5-Hydroxymethyl-2-furoic acid

Enzymatic conversion reactions of 5-hydroxymethylfurfural (HMF) to bio-based 2,5-diformylfuran (DFF) and 2,5-furandicarboxylic acid (FDCA) with air: mechanisms, pathways and synthesis selectivity.[Pubmed:32308735]

Biotechnol Biofuels. 2020 Apr 10;13:66.

Background: 2,5-Furandicarboxylic acid (FDCA) is one of the top biomass-derived value-added chemicals. It can be produced from fructose and other C6 sugars via formation of 5-hydroxymethilfurfural (HMF) intermediate. Most of the chemical methods for FDCA production require harsh conditions, thus as an environmentally friendly alternative, an enzymatic conversion process can be applied. Results: Commercially available horseradish peroxidase (HRP) and lignin peroxidase (LPO), alcohol (AO) and galactose oxidase (GO), catalase (CAT) and laccase (LAC) were tested against HMF, 2,5-diformylfuran (DFF), 5-Hydroxymethyl-2-furoic acid (HMFA) and 5-formyl-2-furoic acid (FFA). Enzyme concentrations were determined based on the number of available active sites and reactions performed at atmospheric oxygen pressure. AO, GO, HRP and LPO were active against HMF, where LPO and HRP produced 0.6 and 0.7% of HMFA, and GO and AO produced 25.5 and 5.1% DFF, respectively. Most of the enzymes had only mild (3.2% yield or less) or no activity against DFF, HMFA and FFA, with only AO having a slightly higher activity against FFA with an FDCA yield of 11.6%. An effect of substrate concentration was measured only for AO, where 20 mM HMF resulted in 19.5% DFF and 5 mM HMF in 39.9% DFF, with a K m value of 14 mM. Some multi-enzyme reactions were also tested and the combination of AO and CAT proved most effective in converting over 97% HMF to DFF in 72 h. Conclusions: Our study aimed at understanding the mechanism of conversion of bio-based HMF to FDCA by different selected enzymes. By understanding the reaction pathway, as well as substrate specificity and the effect of substrate concentration, we would be able to better optimize this process and obtain the best product yields in the future.

Parameters affecting the exposure to furfuryl alcohol from coffee.[Pubmed:29842908]

Food Chem Toxicol. 2018 Aug;118:473-479.

Recently, furfuryl alcohol (FFA) was labelled a human potential carcinogen (group 2B) by the International Agency for Research on Cancer. Its alimentary exposure is mostly from coffee since in any other foods the concentrations are significantly lower. The various storage conditions of roasted coffee, the different brewing techniques applied and the bioaccessibility after ingestion are potential parameters that might alter the exposure to FFA from coffee. An 8 weeks stability study at varying temperatures showed that FFA is stable in the ground coffee matrix. Moreover, different brewing techniques extracted different amounts of FFA and affected its final concentration. The evaluation of the relative exposure to four furans (FFA, 5-hydroxymethyl-furaldehyde, 2-furoic acid, and 5-Hydroxymethyl-2-furoic acid) revealed that FFA amounts were at least 2-fold the amounts of other studied furans in the same brew. A 22-fold variation in the concentration of the four furans in brews prepared using different coffee grounds and brewing techniques could be observed. 90% of the four furans were extracted by the first 25-30% fraction of the filter brew. A significant decrease of FFA is observed after stressing with simulated gastric fluid. However, this decrease could not be reproduced when mimicking a regular coffee ingestion situation.

Metabolic profiles from two different breakfast meals characterized by (1)H NMR-based metabolomics.[Pubmed:28450006]

Food Chem. 2017 Sep 15;231:267-274.

