xylitol | 488-81-3

• 物质功能分类: 生物化工 - 糖类化合物 - 单糖
• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: xylitol
• 英文别名: D-xylitol；(2S,4R)-pentane-1,2,3,4,5-pentol
• CAS: 488-81-3
• 化学式: C₅H₁₂O₅
• 分子量: 152.147
• InChiKey: HEBKCHPVOIAQTA-NGQZWQHPSA-N

物化性质

• 熔点：
  102-105 °C
• 沸点：
  194.6°C (rough estimate)
• 密度：
  1.1497 (rough estimate)
• 溶解度：
  DMF：5mg/mL；二甲基亚砜：25mg/mL； PBS（pH 7.2）：5mg/mL
• LogP：
  -3.770 (est)
• 物理描述：
  White, crystalline powder, practically odourless.
• 颜色/状态：
  Monoclinic crystals from alcohol
• 味道：
  Relative sweetness equal to sucrose
• 蒸汽压力：
  2.47X10-3 mm Hg at 25 °C (est)
• 稳定性/保质期：

  Xylitol is stable to heat but is marginally hygroscopic. Caramelization can occur only if it is heated for several minutes near ist boiling point. ... Milled and specialized granulated grades of xylitol have a tendency to cake and should therefore be used within 9 to 12 months. Aqueous xylitol solutions have been reported to be stable, even on prolonged heating and storage.

• 分解：
  Since xylitol is not utilized by most microoragnisms, products made with xylitol are usually safe from fermentation and microbial spoilage.
• 碰撞截面：
  136.3 Ų [M+Na]+ [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]

计算性质

• 辛醇/水分配系数(LogP)：
  -2.5
• 重原子数：
  10
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  101
• 氢给体数：
  5
• 氢受体数：
  5

ADMET

代谢

在哺乳动物中，木糖醇主要在肝脏中被代谢，通过木糖醇脱氢酶和辅因子NAD被氧化成D-木酮糖。D-木酮糖进一步被磷酸化，并通过木酮糖激酶代谢生成木酮糖5-磷酸（Xu5P），这是糖酵解途径非氧化分支的一个中间产物。据报道，Xu5P通过激活蛋白磷酸酶2A（PP2A）_体外_激活核转运和碳水化合物反应元件结合蛋白（ChREBP）的DNA结合活性。因此，ChREBP的激活在体外上调了生脂酶基因的转录，这可能会刺激肝脏中的脂质生成。

In mammals, xylitol is mainly metabolized in the liver where it is oxidized to D-xylulose by xylitol dehydrogenase and cofactor NAD. D-xyluose is further phosphorylated and metabolized by xylulose kinase to xylulose 5-phosphate (Xu5P), an intermediate of the nonoxidative branch of the pentose phosphate pathway. Xu5P is reported to activate nuclear transport and the DNA-binding activities of carbohydrate response element binding protein (ChREBP) via activation of activation of protein phosphatase 2A (PP2A) _in vitro_. Activation of ChREBP thereby upregulates the gene transcription of lipogenic enzymes in vitro, which may stimulate lipogenesis in the liver.

来源:DrugBank

代谢

在人体内静脉注射木糖醇后形成草酸盐的生物化学途径被研究，使用了来自人肝脏的酶。研究结果表明，基于转酮醇酶、果糖激酶和醛缩酶反应的组合代谢途径可以解释在静脉给药木糖醇时产生的葡萄糖、乳酸、三羟酸（D-苏糖酸和D-赤糖酸）和草酸盐（前体）的生成。

The biochemical pathways for formation of oxalate after intravenous injection of xylitol in humans were studied using enzymes derived from human liver. It was concluded that metabolic pathways based on a combination of the transketolase, fructokinase, and aldolase reactions can account for the production of glucose, lactate, tertronates (D-threonic and D-erythronic acids) and oxalate (precursors) during the metabolism of xylitol administered parenterally.

