2.A.29.7.2
Citrate/malate exchange carrier CIC (CTP); tricarboxylate carrier (citrate·H⁺/malate, PEP) (SLC25A1). Missense mutations in the SLC25A1 gene lead to an autosomal recessive neurometabolic disorder characterised by neonatal-onset encephalopathy with severe muscular weakness, intractable seizures, respiratory distress, and lack of psychomotor development, often resulting in early death. Majd et al. 2018 measured the effect of all twelve known pathogenic mutations on  transport activity. These mutations abolished transport of citrate completely, or reduced the transport rate by >70%, indicating that impaired citrate transport is the most likely primary cause of the disease. The human citrate carrier predominantly transports citrate, isocitrate, cis-aconitate, phosphoenolpyruvate and malate. Export of citrate from the mitochondrion cannot be fully compensated by other pathways, restricting the cytosolic production of acetyl-CoA that is required for the synthesis of lipids, sterols, dolichols and ubiquinone, which in turn explains the severe disease phenotypes (Majd et al. 2018). The prostate produces and releases large amounts of citrate. Mazurek et al. 2010 cloned the citrate transporter from human prostate epithelial cell plasma membranes.The prostatic carrier is an isoform of the mitochondrial transporter SLC25A1 with a different first exon. The cloned protein is the main prostatic transporter responsible for citrate release.