It is challenging to measure dietary exposure with techniques that are both accurate and applicable to free-living individuals. We performed a cross-over intervention, with 24 healthy individuals, to capture the acute metabolic response of a cereal breakfast (CB) and an egg and ham breakfast (EHB). Fasting and postprandial urine samples were analyzed using (1)H nuclear magnetic resonance (NMR) spectroscopy and multivariate data analysis. Metabolic profiles were distinguished in relation to ingestion of either CB or EHB. Phosphocreatine/creatine and citrate were identified at higher concentrations after consumption of EHB. Beverage consumption (i.e., tea or coffee) could clearly be seen in the data. 2-furoylglycine and 5-Hydroxymethyl-2-furoic acid - potential biomarkers for coffee consumption were identified at higher concentrations in coffee drinkers. Thus (1)H NMR urine metabolomics is applicable in the characterization of acute metabolic fingerprints from meal consumption and in the identification of metabolites that may serve as potential biomarkers.

Tolerance of the nanocellulose-producing bacterium Gluconacetobacter xylinus to lignocellulose-derived acids and aldehydes.[Pubmed:25186182]

J Agric Food Chem. 2014 Oct 8;62(40):9792-9.

Lignocellulosic biomass serves as a potential alternative feedstock for production of bacterial nanocellulose (BNC), a high-value-added product of bacteria such as Gluconacetobacter xylinus. The tolerance of G. xylinus to lignocellulose-derived inhibitors (formic acid, acetic acid, levulinic acid, furfural, and 5-hydroxymethylfurfural) was investigated. Whereas 100 mM formic acid completely suppressed the metabolism of G. xylinus, 250 mM of either acetic acid or levulinic acid still allowed glucose metabolism and BNC production to occur. Complete suppression of glucose utilization and BNC production was observed after inclusion of 20 and 30 mM furfural and 5-hydroxymethylfurfural, respectively. The bacterium oxidized furfural and 5-hydroxymethylfurfural to furoic acid and 5-Hydroxymethyl-2-furoic acid, respectively. The highest yields observed were 88% for furoic acid/furfural and 76% for 5-Hydroxymethyl-2-furoic acid/5-hydroxymethylfurfural. These results are the first demonstration of the capability of G. xylinus to tolerate lignocellulose-derived inhibitors and to convert furan aldehydes.

Pharmacokinetics of the main compounds absorbed into blood after oral administration of Liu Wei Di Huang Wan, a typical combinatorial intervention of Chinese medical formula.[Pubmed:22367633]

J Nat Med. 2013 Jan;67(1):36-41.

Liu Wei Di Huang Wan (LW) has been used as an active Chinese patent formula for "Five Late Syndrome" of Children for thousands of years. Due to the complexity in its chemical constituents, the pharmacokinetics of this formula have not been elucidated clearly, and the understanding of its pharmacological properties has been delayed. Previous studies have identified the constituents absorbed into blood after the oral administration of LW; moreover, 5-Hydroxymethyl-2-furoic acid (HMFA), loganin and paeonol have been proved as surrogate markers. In this study, a rapid validated high-performance liquid chromatography method was developed for determining three marker compounds in plasma. The analysis was performed on a Waters Symmetry Shield RP(18) column with acetonitrile and 0.15% phosphoric acid as the mobile phase, which showed acceptable linearity, intra- and inter-day precision, and accuracy. By using the established method, the pharmacokinetic analysis of LW was carried out. The t (1/2)alpha and t (1/2)beta were 2.62/32.66, 0.46/4.71 and 1.30/23.51 h and the climax times and concentrations were 0.56/683.75, 0.70/2826.11 and 0.62 h/4030.48 ng ml(-1) for HMFA, loganin and paeonol, respectively. Especially, both the absorption and disposition of HMFA were swift (t (1/2) kalpha 0.1 h, t (1/2)alpha 2.62 h), but the elimination was quite slow (t (1/2)beta 32.66 h); this phenomenon reflected the synergetic effect of LW combinatorial intervention and the value of compatibility can be more clearly understood. The pharmacokinetic characters of HMFA, loganin and paeonol not only elucidated the steady and long-lasting pharmacological properties, but they also revealed the practical value of the compatibility of Chinese medical formula.

Demonstration of antioxidant and anti-inflammatory bioactivities from sugar-amino acid maillard reaction products.[Pubmed:22364122]

J Agric Food Chem. 2012 Jul 11;60(27):6718-27.

