Microbial Metabolite

Absorption, Distribution and Excretion
The present study investigated the fate of dihydroxyacetone (DHA) in an in vitro absorption study. In these studies, human ... skin penetration and absorption were determined over 24 or 72 hr in flow-through diffusion cells. ... For DHA, penetration studies found approximately 22% of the applied dose remaining in the skin (in both the stratum corneum and viable tissue) as a reservoir after 24 hr. Little of the DHA that penetrates into skin is actually available to become systemically absorbed.

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Metabolism / Metabolites
Several bacteria use glycerol dehydrogenase to transform glycerol into dihydroxyacetone (DHA). DHA is subsequently converted into DHA phosphate (DHA-P) by an ATP- or phosphoenolpyruvate (PEP)-dependent DHA kinase. Listeria innocua possesses two potential PEP-dependent Dha kinases. One is encoded by 3 of the 11 genes forming the glycerol (gol) operon. This operon also contains golD (lin0362), which codes for a new type of DHA-forming NAD(+)-dependent glycerol dehydrogenase. The subsequent metabolism of DHA requires its phosphorylation via the PEP:sugar phosphotransferase system components enzyme I, HPr, and EIIA(DHA)-2 (Lin0369). P-EIIA(DHA)-2 transfers its phosphoryl group to DhaL-2, which phosphorylates DHA bound to DhaK-2. The resulting Dha-P is probably metabolized mainly via the pentose phosphate pathway, because two genes of the gol operon encode proteins resembling transketolases and transaldolases. In addition, purified Lin0363 and Lin0364 exhibit ribose-5-P isomerase (RipB) and triosephosphate isomerase activities, respectively. The latter enzyme converts part of the DHA-P into glyceraldehyde-3-P, which, together with DHA-P, is metabolized via gluconeogenesis to form fructose-6-P. Together with another glyceraldehyde-3-P molecule, the transketolase transforms fructose-6-P into intermediates of the pentose phosphate pathway. The gol operon is preceded by golR, transcribed in the opposite orientation and encoding a DeoR-type repressor. Its inactivation causes the constitutive but glucose-repressible expression of the entire gol operon, including the last gene, encoding a pediocin immunity-like (PedB-like) protein. Its elevated level of synthesis in the golR mutant causes slightly increased immunity against pediocin PA-1 compared to the wild-type strain or a pedB-like deletion mutant.