来源:Hazardous Substances Data Bank (HSDB)

代谢

摄入木糖醇后，观察到血清乳酸浓度和乳酸-丙酮酸比例的增加，但增加程度低于葡萄糖。研究者还发现α-二羟基丁酸显著增加。木糖醇的完全代谢产生35个ATP当量，而葡萄糖则产生32个。

After xylitol ingestion increase of serum lactate concentration and lactate-pyruvate ratio was observed, but to a degree less than after glucose. /Investigators/ also found a marked increase of alpha-dihydroxybutyrate. Complete metabolism of xylitol produces 35 equivalents of ATP compared to 32 from glucose.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在人体中，外源性木糖醇通过非特异性的细胞质多醇脱氢酶转化为D-木酮糖。然后磷酸化产生D-木酮糖磷酸，这是葡萄糖醛酸途径和戊糖磷酸途径之间的联系；后者导致甘油醛-3-磷酸和果糖-6-磷酸的形成，这是埃姆登-迈耶霍夫（糖酵解）途径的中间代谢物。因此，木糖醇可以通过葡萄糖-6-磷酸代谢为糖原，或者通过柠檬酸循环代谢为丙酮酸或乳酸，最终转化为CO2。木糖醇主要在肝脏代谢（80%转化为葡萄糖，仅有20%），但也在肾脏、心肌、红细胞、肾上腺、大脑、肺和脂肪组织中有少量代谢。外源性木糖醇可以被大量代谢，静脉注射0.4克/千克/小时或口服40克/天可以将血浆水平提高到最大1.5-16毫克/100毫升。木糖醇的代谢率在健康人、糖尿病或尿毒症患者以及患有肝病的患者中是相同的。

/In humans/ exogenous xylitol enters the pathway by conversion to D-xylulose by a nonspecific cytoplasmic polyol dehydrogenase. Phosphorylation then yields D-xylulose phosphate, the link between the glucuronic acid and the pentose phosphate pathways; the latter leads to the formation of glyceraldehyde-3-phosphate and fructose-6-phosphate, intermediate metabolites of the Embden-Meyerhof (glycolytic) pathway. Thus xylitol can be metabolized via glucose-6-phosphate to glycogen and pyruvate or lactate via the citric acid cycle to CO2. Xylitol is mainly metabolized in the liver (80% to glucose only 20%) but a small amount also in kidney, myocardium, erythrocytes, adrenal, brain, lungs and adipose tissue. Exogenous xylitol can be metabolized in large quantities, intravenously 0.4 gm/kg/hour or 40 g/day orally raises the plasma level to a maximum of 1.5-16 mg/100 mL. The metabolic rate for xylitol is identical in both healthy and diabetic or uraemic patients and patients who suffered from liver diseases.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在以14C-木糖醇进行的人类研究中，90%所摄取的碳原子可以在糖酵解和戊糖磷酸途径的产品和中间体中回收。

In /human/ studies with (14)C-xylitol 90% of C-atoms taken up could be recovered in products and intermediates of the glycolytic and pentose phosphate pathway.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

伴放线放线杆菌是疑似牙周病致病菌之一。伴放线放线杆菌的脂多糖（LPS）是牙周炎发展的关键因素。炎症细胞因子在牙龈组织破坏中起着重要作用，这是牙周炎的特征。巨噬细胞在慢性炎症部位突出，被认为有助于牙周炎的发病机制。木糖醇在这方面表现突出，被广泛认为具有抗龋齿性质。然而，迄今为止，关于木糖醇对牙周炎影响的研究还很少。本研究的目的是确定当RAW 264.7细胞被伴放线放线杆菌LPS刺激时肿瘤坏死因子alpha（TNF-alpha）和白细胞介素-1beta（IL-1beta）的表达，以及木糖醇对LPS诱导的TNF-alpha和IL-1beta表达的影响。LPS处理后培养上清液中TNF-alpha和IL-1beta水平的动力学显示，峰值分别出现在1小时（TNF-alpha）和2到4小时（IL-1beta）。转录因子NF-kappaB也被LPS处理激活。这些细胞因子表达和NF-kappaB的激活被pyrrolidine dithiocarbamate（NF-kappaB的抑制剂）预处理所抑制。用木糖醇预处理抑制了LPS诱导的TNF-alpha和IL-1beta基因表达和蛋白质合成。木糖醇也以剂量依赖性方式抑制了LPS诱导的NF-kappaB的动员。木糖醇还显示了抑制伴放线放线杆菌生长的效果。综上所述，这些发现表明木糖醇可能不仅对龋齿而且对牙周炎都具有良好的临床效果，通过其抑制LPS诱导的炎症细胞因子表达的效果。

