An Investigation into the Possible Contribution to Oxalogenesis of a Pathway Involving Thiazolidine-2, 4-Dicarboxylate

涉及噻唑烷-2, 4-二羧酸酯的途径对草酰生成的可能贡献的研究

基本信息

批准号：
04454168
负责人：
ICHIYAMA Arata
金额：
$ 4.29万
依托单位：
Hamamatsu University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

项目摘要

In animals, oxalate is a harmful end product of metabolism and is produced primarily from glyoxylate in the liver. Herbivores including man are equipped with serine : pyruvate/alanine : glyoxylate aminotransferase (SPT/AGT) in liver peroxisomes to remove glyoxylate formed in this organelle and thus to prevent overproduction of oxalate. A question arises as to why oxalate should be formed in animals. In the present study, I aimed at elucidating the mechanism of oxalate production from glyoxylate in the liver. A possibility that glycolate oxidase catalyzes consecutive oxidations of glycolate to glyoxylate and further to oxalate has been proven unlikely. Possible contribution of a pathway involving thiazolidine carboxylates formed by condensation of glyoxylate with cysteine or cysteamine has been examined extensively, and was shown to be minor, if any, under the conditions used. The reported peroxisomal localization of lactate dehydrogenase (LDH) activity was most probably due to absorption of this enzyme to peroxisomal membrane. Since the activity of LDH in the liver is very high, however, it was considered to be likely that a portion of glyoxylate released from peroxisomes is oxidized by this cytosolic enzyme to oxalate, although the concentration of glyoxylate in liver cytosol is much lower than that of lactate. In order to investigate this possibility kinetically a simpler model system was looked for and found that a non-pathogenic and non-oxalate-producing mutant of a pathogenic bacteria of rice plant, pseudomonas glumae, produces oxalate when glyoxylate was supplied exogenously. Kinetic studies with the mutant Ps.glumae are under way.

在动物中，草酸盐是一种有害的代谢终产物，主要由肝脏中的乙醛酸盐产生。包括人类在内的食草动物在肝脏过氧化物酶体中配备有丝氨酸：丙酮酸/丙氨酸：乙醛酸转氨酶（SPT/AGT），以去除该细胞器中形成的乙醛酸，从而防止草酸过量产生。一个问题是为什么动物体内会形成草酸盐。在本研究中，我的目的是阐明肝脏中乙醛酸盐产生草酸盐的机制。乙醇酸氧化酶催化乙醇酸连续氧化为乙醛酸并进一步氧化为草酸的可能性已被证明不太可能。涉及由乙醛酸与半胱氨酸或半胱胺缩合形成的噻唑烷羧酸盐的途径的可能贡献已被广泛研究，并且在所使用的条件下被证明是次要的（如果有的话）。所报道的乳酸脱氢酶（LDH）活性的过氧化物酶体定位很可能是由于该酶被过氧化物酶体膜吸收。然而，由于肝脏中LDH的活性非常高，因此认为很可能是从过氧化物酶体释放的部分乙醛酸被这种胞质酶氧化成草酸，尽管肝细胞质中乙醛酸的浓度远低于肝细胞质中的乙醛酸浓度。乳酸。为了从动力学上研究这种可能性，我们寻找了一个更简单的模型系统，并发现水稻病原菌的非致病性和不产生草酸盐的突变体，颖壳假单胞菌，当外源提供乙醛酸盐时会产生草酸盐。突变体 Ps.glumae 的动力学研究正在进行中。