塑化劑有BBP、DBP、DEHP、DNOP、DINP、DIDP、DMP、DEP、DIBP
不過都是鄰苯二甲酸+酯的結構
Degradation of these esters proceeds by the action of esterases to form phthalate isomers,
which are converted to dihydroxylated intermediates
by specific and inducible phthalate isomer dioxygenases.
這些酯的降解通過【酯酶】的作用進行,以形成鄰苯二甲酸酯異構體,
其通過特異性和誘導型鄰苯二甲酸酯異構體【雙加氧酶】轉化為二羥基化中間體。
鄰苯二甲酸酯在體內的代謝過程?
鄰苯二甲酸酯在體內的代謝至少經歷兩個步驟:
1. 鄰苯二甲酸酯被水解為初級代謝物,即鄰苯二甲酸單酯(phthalates monoester)。
通常外源性物質經過體內代謝後代謝產物的毒性會降低,
然而鄰苯二甲酸酯體外與體內實驗研究發現,鄰苯二甲酸酯代謝為單酯時生物活性反而增高,毒性增加。
2. 鄰苯二甲酸單酯經肝臟第二階段的排毒作用(葡萄糖醛酸化反應,glucuronidation)產生親水性的葡糖苷酸(glucuronide),結合物排出體外。
An esterase is a hydrolase enzyme that splits esters into an acid and
an alcohol in a chemical reaction with water called hydrolysis.
酯酶是一種水解酶,其在與水的化學反應中將酯分解成酸和醇,稱為水解。
加氧酶的酶反應需要還原型輔因子,如FAD(維他命B2)、NADP(維他命B3)、
那一開始降解塑化劑鄰苯二甲酸+酯結構的酯酶呢?
A gene annotated as “carboxylesterase” with a 1,464-long ORF that encoded 487 amino acid
proteins was found and we named it as CarEW.
發現一個註釋為“羧酸酯酶”的基因,其編碼487個氨基酸的蛋白質的1,464長ORF,我們將其命名為CarEW。
CarEW is capable of hydrolyzing DiBP to MiBP(monoisobutyl phthalate) and PTH(phthalic acid).
CarEW can completely degrade DiBP to PTH over a long duration under ambient temperatures.
CarEW能夠將DiBP(塑化劑的一種)水解成MiBP(鄰苯二甲酸單異丁酯)和PTH(鄰苯二甲酸)。在環境溫度下,
CarEW可以在長時間內完全降解DiBP至PTH。
The effect of different metal ions on CarEW activity was examined by addition of each metal ion
into the reaction mixture at a final concentration of 1.0 mM.
The results are presented in Table 2.
Fe2+, Hg2+, Ag+, and Mn2+ had a strong inhibitory effect (50%–60% inhibition);
Li+ and Co2+ had no apparent effect on enzyme activity (data not shown); whereas K+, Cu2+, Na+,
and Zn2+ activated CarEW.
CarEW activity was moderately inhibited by Ca2+, Ni2+, Ba2+,
and Mg2+ (17%–30% inhibition).
Chemical agents such as CTAB (0.1%) strongly inhibited CarEW
(7.8% residual activity), and inhibition by DTT (1 mM), Triton X-100 (2%) and SDS (0.1%)
were approximately 63%, 48%, and 40%, respectively.
Urea (0.1 M) and EDTA (1 mM)
exhibited moderate inhibitory effects (residual activities from 77% to 85%).
Tween 80 had little effect on the enzyme activity.
K +,Cu2+(銅),Na+和Zn2+(鋅)活化了CarEW(重點只有這一句)
以上的意思是:Cu2+(銅)和Zn2+(鋅)活化(啟動)了可以降解塑化劑的羧酸酯酶,名為CarEW。
The results strongly suggest that multiple carboxylesterase isozymes were induced
in mouse hepatic microsomes by dietary exposure to DEHP.
結果強烈地表明,通過膳食暴露於DEHP,在小鼠肝微粒體中誘導多種羧酸酯酶同功酶。
這句話是說:
人體受到塑化劑感染,肝臟就會啟動多種與降解塑化劑的羧酸酯酶同樣功能的酶。
In this study, we examined the hydrolytic metabolism of dimethyl phthalate (DMP),
dibutyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP) by rat tissue microsomes.
We found that carboxylesterase and lipase contribute differently to these activities.
在本研究中,我們通過大鼠組織微粒體檢查了
鄰苯二甲酸二甲酯(DMP),鄰苯二甲酸二丁酯(DBP)和鄰苯二甲酸二(2-乙基己基)酯(DEHP)的水解代謝。
我們發現羧酸酯酶和脂肪酶對這些活動有不同的貢獻。
這句話是說:羧酸酯酶和脂肪酶
對
DMP、
DBP
有不同的貢獻。
DEHP can damage female rats and fetal rats in gestation period.
Zinc supplied before pregnancy can relieve the influence by DEHP.
DEHP可以在妊娠期損傷雌性大鼠和胎鼠。懷孕前提供的鋅可以緩解DEHP的影響。
We previously demonstrated that rats exposed to the peroxisome proliferator (PP)
diethylhexylphthalate (DEHP) had reduced serum ceruloplasmin (CP) oxidase activity
我們以前表明暴露於過氧化物酶體增殖物(PP)二乙基己基鄰苯二甲酸酯(DEHP)的大鼠血清
銅藍蛋白(CP)氧化酶活性降低
抗壞血酸(維它命C)、銅和鐵進行反應。
上述表明降解塑化劑不能缺銅、鋅。
但是這些酶(酵素)的活性部位也需要胺基酸