Porphyromonas gingivalis is one of the suspected periodontopathic bacteria. The lipopolysaccharide (LPS) of P. gingivalis is a key factor in the development of periodontitis. Inflammatory cytokines play important roles in the gingival tissue destruction that is a characteristic of periodontitis. Macrophages are prominent at chronic inflammatory sites and are considered to contribute to the pathogenesis of periodontitis. Xylitol stands out and is widely believed to possess anticaries properties. However, to date, little is known about the effect of xylitol on periodontitis. The aim of the present study was to determine tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) expression when RAW 264.7 cells were stimulated with P. gingivalis LPS (hereafter, LPS refers to P. gingivalis LPS unless stated otherwise) and the effect of xylitol on the LPS-induced TNF-alpha and IL-1beta expression. The kinetics of TNF-alpha and IL-1beta levels in culture supernatant after LPS treatment showed peak values at 1 hr (TNF-alpha) and 2 to 4 hr (IL-1beta), respectively. NF-kappaB, a transcription factor, was also activated by LPS treatment. These cytokine expressions and NF-kappaB activation were suppressed by pretreatment with pyrrolidine dithiocarbamate (an inhibitor of NF-kappaB). Pretreatment with xylitol inhibited LPS-induced TNF-alpha and IL-1beta gene expression and protein synthesis. LPS-induced mobilization of NF-kappaB was also inhibited by pretreatment with xylitol in a dose-dependent manner. Xylitol also showed inhibitory effect on the growth of P. gingivalis. Taken together, these findings suggest that xylitol may have good clinical effect not only for caries but also for periodontitis by its inhibitory effect on the LPS-induced inflammatory cytokine expression.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

血浆和尿液分数中的草酸盐水平在禁食正常、氧化硫胺素处理（20毫克/千克）和4-脱氧吡哆醇处理（300毫克/千克）的兔子中，在输注木糖醇或葡萄糖2克/千克体重后确定。生物化学测定显示，抗维生素处理的兔子已经诱导出瞬时的硫胺素或吡哆醇缺乏状态。在输注任何一种碳水化合物的最初24小时内，所有组的尿草酸盐水平都保持在正常范围内。氧化硫胺素加速了兔子在输注葡萄糖后出现的暂时的血浆草酸盐浓度升高。输注木糖醇后，血浆草酸盐的升高并不显著高于正常水平。4-脱氧吡哆醇使两种糖的峰值血浆草酸盐水平高于对照组。与木糖醇等效剂量的葡萄糖导致所有组的血浆草酸盐水平高于木糖醇。将[U-(14)C]木糖醇和[U-(14)C]葡萄糖溶液输注到4-脱氧吡哆醇处理的兔子中，显示出给予的放射性碳转化为(14)C草酸盐的转化率为0.01%，并且具有高度稀释的比活度。结果表明，从木糖醇产生的草酸盐可以忽略不计；与木糖醇给药相关的任何毒性并非由草酸盐产生引起。

Oxalate levels in the plasma and urine fractions of fasted normal, oxythiamin treated (20 mg/kg) and 4-deoxypyridoxine treated (300 mg/kg) rabbits were determined following infusion with either xylitol or glucose at a dose of 2 g/kg body weight. Biochemical determinations showed that transient thiamin or pyridoxine deficient states had been induced in the antivitamin treated rabbits. In the first 24 hour following infusion with either carbohydrate, urinary oxalate levels remained within the normal range for all groups. Oxythiamin hastened the appearance of the transient, elevation in plasma oxalate concentrations seen in rabbits after infusion with glucose. After xylitol infusion, the elevation of plasma oxalate was not significantly above normal. 4-Deoxypyridoxine enhanced peak plasma oxalate levels above those of controls for both sugars. Glucose, at an equivalent dose to xylitol, resulted in higher plasma oxalate levels than xylitol for all groups. Infusions of [U-(14)C]xylitol and [U-(14)C]glucose solutions into 4-deoxypyridoxine treated rabbits demonstrated a conversion of the administered radioactive carbon into (14)C oxalate of 0.01% with a high dilution of the specific activity. The results suggest that oxalate production from xylitol is negligible; any toxicity related to xylitol administration is not a consequence of oxalate production.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

（14）C -标记的草酸在Wistar大鼠、CD-1小鼠和NMRI小鼠中的吸收情况进行了研究。将溶液中的草酸通过灌胃的方式给予动物，单独使用水或与0.625 g/kg b.w.的木糖醇一起使用。既使用了适应木糖醇的动物，也使用了之前未接触过木糖醇的动物。适应木糖醇饮食增强了两种品系小鼠对标记（草酸）的吸收和尿液排泄，但在大鼠中并未增强。早期研究表明，喂食高量木糖醇的小鼠膀胱结石的发生率很高，但在大鼠中并未发现。目前的研究结果为膀胱结石形成增加提供了一个可能的解释，即尿液中的草酸盐过饱和。

