Control of oxalate formation from L-hydroxyproline in liver mitochondria.
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.
Takayama
Tatsuya
T
Department of Urology, Research Equipment Center, Hamamatsu University School of Medicine, Hamamatsu, Japan. takayama@hama-med.ac.jp
Fujita
Kimio
K
Suzuki
Kazuo
K
Sakaguchi
Michiko
M
Fujie
Michio
M
Nagai
Erina
E
Watanabe
Shinya
S
Ichiyama
Arata
A
Ogawa
Yoshihide
Y
D000818:Animals; D005934:Glucagon / Q000378:metabolism; D006038:Glyoxylates / Q000378:metabolism* / Q000652:urine; D006909:Hydroxyproline / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D010070:Oxalates / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000637:Transaminases / Q000378:metabolism
D006038:Glyoxylates; D010070:Oxalates; D005934:Glucagon; D000637:Transaminases; C019635:Alanine-glyoxylate transaminase; C022638:serine-pyruvate aminotransferase; C031150:glyoxylic acid; D006909:Hydroxyproline