Microbial Metabolite

Absorption, Distribution and Excretion
This study investigated the metabolic pathway of dihydroxyacetone (DHA) through in vitro absorption experiments. In these studies, the permeation and absorption of DHA in human skin over 24 or 72 hours were determined using a flow-through diffusion cell. …For DHA, permeation studies revealed that approximately 22% of the administered dose remained in the skin (stratum corneum and active tissue) after 24 hours, forming a drug reservoir. Only a very small amount of DHA permeated into the skin is absorbed systemically. Metabolism/Metabolites Some bacteria utilize glycerol dehydrogenase to convert glycerol into dihydroxyacetone (DHA). DHA is subsequently converted to dihydroxyacetone phosphate (DHA-P) via ATP or phosphoenolpyruvate (PEP)-dependent DHA kinases. Listeria innocua contains two potential PEP-dependent DHA kinases. One of these is encoded by three of the eleven genes constituting the glycerol (gol) operon. This operon also contains golD (lin0362), which encodes a novel DHA-to-NAD+-dependent glycerol dehydrogenase. Subsequent DHA metabolism requires phosphorylation via PEP: glucose phosphotransferase system component enzymes I, HPr, and EIIA(DHA)-2 (Lin0369). P-EIIA(DHA)-2 transfers its phosphate group to DhaL-2, which phosphorylates DHA bound to DhaK-2. The generated Dha-P is likely metabolized primarily via the pentose phosphate pathway, as two genes in the gol operon encode proteins similar to transketolases and transaldolases. Furthermore, purified Lin0363 and Lin0364 possess ribose-5-phosphate isomerase (RipB) and triose phosphate isomerase activities, respectively. The latter converts a portion of DHA-P to glyceraldehyde-3-phosphate, which, along with DHA-P, is metabolized via gluconeogenesis to fructose-6-phosphate. Transketolase, along with another glyceraldehyde-3-phosphate molecule, is an intermediate in the fructose-6-phosphate conversion pathway. The gol operon is preceded by the golR gene, which is transcribed in the opposite direction and encodes a DeoR-type repressor protein. Inactivation of the golR gene results in constitutive expression of the entire gol operon (including the last gene), but this expression can be repressed by glucose. The last gene encodes a PedB-like lactobacillus immune protein. Compared to wild-type strains or PedB-like deletion mutants, the golR mutant exhibits increased levels of this protein synthesis, leading to slightly enhanced immunity to lactobacillus PA-1.

Interactions
...Intake of dihydroxyacetone and pyruvate (DHP) increases glucose uptake in normal male muscles. To verify whether these three-carbon compounds can improve glycemic control in diabetic patients, we evaluated the effects of DHP on plasma glucose concentration, turnover, reuse, and tolerability in seven female patients with non-insulin-dependent diabetes mellitus. Subjects consumed a 1500-calorie diet (55% carbohydrates, 30% fat, 15% protein) three times daily, with 13% of calories randomly derived from either DHP (1/1) or Polycose (placebo; PL) for seven days. On day 8, continuous infusion of [6-(3)H]-glucose and U-(14)C-glucose began at 5:00 AM, followed by a 3-hour glucose tolerance test (75 g glucose) at 9:00 AM. Two weeks later, subjects repeated the study with a different dietary regimen. Fasting blood glucose levels decreased by 14% in the DHP group (DHP = 8.0 ± 0.9 mmol/L; PL = 9.3 ± 1.0 mmol/L, p < 0.05), which explained the decrease in blood glucose levels after oral administration (DHP = 13.1 ± 0.8 mmol/L, PL = 14.7 ± 0.8 mmol/L, p < 0.05). The 6-(3)H-glucose turnover rate (1.50 ± 0.19 mg/kg-L/min in the DHP group and 1.77 ± 0.21 mg/kg-L/min in the PL group, p < 0.05) and glucose recycling rate (the difference between the 6-(3)H-glucose and U-(14)C-glucose turnover rates) both decreased with increasing DHP (0.25 ± 0.07 mg/kg-L/min in the DHP group and 0.54 ± 0.10 mg/kg-L/min in the PL group, p < 0.05). Fasting blood glucose, post-oral blood glucose, plasma insulin, glucagon, and C-peptide levels were not affected by DHP. A mixture of dihydroxyacetone and pyruvate. Dihydroxyacetone (DHA) effectively antagonized the lethal effects of cyanide in mice and rabbits, especially when used in combination with sodium thiosulfate. Oral administration of DHA (2 and 4 g/kg) 10 minutes before intraperitoneal injection of cyanide in mice increased the LD50 of cyanide from 5.7 mg/kg to 12 and 17.6 mg/kg, respectively. Oral administration of DHA 10–15 minutes before cyanide injection was the most effective way to prevent cyanide-induced death. Pre-oral administration of DHA (4 g/kg) followed by administration of sodium thiosulfate (1 g/kg) increased the LD50 of cyanide by 9.9 times. Furthermore, intravenous administration of DHA 5 minutes after subcutaneous injection of cyanide in rabbits increased the LD50 of cyanide from 6 mg/kg to over 11 mg/kg; while intravenous administration of sodium thiosulfate (1 g/kg) 5 minutes later only increased the LD50 to 8.5 mg/kg. DHA also prevented convulsions following cyanide poisoning. In mice, dihydroxyacetone (DHA) effectively antagonized potassium cyanide (CN) poisoning, especially when used in combination with another CN antidote, sodium thiosulfate. DHA alone or in combination with sodium thiosulfate also prevented cyanide-induced seizures. Intraperitoneal injection of DHA (2 g/kg) 2 minutes after subcutaneous CN injection or 10 minutes before CN injection increased the LD50 of CN (8.7 mg/kg) by 2.1-fold and 3.0-fold, respectively. Treatment with DHA and thiosulfate after CN injection increased the LD50 by 2.4-fold. Pretreatment with DHA and thiosulfate (1 g/kg) increased the LD50 of CN to 83 mg/kg. Administration of α-ketoglutarate (2.0 g/kg) instead of pyruvate 2 minutes after CN injection increased the LD50 of CN by 1.6-fold. Cytochrome oxidase activity in the brain, heart, and liver was also measured after in vivo CN treatment (with or without DHA). Pretreatment with DHA can prevent CN from inhibiting cytochrome oxidase activity, while post-CN treatment with DHA can accelerate the recovery of cytochrome oxidase activity, especially in brain and heart homogenates…

