Investigations into the effect of glyoxylate decarboxylation and transamination on oxalate formation in the rat.
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.
Bais
R
R
Division of Clinical Chemistry, Institute of Medical and Veterinary Science, Adelaide, Australia.
Rofe
A M
AM
Conyers
R A
RA
D019880:Aldehyde-Ketone Transferases; D000818:Animals; D003545:Cysteine / Q000378:metabolism; D003653:Decarboxylation; D006038:Glyoxylates / Q000378:metabolism*; D007656:Ketoglutaric Acids / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000201:enzymology; D008297:Male; D010070:Oxalates / Q000378:metabolism*; D007652:Oxo-Acid-Lyases / Q000302:isolation & purification / Q000378:metabolism; D051381:Rats; D013438:Sulfhydryl Compounds / Q000494:pharmacology
D006038:Glyoxylates; D007656:Ketoglutaric Acids; D010070:Oxalates; D013438:Sulfhydryl Compounds; D019880:Aldehyde-Ketone Transferases; C021414:2-hydroxy-3-oxoadipate synthase; D007652:Oxo-Acid-Lyases; D003545:Cysteine