo detoxification pathway. Rather, the DHAP shunt in ATCC 25922, when introduced into K-12, enables the use of 5dAdo and MTA as a carbon source for growth. When MTA is the substrate, the sulfur component is not significantly recycled back to methionine but rather accumulates as 2-methylthioethanol, which is slowly oxidized non-enzymatically under aerobic conditions. The DHAP shunt in ATCC 25922 is active under oxic and anoxic conditions. Growth using 5-deoxy-d-ribose was observed during aerobic respiration and anaerobic respiration with Trimethylamine N-oxide (TMAO), but not during fermentation or respiration with nitrate. This suggests the DHAP shunt may only be relevant for extraintestinal pathogenic lineages with the DHAP shunt that inhabit oxic or TMAO-rich extraintestinal environments. This reveals a heretofore overlooked role of the DHAP shunt in carbon and energy metabolism from ubiquitous SAM utilization byproducts and suggests a similar role may occur in other pathogenic and non-pathogenic bacteria with the DHAP shunt.
IMPORTANCE
The acquisition and utilization of organic compounds that serve as growth substrates are essential for to grow and multiply. Ubiquitous enzymatic reactions involving S-adenosyl-l-methionine as a co-substrate by all organisms result in the formation of the 5'-deoxy-nucleoside byproducts, 5'-methylthioadenosine and 5'-deoxyadenosine. All possess a conserved nucleosidase that cleaves these 5'-deoxy-nucleosides into 5-deoxy-pentose sugars for adenine salvage. The DHAP shunt pathway is found in some extraintestinal pathogenic , but its function in possessing it has remained unknown. This study reveals that the DHAP shunt enables the utilization of 5'-deoxy-nucleosides and 5-deoxy-pentose sugars as growth substrates in strains with the pathway during aerobic respiration and anaerobic respiration with TMAO, but not fermentative growth. This provides an insight into the diversity of sugar compounds accessible by with the DHAP shunt and suggests that the DHAP shunt is primarily relevant in oxic or TMAO-rich extraintestinal environments.
Topics: S-Adenosylmethionine; Escherichia coli; Dihydroxyacetone Phosphate; Methionine; Bacteria; Pentoses; Carbon; Sugars; Deoxyadenosines; Methylamines; Thionucleosides
PubMed: 38441472
DOI: 10.1128/spectrum.03086-23 -
Biomedicine & Pharmacotherapy =... Feb 2023Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are characterized by skin photosensitivity caused by accumulation of protoporphyrin IX. We aimed to... (Review)
Review
Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are characterized by skin photosensitivity caused by accumulation of protoporphyrin IX. We aimed to review the clinical evidence of efficacy and safety of skin photosensitivity treatments in individuals with EPP or XLP. We systematically searched MEDLINE, Embase, the Cochrane Library, and ClinicalTrials.gov. A total of 40 studies with data on 18 treatment modalities were included. Comprehensive treatment safety data were obtained from the European Medicines Agency and the United States Food and Drug Administration. The studies used different outcome measures to evaluate the sensitivity without a generally accepted method to assess treatment effect on skin photosensitivity. Of the included studies, 13 were controlled trials. Gathered, the trials showed moderate positive effect of inorganic sunscreen application and subcutaneous implant of afamelanotide and no effect of organic sunscreen application, or oral treatment with beta-carotene, cysteine, N-acetylcysteine, vitamin C, or warfarin. Studies without control groups suggested treatment effect of foundation cream, dihydroxyacetone/lawsone cream, narrow-band ultraviolet B phototherapy, erythrocyte transfusion, extracorporeal erythrocyte photodynamic therapy, or oral treatment with zinc sulphate, terfenadine, cimetidine, or canthaxanthin, but the real effect is uncertain. Assessment of treatment effect on photosensitivity in patients with EPP or XLP carries a high risk of bias since experienced photosensitivity varies with both weather conditions, exposure pattern, and pigmentation. Controlled trials of promising treatment options are important although challenging in this small patient population.
Topics: United States; Humans; Protoporphyria, Erythropoietic; Sunscreening Agents; Photosensitivity Disorders; Genetic Diseases, X-Linked; Protoporphyrins
PubMed: 36525819
DOI: 10.1016/j.biopha.2022.114132 -
Nature Communications Oct 2022Many biomass intermediates are polyols and selectively oxidizing only a primary or secondary alcohol group is beneficial for the valorization of these intermediates. For...
Many biomass intermediates are polyols and selectively oxidizing only a primary or secondary alcohol group is beneficial for the valorization of these intermediates. For example, production of 1,3-dihydroxyacetone, a highly valuable oxidation product of glycerol, requires selective secondary alcohol oxidation. However, selective secondary alcohol oxidation is challenging due to its steric disadvantage. This study demonstrates that NiOOH, which oxidizes alcohols via two dehydrogenation mechanisms, hydrogen atom transfer and hydride transfer, can convert glycerol to 1,3-dihydroxyacetone with high selectivity when the conditions are controlled to promote hydrogen atom transfer, favoring secondary alcohol oxidation. This rational production of 1,3-dihydroxyacetone achieved by selectively enabling one desired dehydrogenation pathway, without requiring alteration of catalyst composition, demonstrates how comprehensive mechanistic understanding can enable predictive control over selectivity.
Topics: Catalysis; Dihydroxyacetone; Ethanol; Glycerol; Hydrogen
PubMed: 36195626
DOI: 10.1038/s41467-022-33637-7 -
Aging and Disease May 2017Recent research shows that energy metabolism can strongly influence proteostasis and thereby affect onset of aging and related disease such as Parkinson's disease (PD).... (Review)
Review
On the Relationship between Energy Metabolism, Proteostasis, Aging and Parkinson's Disease: Possible Causative Role of Methylglyoxal and Alleviative Potential of Carnosine.
Recent research shows that energy metabolism can strongly influence proteostasis and thereby affect onset of aging and related disease such as Parkinson's disease (PD). Changes in glycolytic and proteolytic activities (influenced by diet and development) are suggested to synergistically create a self-reinforcing deleterious cycle via enhanced formation of triose phosphates (dihydroxyacetone-phosphate and glyceraldehyde-3-phosphate) and their decomposition product methylglyoxal (MG). It is proposed that triose phosphates and/or MG contribute to the development of PD and its attendant pathophysiological symptoms. MG can induce many of the macromolecular modifications (e.g. protein glycation) which characterise the aged-phenotype. MG can also react with dopamine to generate a salsolinol-like product, 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinaline (ADTIQ), which accumulates in the Parkinson's disease (PD) brain and whose effects on mitochondria, analogous to MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), closely resemble changes associated with PD. MG can directly damage the intracellular proteolytic apparatus and modify proteins into non-degradable (cross-linked) forms. It is suggested that increased endogenous MG formation may result from either, or both, enhanced glycolytic activity and decreased proteolytic activity and contribute to the macromolecular changes associated with PD. Carnosine, a naturally-occurring dipeptide, may ameliorate MG-induced effects due, in part, to its carbonyl-scavenging activity. The possibility that ingestion of highly glycated proteins could also contribute to age-related brain dysfunction is briefly discussed.
PubMed: 28580188
DOI: 10.14336/AD.2016.1030