Interactions
... Consumption of dihydroxyacetone and pyruvate (DHP) increases muscle extraction of glucose in normal men. To test the hypothesis that these three-carbon compounds would improve glycemic control in diabetes the effect of DHP on plasma glucose concentration, turnover, recycling, and tolerance in 7 women with noninsulin-dependent diabetes /was evaluated/. The subjects consumed a 1,500-calorie diet (55% carbohydrate, 30% fat, 15% protein), randomly containing 13% of the calories as DHP (1/1) or Polycose (placebo; PL), as a drink three times daily for 7 days. On the 8th day, primed continuous infusions of [6-(3)H]-glucose and U-(14)C-glucose were begun at 05.00 hr, and at 09.00 hr a 3-hr glucose tolerance test (75 g glucola) was performed. Two weeks later the subjects repeated the study with the other diet. The fasting plasma glucose level decreased by 14% with DHP (DHP = 8.0 + or - 0.9 mmol/L; PL = 9.3 + or - 1.0 mmol/L, p less than 0.05) which accounted for lower postoral glucose glycemia (DHP = 13.1 + or - 0.8 mmol/L, PL = 14.7 + or - 0.8 mmol/L, p< 0.05). 6-(3)H-glucose turnover (DHP = 1.50 + or - 0.19 mg/kg-L/min, PL = 1.77 + or - 0.21 mmg/kg-L/min, p less than 0.05) and glucose recycling, the difference in 6-(3)H-glucose and U-(14)C-glucose turnover rates, decreased with DHP (DHP = 0.25 + or - 0.07 mg/kg-L/min, PL = 0.54 + or - 0.10 mg/kg-L/min, p< 0.05). Fasting and postoral glucose, plasma insulin, glucagon, and C peptide levels were unaffected by DHP. /Mixture of dihydroxyacetone and pyruvate/.
Dihydroxyacetone (DHA) effectively antagonized the lethal effect of cyanide in mice and rabbits, particularly if administered in combination with thiosulfate. Oral DHA (2 and 4 g/kg) given to mice 10 min before injection (ip) of cyanide increased the LD50 values of cyanide from 5.7 mg/kg to 12 and 17.6 mg/kg, respectively. DHA prevented cyanide-induced lethality most effectively, if given orally 10-15 min before injection of cyanide. A combination of pretreatment with oral DHA (4 g/kg) and post-treatment with sodium thiosulfate (1 g/kg) increased the LD50 of cyanide by a factor of 9.9. Furthermore, DHA given intravenously to rabbits 5 min after subcutaneous injection of cyanide increased the LD50 of cyanide from 6 mg/kg to more than 11 mg/kg, while thiosulfate (1 g/kg) given intravenously 5 min after cyanide injection increased the LD50 of cyanide only to 8.5 mg/kg. DHA also prevented the convulsions that occurred after cyanide intoxication.
Potassium cyanide (CN) intoxication in mice was found to be effectively antagonized by dihydroxyacetone (DHA), particularly if administered in combination with another CN antidote, sodium thiosulfate. Cyanide-induced convulsions were also prevented by DHA treatment, either alone or in combination with thiosulfate. Injection (ip) of DHA (2 g/kg) 2 min after or 10 min before CN (sc) increased LD50 values of CN (8.7 mg/kg) by factors of 2.1 and 3.0, respectively. Treatment with a combination of DHA and thiosulfate after CN increased the LD50 by a factor of 2.4. Pretreatment with a combination of DHA and thiosulfate (1 g/kg) increased the LD50 of CN to 83 mg/kg. Administration of alpha-ketoglutarate (2.0 g/kg), but not pyruvate, 2 min after CN increased the LD50 of CN by a factor of 1.6. Brain, heart and liver cytochrome oxidase activities were also measured following in vivo CN treatment with and without DHA. Pretreatment with DHA prevented the inhibition of cytochrome oxidase activity by CN and treatment with DHA after CN accelerated 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 consisting of acetone bearing hydroxy substituents at positions 1 and 3. The simplest member of the class of ketoses and the parent of the class of glycerones. It has a role as a metabolite, an antifungal agent, a human metabolite, a Saccharomyces cerevisiae metabolite, an Escherichia coli metabolite and a mouse metabolite. It is a ketotriose and a primary alpha-hydroxy ketone.
Dihydroxyacetone is a metabolite found in or produced by Escherichia coli (strain K12, MG1655).
Dihydroxyacetone has been reported in Arabidopsis thaliana, Homo sapiens, and other organisms with data available.
Dihydroxyacetone is a metabolite found in or produced by Saccharomyces cerevisiae.
A ketotriose compound. Its addition to blood preservation solutions results in better maintenance of 2,3-diphosphoglycerate levels during storage. It is readily phosphorylated to dihydroxyacetone phosphate by triokinase in erythrocytes. In combination with naphthoquinones it acts as a sunscreening agent.

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Mechanism of Action
...The toxicity of dihydroxyacetone appears to be due to its intracellular conversion to an aldehyde compound, presumably methylglyoxal, since the glyoxalase mutant becomes sensitive to dihydroxyacetone. Based on information that gldA is preceded in an operon by the ptsA homolog and talC gene encoding fructose 6-phosphate aldolase, this study proposes that the primary role of gldA is to remove toxic dihydroxyacetone by converting it into glycerol.

