Expression of three mitochondrial solute carriers, citrin, aralar1 and ornithine transporter, in relation to urea cycle in mice.
The present report describes the expression profiles of different tissues and developmental changes of mouse aspartate/glutamate carrier (AGC) genes, Slc25a13 and Slc25a12, and an ornithine transporter gene, Ornt1, in relation to urea cycle enzyme genes, carbamoylphosphate synthetase I (CPS) and argininosuccinate synthetase (ASS). Slc25a13 encodes citrin, recently found to be deficient in adult-onset type II citrullinemia and to function as AGC together with its isoform and product of Slc25a12, aralar1. Citrin was broadly distributed, but mainly in the liver, kidney and heart. Aralar1 was expressed in diaphragm, skeletal muscle, heart, brain and kidney, but not in the liver. These distribution profiles are different from the restricted of Ornt1, ASS and CPS. Citrin, ASS, CPS and Ornt1 showed similar patterns of developmental changes in the liver and small intestine, where they play a role in urea and arginine synthesis. Dietary, hormonal and physical manipulations caused varied changes of CPS, ASS and Ornt1 in the liver, but the change of citrin was not so marked as that of the others. Analysis using RT-PCR and restriction enzyme digestion revealed that the ornithine transporter most expressed is Ornt1, although Ornt2 is detectable at a minute level. All these results suggest that citrin as AGC plays a role in urea synthesis as well as many fundamental metabolic pathways in the liver, and shares metabolic functions with aralar1 in other tissues, and that Ornt1 is an important component in urea synthesis in the liver and in arginine synthesis in the small intestine during the neonatal period.
Begum
Laila
L
Department of Biochemistry, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, 890-8520, Kagoshima, Japan.
Jalil
Md Abdul
MA
Kobayashi
Keiko
K
Iijima
Mikio
M
Li
Meng Xian
MX
Yasuda
Tomotsugu
T
Horiuchi
Masahisa
M
del Arco
Araceli
A
Satrústegui
Jorgina
J
Saheki
Takeyori
T
D000367:Age Factors; D026905:Amino Acid Transport Systems / Q000235:genetics*; D026923:Amino Acid Transport Systems, Basic; D000818:Animals; D000831:Animals, Newborn; D001124:Argininosuccinate Synthase / Q000235:genetics / Q000378:metabolism; D015152:Blotting, Northern; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002222:Carbamoyl-Phosphate Synthase (Ammonia) / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003080:Cold Temperature; D004032:Diet; D007421:Intestine, Small / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins; D051379:Mice; D008809:Mice, Inbred C3H; D008930:Mitochondria, Liver / Q000201:enzymology / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D009206:Myocardium / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000032:analysis / Q000302:isolation & purification; D012333:RNA, Messenger / Q000032:analysis; D013217:Starvation
D026905:Amino Acid Transport Systems; D026923:Amino Acid Transport Systems, Basic; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D012333:RNA, Messenger; C442901:SLC25A15 protein, human; C488998:SLC25A2 protein, human; C491956:Slc25a12 protein, mouse; C492277:Slc25a13 protein, mouse; C488997:Slc25a15 protein, mouse; C459184:Slc7a13 protein, mouse; C041356:ornithine transporter; D012313:RNA; D002222:Carbamoyl-Phosphate Synthase (Ammonia); D001124:Argininosuccinate Synthase