Bais R, Rofe A M, Conyers R A
Division of Clinical Chemistry, Institute of Medical and Veterinary Science, Adelaide, Australia.
Nephron. 1991;57(4):460-9. doi: 10.1159/000186350.
The decarboxylation and transamination reactions of glyoxylate, which divert this precursor from oxalate formation, have been investigated. Decarboxylation of glyoxylate is synergistic with 2-oxoglutarate and catalysed by 2-oxoglutarate:glyoxylate carboligase which co-chromatographs with the 2-oxoglutarate dehydrogenase complex. The activity is located in the mitochondrial fraction and is probably due to the E1 subunit of the complex. A greater amount of decarboxylation occurs from 2-oxoglutarate than from glyoxylate but the presence of 2-oxoglutarate does not affect oxalate formation from glyoxylate. There is no oxalate formation from 2-oxoglutarate. Studies with rat liver homogenates showed that a number of amino acids can participate in glyoxylate transamination. However, using isolated rat hepatocytes, these reactions did not have a significant effect on oxalate formation from glyoxylate with the exception of cysteine which caused an 80% reduction in oxalate formation. Investigation of this inhibition indicated that it was most likely due to the formation of a cysteine-glyoxylate adduct which makes glyoxylate unavailable for oxidation to oxalate. This cysteine inhibition of oxalate formation was also demonstrated in normal rats and rats made hyperoxaluric by injecting them with either glyoxylate or glycolate. The results indicate that sulphydryl compounds, which can have a therapeutic role as oxalate-lowering agents, may be able to be developed.
已对乙醛酸的脱羧和转氨反应进行了研究，这些反应使该前体物质不再用于草酸盐的形成。乙醛酸的脱羧与2-氧代戊二酸协同进行，并由2-氧代戊二酸：乙醛酸羧化酶催化，该酶与2-氧代戊二酸脱氢酶复合体共色谱。该活性位于线粒体部分，可能归因于该复合体的E1亚基。2-氧代戊二酸发生的脱羧反应比乙醛酸更多，但2-氧代戊二酸的存在并不影响乙醛酸形成草酸盐。2-氧代戊二酸不会形成草酸盐。对大鼠肝脏匀浆的研究表明，许多氨基酸可参与乙醛酸的转氨反应。然而，使用分离的大鼠肝细胞时，除了半胱氨酸使草酸盐形成减少80%外，这些反应对乙醛酸形成草酸盐没有显著影响。对这种抑制作用的研究表明，这很可能是由于形成了半胱氨酸-乙醛酸加合物，使乙醛酸无法氧化成草酸盐。在正常大鼠以及通过注射乙醛酸或乙醇酸而导致高草酸尿症的大鼠中也证实了半胱氨酸对草酸盐形成的抑制作用。结果表明，可作为降低草酸盐药物发挥治疗作用的巯基化合物可能有望被开发出来。