[1]. Novel Process for 1,3-Dihydroxyacetone Production from Glycerol. 1. Technological Feasibility Study and Process Design. Ind. Eng. Chem. Res. 2012, 51, 9, 3715–3721.

[2]. Optimization of 1,3-dihydroxyacetone production from crude glycerol by immobilized Gluconobacter oxydans MTCC 904. Bioresour Technol. 2016 Sep;216:1058-65.

Dihydroxyacetone is a ketotriose composed of acetone molecules with hydroxyl groups linked at positions 1 and 3. It is the simplest member of the ketosaccharides and the parent compound of glycerol compounds. Dihydroxyacetone can be used as a metabolite, antifungal agent, human metabolite, Saccharomyces cerevisiae metabolite, Escherichia coli metabolite, and mouse metabolite. It is a ketotriose and a primary α-hydroxy ketone. Dihydroxyacetone is a metabolite found or produced in Escherichia coli (K12 strain, MG1655 strain). The presence of dihydroxyacetone has also been reported in Arabidopsis thaliana, humans, and other organisms with relevant data. Dihydroxyacetone is a metabolite found or produced in Saccharomyces cerevisiae. It is a ketotriose compound. Adding 2,3-diphosphoglycerate to blood preservation solutions can better maintain 2,3-diphosphoglycerate levels during storage. It is readily phosphorylated to dihydroxyacetone phosphate by 3-kinases in erythrocytes. When used in combination with naphthoquinone compounds, it can act as a sunscreen.

---

Mechanism of Action
...The toxicity of dihydroxyacetone appears to be due to its intracellular conversion into aldehydes (presumably methylglyoxal), as glyoxalase mutants are sensitive to dihydroxyacetone. Based on the information that the gldA gene is located in the operon of the ptsA homolog and the talC gene encoding fructose-6-phosphate aldolase, this study proposes that the primary function of gldA is to clear dihydroxyacetone by converting the toxic substance into glycerol.

