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

在动物体内，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了丝氨酸：丙酮酸/丙氨酸：乙醛酸氨基转移酶（SPT/AGT），以去除在该细胞器中形成的乙醛酸，从而防止草酸过量产生。问题是为什么草酸盐会在动物体内形成。在本研究中，我旨在阐明肝脏中乙醛酸盐产生草酸的机制。乙醇酸氧化酶催化乙醇酸连续氧化生成乙醛酸盐并进一步氧化生成草酸盐的可能性已被证明是不可能的。由乙醛酸盐与半胱氨酸或半胱胺缩合形成的噻唑烷羧酸盐的途径可能起的作用已被广泛研究，并且在使用的条件下，如果有的话，被证明是次要的。据报道，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，由于肝脏中乳酸脱氢酶的活性非常高，因此人们认为可能是过氧化物酶体释放的一部分乙醛酸盐被这种胞质酶氧化为草酸盐，尽管肝胞质中乙醛酸盐的浓度远低于乳酸盐的浓度。为了从动力学角度研究这种可能性，我们寻找了一个更简单的模型系统，并发现当外源提供乙醛酸盐时，水稻病原菌glumae的非致病性和不产生草酸盐的突变体产生草酸盐。对突变株Ps.glumae的动力学研究正在进行中。

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.