ホモゲンチジン酸
ホモゲンチジン酸 · 2,5-ジヒドロキシフェニル酢酸 · ホモゲンチシン酸 · アルキャプトン · (2,5-ジヒドロキシフェニル)酢酸 · 2,5-ジヒドロキシベンゼン酢酸 · アルカプトン · 2,5-ジオキシ-α-トルイル酸
識別子と物理属性
| CAS No. | 451-13-8 |
|---|---|
| 分子式 | C8H8O4 |
| 平均分子量 | 168.15 g/mol |
| 単同位体質量 | 168.04225874 g/mol |
| SMILES | O=C(O)Cc1cc(O)ccc1O |
| InChIKey | IGMNYECMUMZDDF-UHFFFAOYSA-N |
| PubChem CID | 780 |
| ChEBI | CHEBI:44747 |
| EC No. | 207-192-7 |
| DTXSID | DTXSID1060005 |
| 現地名 | ホモゲンチジン酸 |
化学・物理的性質
| XLogP | 0.5 |
|---|---|
| 極性表面積 | 77.8 |
| 水素結合供与体数 | 3 |
| 水素結合受容体数 | 4 |
| 回転可能結合数 | 2 |
| 重原子数 | 12 |
| 形式電荷 | 0 |
| 複雑度 | 168 |
| 物質分類 | Other Classes -> Organic Acids |
| 医薬品 | Pharmaceuticals -> Metabolite of DiclofenacPharmaceuticals -> Listed in ZINC15 |
| LogP（分配係数） | 0.86 |
| 溶解度 | 850 mg/mL at 25 °Cメタノールに可溶。非常にかすかな濁り |
| 融点 | 153 °C150-152 °C (lit.) |
| 蒸気圧 | 0.00000082 [mmHg] |
| Physical Description | Beige crystalline solid[Sigma-Aldrich MSDS] |
| Collision Cross Section | 132.4 Ų [M-H]- [CCS Type: DTMethod: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]135.9 Ų [M+H-H2O]+ [CCS Type: DTMethod: single field calibrated with Agilent tune mix (Agilent)]132.7 Ų [M-H]- |
| 沸点 | 257.07°C (rough estimate) |
| 密度 | 1.3037 (rough estimate) |
| 屈折率 | 1.5090 (estimate) |
| 貯蔵条件 | 2-8°C |
| pKa（酸解離定数） | 4.4(at 25℃) |
| 外観・状態 | 結晶性 |
| 色 | オフホワイトからタン |
| Merck | 14,4737 |
| BRN | 2692860 |
| 主な用途 | 食品および飲料 |
| InChI | 1S/C8H8O4/c9-6-1-2-7(10)5(3-6)4-8(11)12/h1-3,9-10H,4H2,(H,11,12) |
| InChIKey | IGMNYECMUMZDDF-UHFFFAOYSA-N |
| SMILES | OC(=O)Cc1cc(O)ccc1O |
| LogP（分配係数） | 0.860 |
| CAS データベース | 451-13-8(CAS DataBase Reference) |
| EPAの化学物質情報 | Benzeneacetic acid, 2,5-dihydroxy- (451-13-8) |
化学的特性
off-white to tan crystals or crystalline powder
安全性と法規制
| GHS 分類 | WarningH315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 40 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| 有害性の概要 | Causes changes in urine composition in 5-day intermittent intraperitoneal studies of rats[RTECS] A skin and strong eye irritant[Sigma-Aldrich MSDS] |
| Hazard Classes and Categories | Skin Irrit. 2 (100%) |
| Treatment | Apart from treatment of the complications (such as pain relief using NSAIDs and joint replacement for the cartilage damage), vitamin C has been used to reduce the ochronosis and lowering of the homogentisic acid levels may be attempted with a low-protein diet. Recently the drug nitisinone has been found to suppress homogentisic acid production. Nitrisinone inhibits the enzyme, 4-hydroxyphenylpyruvate dioxygenase, responsible for converting tyrosine to homogentisic acid, thereby blocking the production and accumulation of homogentisic acid. Nitisinone treatment has been shown to cause a 95% reduction in plasma and urinary homogentisic acid. |