Maillard reaction products (MRPs), both crude and fractionated, were assessed for antioxidant potential using cell-free, in vitro 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, Fenton reaction induced deoxyribose degradation and oxygen radical absorbance capacity-fluorescein (ORACFL) chemical assays. All MRPs displayed various affinities to scavenge free radicals generated in different reaction media and using different reactive oxygen species (ROS) substrates. High molecular weight MRPs consistently showed the greatest (P < 0.05) antioxidant potential in chemical assays. Repeating these tests in Caco-2 cells with both reactive oxygen and nitrogen (RNS) intracellular assays revealed that the low molecular weight components (LMW) were most effective at inhibiting oxidation and inflammation. In particular, a glucose-lysine (Glu-Lys) mixture heated for 60 min had marked intracellular antioxidant activity and nitric oxide (NO) and interleukin-8 (IL-8) inhibitory activities compared to other MRPs (P < 0.05). Further studies employing ultrafiltration, ethyl acetate extraction, and semipreparative high-performance liquid chromatography (HPLC) produced a bioactive fraction, termed F3, from heated Glu-Lys MRP. F3 inhibited NO, inducible nitric oxide synthetase (iNOS), and IL-8 in interferon gamma (IFN-gamma)- and phorbol ester (PMA)-induced Caco-2 cells. F3 modified several gene expressions involved in the NF-kappaB signaling pathway. Two components, namely, 5-hydroxymethyl-2-furfural (HMF) and 5-Hydroxymethyl-2-furoic acid (HMFA), were identified in the F3 fraction, with an unidentified third component comprising a major portion of the bioactivity. The results show that MRP components have bioactive potential, especially in regard to suppressing oxidative stress and inflammation in IFN-gamma- and PMA-induced Caco-2 cells.

Identification of a new natural vasorelaxatant compound, (+)-osbeckic acid, from rutin-free tartary buckwheat extract.[Pubmed:20873790]

J Agric Food Chem. 2010 Oct 27;58(20):10876-9.

The candidates responsible for vasorelaxation action of rutin-free tartary buckwheat extract (TBSP) were examined in this study. As a result of reversed-phase high-performance liquid chromatography (HPLC) separations, five prominent peaks in the acidic fraction of TBSP were obtained at 260 nm. Among the five collected peaks, we successfully identified four compounds by nuclear magnetic resonance (NMR) and mass spectrometry (MS) measurements: (+)-osbeckic acid as a dimer ([M - H](-) m/z: 371.2 > 184.9 > 140.9), 5-Hydroxymethyl-2-furoic acid, protocatechuic acid, and p-hydroxybenzoic acid. A vascular contractive measurement in 1.0 muM phenylephrine-contracted Sprague-Dawley rat thoracic aorta rings revealed that (+)-osbeckic acid dimer evoked a potent vasorelaxant effect with an EC50 value of 887 muM compared to other isolates (EC50: 5-Hydroxymethyl-2-furoic acid, 3610 muM; protocatechuic acid, 2160 muM; p-hydroxybenzoic acid, no inhibition). Dimeric (+)-osbeckic acid was stable in solutions and at high temperatures, while its degraded peak on the HPLC chromatogram was observed when it was dissolved in dimethyl sulfoxide.

Estimation of dietary intake of 5-hydroxymethylfurfural and related substances from coffee to Spanish population.[Pubmed:20005914]

Food Chem Toxicol. 2010 Feb;48(2):644-9.

