Disease relevance of Slc25a13

• Slc25a13-knockout mice harbor metabolic deficits but fail to display hallmarks of adult-onset type II citrullinemia [1].

High impact information on Slc25a13

• The absence of citrin leads to a liver-specific, quantitative decrease of argininosuccinate synthetase (ASS), causing hyperammonemia and citrullinemia [1].
• These results suggest that citrin deficiency alone may not be sufficient to produce a CTLN2-like phenotype in mice [1].
• RNA in situ hybridization analysis shows that Slc25a13 is expressed in the branchial arches, as well as the limb and tail buds, during mouse embryonic development (E10.5) [2].
• At E13.5 expression of Slc25a13 is most predominant in epithelial structures, in addition to the forebrain, kidney, and liver [2].
• Aralar1 and citrin are members of the subfamily of calcium-binding mitochondrial carriers and correspond to two isoforms of the mitochondrial aspartate/glutamate carrier (AGC) [3].

Chemical compound and disease context of Slc25a13

• Adult-onset type II citrullinemia (CTLN2) is an autosomal recessive disease caused by mutations in SLC25A13, the gene encoding the mitochondrial aspartate/glutamate carrier citrin [1].

Anatomical context of Slc25a13

• 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 [4].
• These results show that aralar1 is expressed in many more tissues than originally believed and is absent from hepatocytes, where citrin is the only AGC isoform present [3].

Associations of Slc25a13 with chemical compounds

• Expression of three mitochondrial solute carriers, citrin, aralar1 and ornithine transporter, in relation to urea cycle in mice [4].
• Expression of the aspartate/glutamate mitochondrial carriers aralar1 and citrin during development and in adult rat tissues [3].
• Based on the hypothesis that an enhanced glycerol phosphate shuttle activity may be compensating for the loss of citrin function in the mouse, we have generated mice with a combined disruption of the genes for citrin and mitochondrial glycerol 3-phosphate dehydrogenase [5].

Other interactions of Slc25a13

• 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 [4].
• 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 [4].

References