The absorption of (14)C -labelled oxalic acid was studied in Wistar rats, CD-1 mice and NMRI mice. Oxalic acid in solution was given to the animals by gavage either with water alone or with 0.625 g/kg b.w. of xylitol. Both xylitol-adapted animals and animals not previously exposed to xylitol were used. Adaption to xylitol diets enhanced the absorption and urinary excretion of the label (oxalic acid) in both strains of mice but not in rats. Earlier studies have indicated a high incidence of bladder calculi in mice but not in rats fed high amounts of xylitol. The results of the present study offer one likely explanation for the increased formation of bladder calculi as a result of oversaturation of urine with oxalate.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

木糖醇对其减轻对乙酰苯肼在大鼠体内诱导溶血性贫血的能力进行了研究。动物实验使用两种不同浓度的木糖醇，5%和10%的溶液，总剂量为2g/kg体重，分别以每公斤体重每分钟10mg和20mg木糖醇的输注速率。将两种剂量的对乙酰苯肼（APH），5mg/kg和10mg/kg，作为溶血诱导剂在不同组的大鼠中进行腹腔注射。所有输注木糖醇的大鼠显著减少急性APH诱导的溶血。等渗的5%木糖醇溶液在维持和恢复血液学参数（红细胞压积、血红蛋白浓度、还原型谷胱甘肽（GSH）含量和网织红细胞计数）方面比10%木糖醇溶液更有效。增加的^51Cr-红细胞存活证实了木糖醇的有益效果。在用10mg/kg APH处理后，输注5%木糖醇的大鼠的红细胞存活率（以铬标记表示）从约33%（仅注射APH的大鼠的红细胞存活率）增加到正常大鼠的红细胞存活率的67%。APH处理的大鼠的红细胞比对照组大鼠的红细胞更容易吸收木糖醇。我们的大鼠研究结果提示：（1）木糖醇的非毒性剂量在减轻APH诱导的溶血发作方面是有效的，（2）APH诱导的溶血效应与木糖醇提供的预防效果之间存在剂量关系，（3）药物挑战细胞有效地获取了两到三倍于正常细胞的木糖醇，以补偿细胞的需求，并且（4）尽管血浆中底物的浓度较低（<30mg/dL），但在药物挑战的大鼠红细胞中有足够的木糖醇（55mg/dL）作为木糖醇脱氢酶的底物。这种抗溶血作用可能是通过NADPH的产生实现的，后者维持GSH的水平并保护血红蛋白和其他结构和功能蛋白免受过氧化损伤。

Xylitol was investigated for its ability to ameliorate hemolytic anemia induced by acetylphenylhydrazine in rabbits. Animal experiments were performed using two different concentrations of xylitol, a 5% and a 10% solution with a total dose of 2 g/kg body weight and infusion rates of 10 mg and 20 mg xylitol per kg body weight per minute respectively. Two doses of acetylphenylhydrazine (APH), 5 and 10 mg per kg, were injected intraperitoneally as hemolytic inducers in different groups of rabbits. All the rabbits infused with xylitol showed significantly less acute APH-induced hemolysis. The isotonic 5% xylitol solution was found to maintain and restore the hematological parameters (packed cell volume, hemoglobin concentration, reduced glutathione (GSH) content, and reticulocyte counts) better than the 10% xylitol solution. Increased (51)Cr-red cell survival confirmed the beneficial effect of xylitol. The survival of erythrocytes as represented by chromium-labeling in rabbits infused with 5% xylitol after treatment with 10 mg/kg APH increased from about 33% (the survival of red cells in rabbits injected with APH alone) to 67% of normal rabbits' red cell survival. Erythrocytes in APH-treated animals took up xylitol more readily than erythrocytes from control animals. Our results in rabbits suggest that (1) non-toxic dosage of xylitol is effective in ameliorating the hemolytic episode induced by APH, (2) there is a dose relationship between the hemolytic effect induced by APH and the preventive effect offered by xylitol, (3) drug-challenged cells effectively acquired two to three fold more xylitol to compensate for the cellular needs than that of the normal cells, and (4) sufficient xylitol (55 mg/dL) to act as substrate for xylitol dehydrogenase was recovered intracellularly in drug-challenged rabbit erythrocyte in vivo, in spite of a low plasma (<30 mg/dL) concentration of the substrate. This antihemolytic affect of xylitol is likely accomplished through NADPH generation, which maintains the level of GSH and protects the hemoglobin and other structural and functional proteins against peroxidative damage.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