5-Hydroxymethylfurfural (HMF) is naturally formed during food processing or cooking activities, giving its ubiquity in the Western diet. HMF could be metabolised to 5-sulfooxymethylfurfural making HMF potentially harmful in an extent unknown at present. Coffee is the main exposure source. Occurrence of HMF, 5-Hydroxymethyl-2-furoic acid (HMFA) and 2-furoic acid (FA) were measured in commercial ground coffee and soluble coffee marketed in Spain. Levels of 110, 625, 1734, 2480 mg HMF/kg were obtained for natural, blend, torrefacto and soluble coffee, respectively, giving four classes significantly different. Soluble coffee showed the largest variability in HMF. Levels of HMFA and FA did not change significantly being about 600 mg/kg. Dietary exposure to HMF coffee to consumption in the total Spanish population was estimated to be 8.57 mg/day by using a deterministic approach. However, median level was recalculated to 5.26 mg HMF/day when specific contribution of each type of ground and soluble coffee in the consumption habits was considered. Resultant value is above of the threshold of concern (1600 microg HMF/day, mTAMDI). A level of 8.57 mg HMF/day in persons with high consumption habits (95th percentile) was calculated for risk assessment.

Dietary exposure to 5-hydroxymethylfurfural from Norwegian food and correlations with urine metabolites of short-term exposure.[Pubmed:18929614]

Food Chem Toxicol. 2008 Dec;46(12):3697-702.

5-Hydroxymethylfurfural (HMF) is formed in carbohydrate-rich food during acid-catalysed dehydration and in the Maillard reaction from reducing sugars. HMF is found in mg quantities per kg in various foods. HMF is mainly metabolised to 5-Hydroxymethyl-2-furoic acid (HMFA), but unknown quantities of the mutagenic 5-sulphoxymethylfurfural (SMF) may also be formed, making HMF potentially hazardous to humans. We determined the HMF content in Norwegian food items and estimated the dietary intake of HMF in 53 volunteers by means of 24h dietary recall. The estimated intakes of HMF were correlated with urinary excretion of HMFA. Coffee, prunes, dark beer, canned peaches and raisins had the highest levels of HMF. The 95th percentile of the estimated daily dietary intake of HMF and the 24h urinary excretion of HMFA were 27.6 and 28.6mg, respectively. Coffee, dried fruit, honey and alcohol were identified as independent determinants of urinary HMFA excretion. Most participants had lower estimated HMF intake than the amount of HMFA excreted in urine. In spite of this there was a significant correlation (r=0.57, P<0.001) between the estimated HMF intake and urinary HMFA. Further studies are needed to reveal alternative sources for HMF exposure.

Suppression of blood lipid concentrations by volatile Maillard reaction products.[Pubmed:18586457]

Nutrition. 2008 Nov-Dec;24(11-12):1159-66.

OBJECTIVE: Although the chemistry of Maillard reaction products (MRPs) in foods has been well studied, few reports on the nutritional characteristics of MRPs in experimental animals and humans have been found. In this study, our interest was focused on the volatile MRPs (vMRPs) found in heated foods. METHODS: To confirm the metabolic oxidations of six methylpyrazines and pyrrole-2-carboxaldehyde to carboxylic acid derivatives in vivo, we administrated these compounds orally to Wistar rats with a single dose of 50 mg/kg. Urine samples were collected over 24 h, followed by determination using high-performance liquid chromatographic procedures. Eight pyrazinoic acids, 2-furoic acid, and 5-Hydroxymethyl-2-furoic acid were administered orally to rats with a single dose of 100 or 300 mg/kg, and blood non-esterified fatty acid and triacylglycerol concentrations were analyzed. RESULTS: Monomethylpyrazine, 2,3-, 2,5-, and 2,6-dimethylpyrazine, trimethylpyrazine, and tetramethylpyrazine were metabolized to a corresponding pyrazinoic acid such as non-substituted pyrazinioic acid, 3-, 5-, or 6-methylpyrazinoic acid, 3,5-, 3,6-, and 5,6-dimethylpyrazinoic acid, and trimethylpyrazinoic acid, in appropriate yields, respectively. Further, pyrrole-2-carboxaldehyde was metabolized to pyrrole-2-carboxylic acid. Non-substituted and 5-methylpyrazinoic acid and 2-furoic and 5-Hydroxymethyl-2-furoic acid showed significant non-esterified fatty acid-lowering effects. 5-Methyl and 6-methylpyrazinoic acid and 2-furoic acid showed significant triacylglycerol-lowering effects. Pyrazinoic acids with methyl substitution at position 3 showed no lipid-lowering effect. CONCLUSION: These results suggest that the vMRPs such as methylpyrazines are metabolized to their corresponding pyrazinoic acids. These vMRPs and their metabolites exhibit blood lipid-lowering effects in rats.

