Human Endogenous Metabolite

Metabolism / Metabolites
Free fructose is directly absorbed by the intestines. When ingested as sucrose, fructose is digested (broken down) and then absorbed as free fructose. Fructose absorption occurs on the mucosa via facilitated transport involving the GLUT5 and GLUT2 transporters. In the liver, fructose is phosphorylated by fructose kinase (Km = 0.5 mM). Fructose kinase first produces fructose-1-phosphate, which is then broken down by aldolase B to produce the triose sugar dihydroxyacetone phosphate (DHAP) and glyceraldehyde. DHAP is subsequently converted to glycerol-3-phosphate, which stimulates the production of triglycerides. Of the pure fructose ingested, nearly half (45%) is used by the body for energy within 3–6 hours. If fructose is ingested with glucose (which is usually the case in nature), up to 66% of the fructose is used for energy within the same timeframe. Approximately one-third (29%) to half (54%) of the fructose is converted into glucose. Less than 1% of the fructose appears to be directly converted into triglycerides.

Toxicity Summary
Fructose differs from other sugars in that it can lead to intracellular ATP depletion, decreased nucleotide turnover, and uric acid production. Uric acid production is due to the rapid phosphorylation of fructose in the liver (forming fructose-1-phosphate), resulting in a rapid decrease in free phosphate and ATP. This decrease in ATP stimulates adenosine monophosphate (AMP) deaminase, which deaminates AMP to IMP, which is then converted to uric acid (A15346). Uric acid is normally an antioxidant, but it acts as a pro-oxidant when there is a deficiency of ascorbic acid (vitamin C) in the plasma. Because many soft drinks and foods sweetened with high-fructose corn syrup lack vitamin C, the resulting uric acid can lead to a range of harmful effects, including gout, chronic inflammation, high blood pressure, fat accumulation, fatty liver, and obesity (A15346). Numerous studies have shown that elevated uric acid levels are associated with a variety of metabolic and cardiovascular diseases, including diabetes and coronary artery disease (A15346). Elevated serum uric acid levels have also been proven to be the most reliable predictor of hypertension and kidney disease (A15347) and fatty liver (A15348). Fructose-induced uric acid production also leads to mitochondrial oxidative stress, thereby stimulating fat accumulation, independent of excessive calorie intake (A15349). Multiple studies have shown that oxidative stress is one of the earliest phenomena to occur after vascular, renal, hepatic, and adipocyte exposure to uric acid (A15347). High fructose intake is also associated with more severe ATP depletion in the liver, which may impair the liver's "energy balance." Studies have shown that high-fructose beverages also lead to decreased circulating insulin and leptin levels, and increased ghrelin levels. Since leptin and insulin reduce appetite, while ghrelin increases appetite, some researchers suspect that high fructose intake may increase the likelihood of weight gain.

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Toxicity Data
Daily intake of more than 100 grams of pure fructose may result in a moderate but statistically significant weight gain of 0.44 kg per week. Daily intake of 100 grams or more of fructose also significantly increases fasting serum triglyceride levels.
LD50: 15000 mg/kg (intravenous injection, rabbit)

[1]. Novel hydroxyamides and amides containing D-glucopyranose or D-fructose units: Biological assays in MCF-7 and MDST8 cell lines. Bioorg Med Chem Lett. 2016 Feb 1;26(3):1039-1043.

β-D-fructose is a D-fructose that plays a metabolic role in mice. It is the enantiomer of β-L-fructose. β-D-fructose has been reported in Daphnia pulex, Ruellia patula, and Detarium microcarpum, with supporting data. Fructose, also known as fructose, is a simple monosaccharide found in many plants, usually covalently linked to glucose to form the disaccharide sucrose. Fructose, along with glucose and galactose, is one of the three most common dietary monosaccharides, which can be directly absorbed into the bloodstream during digestion. Fructose is naturally found in many fruits, vegetables, and honey, and is also commonly extracted from sugarcane, sugar beets, and corn. High-fructose corn syrup (HFCS), a mixture of glucose and fructose, is widely used as a sweetener in beverages and foods. Fructose is widely used in food and beverages primarily because of its low cost and relatively high sweetness. It is the sweetest of all natural carbohydrates, 1.73 times sweeter than sucrose. Fructose consumption in the United States has more than doubled in the past 30 years. American fructose intake climbed from 15 grams per day in the early 20th century to 55 grams per day in 1994. This increase was largely attributed to increased consumption of soft drinks. Fructose is a monosaccharide found in sweet fruits and honey, and is soluble in water, alcohol, or ether. It is used as a preservative and also in intravenous parenteral nutrition. See also: D-fructose (note moved here).

C6H12O6

180.16

180.063

53188-23-1

439709

White to off-white solid powder

1.6±0.1 g/cm3

551.7±50.0 °C at 760 mmHg

119 - 122 °C

301.5±26.6 °C

0.0±3.4 mmHg at 25°C

1.574

-1.63

5

6

2

12

162

4

OCC(=O)C(O)C(O)C(O)CO

RFSUNEUAIZKAJO-ARQDHWQXSA-N

InChI=1S/C6H12O6/c7-1-3-4(9)5(10)6(11,2-8)12-3/h3-5,7-11H,1-2H2/t3-,4-,5+,6-/m1/s1

(2R,3S,4S,5R)-2,5-bis(hydroxymethyl)oxolane-2,3,4-triol

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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