本研究探讨了口服木糖醇对乙醇消除速率以及乙醇引起的血液中乳酸和丙酮酸浓度变化的影响。在七名健康男性受试者中进行实验，木糖醇（1.0克/千克体重）口服给药，而乙醇（0.8克/千克体重）静脉给药。在对照实验中，用葡萄糖代替木糖醇。结果显示，木糖醇对乙醇消除速率或乙醇引起的血液乳酸浓度增加没有显著影响。木糖醇也没有影响乙醇引起的乳酸/丙酮酸比值的变化。研究表明，口服给药后木糖醇在肝脏中的低浓度可能是其无效的原因。乙醇使血液中木糖醇的浓度增加了5-10倍，这很可能是由于乙醇通过降低肝脏的氧化还原状态来抑制肝脏中木糖醇的氧化。这一发现的临床意义尚不清楚。

The effects of oral administration of xylitol on the rate of ethanol elimination and on the ethanol-induced changes in blood concentrations of lactate and pyruvate were studied in seven healthy male subjects. Xylitol (1.0 g/kg body weight) was administered orally and ethanol (0.8 g/kg body weight) intravenously. In the control experiments glucose was given instead of xylitol. Xylitol had no significant effect on the rate of ethanol elimination or on the ethanol-induced increase in the blood lactate concentration. The ethanol-induced changes in the lactate/pyruvate ratio were not affected by xylitol. It is suggested that the ineffectiveness of xylitol is due to its low concentration in the liver after oral administration. Ethanol induced a 5-10-fold increase in the blood concentration of xylitol. This is most probably due to inhibition of xylitol oxidation in the liver by the ethanol-induced reduction in the hepatic redox state. The clinical significance of this finding is unknown.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

• 吸收

木糖醇通过被动扩散在小肠中被吸收，吸收速度较慢。

Xylitol is absorbed in the small intestine via passive diffusion with a slow absorption rate.

来源:DrugBank

吸收、分配和排泄

• 消除途径

无药代动力学数据可用。

No pharmacokinetic data available.

来源:DrugBank

吸收、分配和排泄

• 分布容积

无药代动力学数据可用。

No pharmacokinetic data available.

来源:DrugBank

吸收、分配和排泄

• 清除

无药代动力学数据可用。

No pharmacokinetic data available.

来源:DrugBank

吸收、分配和排泄

五名健康的人类志愿者（两名男性和三名女性）在早餐时饮用了一种含有30克木糖醇的橙味饮料。在给药前，收集了24小时的尿液，并在木糖醇剂量后的24小时内继续收集。在收集期间，不允许食用富含草酸盐的食物。没有检测到尿液中草酸排泄的显著变化。

Five healthy human volunteers (two males and three females) received an orange flavored drink containing 30 g xylitol with breakfast. Before dosing, urine was collected for 24 hr and collections were continued 24 hr after the dose of xylitol. During the collection period no foods rich in oxalate were permitted. No significant changes in urinary oxalate excretion could be detected.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• TSCA：
  Yes
• 危险品标志：
  Xi
• 安全说明：
  S24/25
• 危险类别码：
  R36/37/38
• WGK Germany：
  3
• 海关编码：
  29054990

制备方法与用途

用途

阿东糖醇用于实验室生化试剂、中药对照品和标准品等。

生物活性

ribitol（阿东糖）是一种戊糖醇结晶，通过核糖还原形成，在Adonis vernalis植物中自然发生。

靶点

Human Endogenous Metabolite (人类内源性代谢物)

体外研究

Ribitol 是一种从 Adonis vernalis 植物鉴定出来的戊糖醇结晶。在10% NFSM悬浮液中的 Ribitol 对甘油保护效果的增强程度为1.45到2.18倍，0.75 M 的 Ribitol 具有最佳的抗冻效果。在对包括 S. lactis T164 在内的13种检测生物的研究中，有11种受 Ribitol 保护的程度大于80%，Ribitol 对冷冻干燥过程中的乳酸菌具有很强的保护效果。