---

Therapeutic Use
The aim of this study was to evaluate the properties of a novel dihydroxyacetone (DHA) formulation in the treatment of vitiligo on exposed areas. ...Ten patients with vitiligo on their face and/or hands received treatment with a newly marketed, commercially available self-tanning cream containing 5% DHA. The DHA was applied every other day. After two weeks of treatment, eight of the ten patients showed very satisfactory cosmetic results in terms of characteristic pigmentation. The novel DHA formulation is a practical and widely accepted treatment method.
/EXPL THER/ Dihydroxyacetone (DHA) is a tricarbon sugar and a browning component found in commercially available tanning products without tanning. …This study tested the in vitro antifungal activity of DHA against dermatophytes, particularly dermatophytes and Candida species. Antifungal activity was determined using the broth microdilution method, following the Clinical and Laboratory Standards Institute (CLSI) guidelines for yeasts and filamentous fungi. The obtained data showed that its fungicidal activity ranged from 1.6 to 50 mg/mL. DHA exhibits antifungal properties at concentrations comparable to those found in tanning lotions, thus appearing to be a promising therapeutic agent for dermatophytes. Therefore, due to its ability to penetrate the stratum corneum, it is a potential low-toxicity antifungal agent for topical application. In a seven-month clinical trial conducted in spring, summer, and autumn, 30 UVA/B/Soret photosensitivity patients were sequentially treated with topical dihydroxyacetone (DHA), with naphthoquinone applied only before bedtime. Excellent photosensitivity was achieved, with no treatment failures or patient loss to follow-up. Eighteen of the 30 patients repeatedly extended their tolerance to photosensitivity over the seven months, able to tolerate 6 to 8 hours of midday sun exposure without sunburn under various occupational and leisure conditions…
/Experimental Treatment/…This study investigated the protective effect of topical dihydroxyacetone (DHA) against sun-induced skin cancer in light-colored, hairless hr/hr C3H/Tif mice. Three groups of mice received UV irradiation four times per week at a dose equivalent to four times the standard erythema dose (SED). One group received DHA twice per week (5% or 20%), while the other group received no application. Similarly, the other three groups of mice, after receiving DHA treatment, were then subjected to high-dose UV irradiation (8 times the standard erythema dose) to simulate skin burns. Two groups of mice (control group) received no irradiation but no treatment, or received only 20% DHA treatment. Skin pigmentation caused by UV-induced melanin production was easily distinguished from DHA-induced skin browning and measured using a non-invasive, semi-quantitative method. Topical application of 20% DHA reduced pigmentation induced by 4 times the standard erythema dose (SED) by 63%, but only reduced it by 28% in mice irradiated by 8 times the SED. Furthermore, topical application of 20% DHA significantly delayed the time to the appearance of the first ≥1 mm tumor (P=0.0012) and the third tumor (P=2 x 10⁻⁶) in mice irradiated with 4 SEDs. However, 20% DHA did not delay tumor development in mice irradiated with 8 SEDs. Application of 5% DHA had no effect on pigmentation or photocarcinogenicity.
/Experimental Treatment/…Intake of dihydroxyacetone and pyruvate (DHP) increased glucose uptake in normal male muscle. To verify whether these three-carbon compounds could improve glycemic control in diabetic patients, we evaluated the effects of DHP on plasma glucose concentration, turnover, reuse, and tolerability in seven female patients with non-insulin-dependent diabetes mellitus. Subjects consumed a 1500-calorie diet (55% carbohydrates, 30% fat, 15% protein) three times daily for seven consecutive days, with 13% of the calories randomly provided in the form of DHP (1/1) or polydextrose (placebo; PL). On day 8, continuous infusion of [6-(3)H]-glucose and [U-(14)C]-glucose began at 5:00 AM, followed by a 3-hour glucose tolerance test (75 g glucose) at 9:00 AM. Two weeks later, the study was repeated with a different dietary regimen. DHP reduced fasting blood glucose levels by 14% (DHP = 8.0 + or - 0.9 mmol/L; PL = 9.3 + or - 1.0 mmol/L, p < 0.05), which explains the reduction in blood glucose levels after oral administration (DHP = 13.1 + or - 0.8 mmol/L, PL = 14.7 + or - 0.8 mmol/L, p < 0.05). [6-(3)H]-glucose turnover (1.50 ± 0.19 mg/kg-L/min in the DHP group and 1.77 ± 0.21 mg/kg-L/min in the PL group, p < 0.05) and glucose recycling rate (the difference between [6-(3)H]-glucose and [U-(14)C]-glucose turnover) both decreased with increasing DHP (0.25 ± 0.07 mg/kg-L/min in the DHP group and 0.54 ± 0.10 mg/kg-L/min in the PL group, p < 0.05). Fasting blood glucose, post-oral blood glucose, plasma insulin, glucagon, and C-peptide levels were not affected by DHP. /A mixture of dihydroxyacetone and pyruvate/.

C3H6O3

90.08

90.031

96-26-4

26776-70-5

670

White to off-white solid

1.3±0.1 g/cm3

213.7±15.0 °C at 760 mmHg

75-80 °C

97.3±16.9 °C

0.0±0.9 mmHg at 25°C

1.455

-0.78

2

3

2

6

44

0

O=C(CO)CO

RXKJFZQQPQGTFL-UHFFFAOYSA-N

InChI=1S/C3H6O3/c4-1-3(6)2-5/h4-5H,1-2H2

1,3-dihydroxypropan-2-one

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO :~100 mg/mL (~1110.12 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (27.75 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (27.75 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (27.75 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

 (Please use freshly prepared in vivo formulations for optimal results.)