Citrin transporter

Palmieri, L., Pardo, B., del Arco, A. etal. Citrin and aralarl are Ca2+-stimulated aspartate/glutamate transporters in mitochondria. EMBO J. 20 5060-5069, 2001. 

The clinical syndrome of acute neonatal hyper-ammonemic encephalopathy described in the case report represents the classical presentation of a patient with a urea cycle disorder (UCD). It is important to note that this neonatal course represents only the most common and severe presentation of a UCD. This holds true for all the diseases listed in Table 18-1, with the exceptions of arginase (ARG-1) deficiency, which results in progressive spasticity of the lower limbs, and of the mitochondrial membrane transporters citrin and ornithine transporter 1 (ORNT-1). Deficiency of citrin results in adult-onset encephalopathy deficiency of... 

Quantitation of plasma amino acids, especially of citrullinc, is the first step in determining the precise enzyme or transport protein defect in patients with a UCD. If the defect involves N-acetyglutamate synthetase (NAGS), CPSI, or OTC, then plasma citrulline concentration will be low. Marked hypercitrullinemia (>2000 pmol/I.) is seen in argininosuccinate synthetase (AS) deficiency, while moderate increases (>200 pmol/L, normal undetectable) are found in argininosuccinate lyase (AL) and citrin deficiencies. In AL deficiency, the presence of argininosuccinic acid and its anhydrides further distinguishes this disorder. 

Citrin is an aspartate-glutamate antiporter that has a role both in the urea cycle and in the malate aspartate shuttle. It is necessary for the transport of aspartate produced in the mitochondria into the cytosol, where it is used by AS. Its role in the malate-aspartate shuttle is to transport cytosolic NADH reducing equivalents into the mitochondria, where they are used in oxidative phosphorylation. Defects in citrin cause citrullinemia type II. Patients manifest later-onset intermittent hyperammonemic encephalopathy as in HHH syndrome. 

Begum, L., M.A. Jalil, K. Kobayashi, M. lijima, M.X. Li, T. Yasuda, M. Horiuchi, A. Del Arco, J. Satrustegui, and T. Saheki, 2002. Expression of three mitochondrial solute carriers, citrin, aralarl and ornithine transporter, in relation to urea cycle in miee. Biochim. Biophys. Acta 1574,283-292. 

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