Nematicidal activity of 5-hydroxymethyl-2-furoic acid against plant-parasitic nematodes.[Pubmed:17542490]

Z Naturforsch C J Biosci. 2007 Mar-Apr;62(3-4):234-8.

A nematicide, 5-Hydroxymethyl-2-furoic acid (1), was isolated from cultures of the fungus Aspergillus sp. and its structure was identified by spectroscopic analysis. Compound 1 showed effective nematicidal activities against the pine wood nematode Bursaphelenchus xylophilus and the free-living nematode Caenorhabditis elegans without inhibitory activity against plant growth, but 1 did not show any effective nematicidal activity against Pratylenchus penetrans.

Formation of 5-hydroxymethyl-2-furfural (HMF) and 5-hydroxymethyl-2-furoic acid during roasting of coffee.[Pubmed:17357981]

Mol Nutr Food Res. 2007 Apr;51(4):390-4.

The formation of 5-hydroxymethyl-2-furfural (HMF) and 5-Hydroxymethyl-2-furoic acid (HMFA) during roasting of coffee was studied. At 240 degrees C the maximum concentration of HMF occurs after 3 min with a quick degradation up to 10 min when most of the HMF has disappeared again. Similar to 5-hydroxymethyl-furfural, HMFA is formed in coffee but not in a model system consisting of sucrose, alanine with or without chlorogenic acid. It was shown that HMFA is produced from different precursors than HMF namely glyceraldehyde and pyruvate. The comparison of the laboratory scale roasting with industrial roasting showed that 5-hydroxymethyl-furfural decreases with a higher degree of roasting whereas HMFA did not change. In the laboratory scale experiments, the highest concentration of 5-hydroxymethyl-furfural in coffee (909 microg/g) was obtained after 3 min and the maximum concentration of HMFA after 4 min (150 microg/g). Industrially roasted coffee contained up to 350 microg/g 5-hydroxymethyl-furfural and 140 microg/g HMFA.

Identification and urinary excretion of metabolites of 5-(hydroxymethyl)-2-furfural in human subjects following consumption of dried plums or dried plum juice.[Pubmed:19127754]

J Agric Food Chem. 2006 May 17;54(10):3744-9.

5-(Hydroxymethyl)-2-furfural (I) is a major breakdown product occurring in solutions with high concentrations of fructose and glucose and is present in many fruit juices, in heat-sterilized parenteral solutions, and in baby cereals. The objective of this study was to characterize and identify 5-(hydroxymethyl)-2-furfural metabolites in human subjects following the consumption of dried plum juice and/or dried plums. Subjects were fasted overnight and blood and urine samples were obtained during the day following consumption. Subjects fed the dried plum juice and dried plums consumed 3944 micromol (497 mg) and 531 micromol (67 mg) of I, respectively. Four presumed metabolites of I were detected in the urine of subjects that consumed dried plum juice. They were tentatively identified using HPLC-MS/MS as (1) N-(5-hydroxymethyl-2-furoyl)glycine (III), (2) 5-Hydroxymethyl-2-furoic acid (II), (3) (5-carboxylic acid-2-furoyl)glycine (IV), and (4) (5-carboxylic acid-2-furoyl)aminomethane (V). Total urinary excretion during the 6 h following the consumption of dried plum juice was 168, 1465, 137, and 75 micromoles on the basis of II as a standard for II, III, IV, and V, respectively. The estimated total recovery of I metabolites was 46.2% and 14.2% of the I dose during the first 6 h after consumption of dried plum juice and dried plums, respectively. I seems to be metabolized rapidly to glycine conjugates and other metabolites and excreted in the urine.