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，草酸盐是代谢的有害最终产物，主要由肝脏中的乙二醇产生。包括人在内的食草动物配备丝氨酸：丙酮酸/丙氨酸：肝过氧化物酶体中的甘氨酸氨基转移酶（SPT/AGT），以去除该细胞器中形成的甘氧基，从而防止草酸盐过度生产。关于为什么要在动物中形成草酸盐的问题。在本研究中，我旨在阐明肝脏中草酸盐产生草酸盐的机理。乙醇酸氧化酶将乙二醇连续的氧化催化为乙二醇并进一步催化了草酸盐的可能性。已经对乙二醇羧酸盐与半胱氨酸或cysteamine凝结形成的途径的可能贡献已进行了广泛的检查，并在所使用的条件下被证明是次要的（如果有的话）。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吸收到过氧化物酶体膜上。但是，由于LDH在肝脏中的活性很高，因此认为从过氧化物酶体释放的一部分乙二醇被这种胞质酶氧化为草酸盐，尽管肝细胞质中甘酰胺的浓度远低于乳酸的含量要低得多。为了研究这种可能性，寻找了更简单的模型系统，并发现在水稻植物的致病性细菌（假单胞菌）的非病原性和非恶性产生的突变体时，当外源提供乙醇酸时会产生草酸盐。正在进行突变ps.glumae的动力学研究。