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Therapeutic Uses
/The objective of this study was/ to evaluate the properties of dihydroxyacetone (DHA) in a new formulation for the treatment of vitiligo on exposed areas. ... Ten patients suffering from vitiligo affecting the face and/or hands /were treated/ with a newly introduced, commercially available self-bronzing cream containing DHA 5%. DHA was applied every second day. The characteristic pigmentation showed very satisfactory cosmetic results in 8 out of 10 patients after 2 weeks of treatment. The new DHA formulation is a practical and well-accepted treatment modality.
/EXPL THER/ Dihydroxyacetone (DHA), a three-carbon sugar, is the browning ingredient in commercial sunless tanning formulations. ... In this work, the in vitro antifungal activity of dihydroxyacetone was tested against causative agents of dermatomycosis, more specifically against dermatophytes and Candida spp. The antifungal activity was determined by the broth microdilution method according to the Clinical and Laboratory Standards Institute guidelines for yeasts and filamentous fungi. The data obtained show that the fungicidal activity varied from 1.6 to 50 mg/mL. DHA seems to be a promising substance for the treatment of dermatomycosis because it has antifungal properties at the same concentration used in artificial suntan lotions. Therefore, it is a potential low-toxicity antifungal agent that may be used topically because of its penetration into the corneal layers of the skin.
During seven months of a clinical trial in spring, summer, and fall, 30 UVA/B/Soret band-photosensitive patients used sequential topical applications of dihydroxyacetone (DHA) followed by naphthoquinone only at bedtime and received excellent photoprotection without a single therapeutic failure or loss of any patient to follow-up. Eighteen of the 30 patients extended the limits of their photoprotection repeatedly over a seven-month period to tolerate without sunburns six to eight hrs of midday sunlight under all kinds of occupational and recreational environmental conditions ...
/EXPTL THER/ ... the protection with topical application of dihydroxyacetone (DHA) against solar UV-induced skin carcinogenesis in lightly pigmented hairless hr/hr C3H/Tif mice /was investigated/. ... Three groups of mice were UV-exposed four times a wk to a dose-equivalent of four times the standard erythema dose (SED), without or with application of 5 or 20% DHA only twice a week. Similarly, three groups of mice were treated with DHA and irradiated with a high UV dose (8 standard erythema dose), simulating a skin burn. Two groups (controls) were not irradiated, but either left untreated or treated with 20% DHA alone. The UV-induced skin pigmentation by melanogenesis could easily be distinguished from DHA-induced browning and was measured by a non-invasive, semi-quantitative method. Application of 20% DHA reduced by 63% the pigmentation produced by 4 standard erythema dose, however, only by 28% the pigmentation produced by 8 standard erythema dose. Furthermore, topical application of 20% DHA significantly delayed the time to appearance of the first tumor >or=1mm (P=0.0012) and the time to appearance of the third tumor (P=2 x 10(-6)) in mice irradiated with 4 standard erythema dose. However, 20% DHA did not delay tumor development in mice irradiated with 8 standard erythema dose. Application of 5% DHA did not influence pigmentation or photocarcinogenesis.
/EXPTL THER/ ... Consumption of dihydroxyacetone and pyruvate (DHP) increases muscle extraction of glucose in normal men. To test the hypothesis that these three-carbon compounds would improve glycemic control in diabetes the effect of DHP on plasma glucose concentration, turnover, recycling, and tolerance in 7 women with noninsulin-dependent diabetes /was evaluated/. The subjects consumed a 1,500-calorie diet (55% carbohydrate, 30% fat, 15% protein), randomly containing 13% of the calories as DHP (1/1) or Polycose (placebo; PL), as a drink three times daily for 7 days. On the 8th day, primed continuous infusions of [6-(3)H]-glucose and [U-(14)C]-glucose were begun at 05.00 hr, and at 09.00 hr a 3-hr glucose tolerance test (75 g glucola) was performed. Two weeks later the subjects repeated the study with the other diet. The fasting plasma glucose level decreased by 14% with DHP (DHP = 8.0 + or - 0.9 mmol/L; PL = 9.3 + or - 1.0 mmol/L, p less than 0.05) which accounted for lower postoral glucose glycemia (DHP = 13.1 + or - 0.8 mmol/L, PL = 14.7 + or - 0.8 mmol/L, p less than 0.05). [6-(3)H]-glucose turnover (DHP = 1.50 + or - 0.19 mg/kg-L/min, PL = 1.77 + or - 0.21 mmg/kg-L/min, p less than 0.05) and glucose recycling, the difference in [6-(3)H]-glucose and [U-(14)C]-glucose turnover rates, decreased with DHP (DHP = 0.25 + or - 0.07 mg/kg-L/min, PL = 0.54 + or - 0.10 mg/kg-L/min, p less than 0.05). Fasting and postoral glucose, plasma insulin, glucagon, and C peptide levels were unaffected by DHP. /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.

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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.

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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.

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