Control of oxalate formation from L-hydroxyproline in liver mitochondria
Control of oxalate formation from L-hydroxyproline in liver mitochondria
复制标题
DOI：
10.1097/01.asn.0000059310.67812.4f
复制
发表时间：
2003-04-01
影响因子：
13.6
通讯作者：
Ogawa, Y
中科院分区：
文献类型：
--
作者：
Takayama, T;Fujita, K;Ogawa, Y
丝氨酸：丙酮酸/丙氨酸：乙醛酸氨基转移酶（SPT/AGT）主要位于食肉动物的线粒体中，而它完全存在于食草动物和人类的过氧化物酶体中。在大鼠肝脏中，这两种细胞器均存在SPT/AGT，胰高血糖素仅显著诱导线粒体酶。虽然SPT/AGT是一种双功能酶，参与l -丝氨酸和乙醛酸盐的代谢，但其对l -丝氨酸代谢的贡献不依赖于线粒体或过氧化物酶体的定位（Xue HH et al., journal of biological Chem, 274: 16028-16033, 1999）。因此，物种特异性和食物习惯依赖性的细胞器分布可能是乙醛酸盐形成亚细胞部位的适当代谢所必需的。乙醇酸和l -羟脯氨酸分别在过氧化物酶体和线粒体中形成乙醛酸盐。本研究发现，大剂量的l -羟脯氨酸或乙醇酸给予大鼠时，尿中草酸的排泄明显增加。当胰高血糖素诱导线粒体SPT/AGT时，l -羟脯氨酸生成草酸显著减少，而乙醇酸生成草酸未显著减少。胶原中羟脯氨酸含量为10 ~ 13%，占动物总蛋白的30%左右；因此，这些结果表明，在食肉动物中，线粒体SPT/AGT的一个重要作用是将l -羟脯氨酸衍生的乙醛盐原位转化为甘氨酸，防止有害的溢出产生草酸盐。
Serine:pyruvate/alanine:glyoxylate aminotransferase (SPT/AGT) is largely located in mitochondria in carnivores, whereas it is entirely found within peroxisomes in herbivores and humans. In rat liver, SPT/AGT is found in both of these organelles, and only the mitochondrial enzyme is markedly induced by glucagon. Although SPT/AGT is a bifunctional enzyme involved in the metabolism of both L-serine and glyoxylate, its contribution to L-serine metabolism is independent of mitochondrial or peroxisomal localization (Xue HH et al., J Biol Chem 274: 16028-16033, 1999). Therefore, the species-specific and food habit-dependent organelle distribution might be required for proper metabolism of glyoxylate at the subcellular site of its formation. Glyoxylate formation from glycolate and that from L-hydroxyproline have been shown to occur in peroxisomes and mitochondria, respectively. The present study found that urinary excretion of oxalate was markedly increased when a large dose of L-hydroxyproline or glycolate was administered to rats. Oxalate formation from L-hydroxyproline but not that from glycolate was significantly reduced when mitochondrial SPT/AGT had been induced by glucagon. The hydroxyproline content of collagen is 10 to 13%, and collagen accounts for about 30% of total animal protein; therefore, these results suggest that an important role of mitochondrial SPT/AGT in carnivores is to convert L-hydroxyproline-derived glyoxylate into glycine in situ, preventing undesirable overflow into the production of oxalate.