| 健康影響 | Homogentisic acid is only toxic under chronic exposure. One of the first symptoms of alkaptonuria is darkening of urine on standing (due to the oxidation of homogentisic acid). In most pediatric patients, darkening of urine is the only feature suggesting alkaptonuria. Most patients are usually asymptomatic until age 30. Scleral pigmentation usually starts around age 30. Skin pigmentation becomes obvious by the time patients reach age 40. One of the first sites to be affected is the ear cartilage. There may be discoloration of the forehead, cheeks, axilla, genitalia, palms, nails and soles. Ochronotic arthropathy starts around the 4th decade. Weight-bearing joints like the knees and the intervertebral joints in the spine, as well as the shoulder joints, are involved, with narrowing of joint spaces and disc calcifications. Arthritis is the only disabling effect of this condition and occurs in almost all patients as age advances. Ochronotic arthropathy can be so severe as to require total joint replacement. Pigment deposits can be seen in the larynx, tonsils, esophagus, dura mater, eardrums, trachea, and bronchi. Aortic or mitral valvulitis, calcification of coronary arteries and atherosclerotic plaques are seen after the age of 50 years. |
| 毒性の概要 | Extremely high levels of homogentisic acid are found in patients with the inborn error of metabolism (IEM) called Alkaptonuria. Homogentisic acid spontaneously undergoes oxidation into benzoquinone acetic acid (BQA), which polymerizes forming plasma soluble melanins (PSM). The PSM darkens many tissues (ochronosis - as the tissue looks like ochre), and produces widespread degenerative changes in cartilage and other connective tissues, joints, blood vessels, heart valves and the kidneys. Ochronotic tissue is stiff and unusually brittle. The accumulation of PSM in chondrocytes (the cells that form cartilage) leads to profound alterations in the levels of proteins involved in cell defense, protein folding, and cell organization. An increased post-translational oxidation of proteins, which also involved high molecular weight protein aggregates, has been found to be particularly evident in chondrocytes from patients with alkaptonuria. |
| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
| 水環境危害等級（WGK） | 3 |
| TSCA 収載状態 | TSCA listed |
| RTECS 番号 | AH0589000 |
| 税関コード | 29182900 |
| 危険文句（R） | 36/37/38 |
| 危険表示 | Xi |
| 安全措置（S） | 26-36 |
| 貯蔵分類 | 13 - Non Combustible Solids |
用途
解説
ホモゲンチシン酸．人体内でフェニルアラニンやチロシンが分解されるときの中間生成物として生じ，正常人体内では，さらにフマル酸とアセト酢酸とになってクエン酸サイクルに入るが，アルカプトン尿症患者の尿中にはこのまま多量に排出される．水から再結晶したものは1分子の結晶水を含み，放置すると風解して無水物(融点152 ℃)となる．100 ℃ 以上に加熱するとラクトンを形成する．エタノール，エーテル，水など可溶．還元力があり，フェーリング液を還元する．
使用
Homogentisic acid may be used as an analytical reference standard for the quantification of the analyte in the following:Urine matrices using reversed-phase liquid chromatography tandem mass spectrometry (LC-MS/MS).Strawberry tree honey samples using reversed phase-high performance liquid chromatography (RP-HPLC) and ion chromatography (IC).It may also be used as an internal standard for the determination of ascorbic acid (AA) and uric acid (UA) in human plasma samples using high-pressure liquid chromatography–electrochemical detection (HPLC–ECD).
一般的な説明
Homogentisic acid (HGA) is an intermediate formed during the catabolism of phenylalanine and tyrosine. Alkaptonuria, a metabolic disorder, is characterized by high levels of HGA in serum and urine due to the deficiency of the enzyme homogentisic acid oxidase, which is involved in the degradation of HGA.
製法・合成法
純化方法
Crystallise homogentisic acid from EtOH/CHCl3 or H2O (solubility is 85% at 25o). [Beilstein 10 IV 1506.]