The Genetics of Heteromeric Amino Acid Transporters

Abstract

Heteromeric amino acid transporters (HATs) are composed of a heavy (SLC3 family) and a light (SLC7 family) subunit. Mutations in system b(0,+) (rBAT-b(0,+)AT) and in system y(+)L (4F2hc-y(+)LAT1) cause the primary inherited aminoacidurias (PIAs) cystinuria and lysinuric protein intolerance, respectively. Recent developments [including the identification of the first Hartnup disorder gene (B0AT1; SLC6A19)] and knockout mouse models have begun to reveal the basis of renal and intestinal reabsorption of amino acids in mammals.

The draft genome of the grass carp (Ctenopharyngodon idellus) provides insights into its evolution and vegetarian adaptation

“…Comparably, the grass carp genes involved in the GCSD were not only associated with immune-related genes but also with development-related genes ( Fig. 3 and Supplementary Table 15) and were involved in cell proliferation and differentiation (for example, the focal adhesion pathway and the extracellular matrix (ECM)-receptor interaction pathway 30,31 ), nutritional homeostasis (for example, the protein digestion and absorption pathway 32,33 ) and organ size control (for example, the Hippo signaling pathway 34,35 ). Comparison of genes involved in the overview maps of metabolism (reference map ko01100 of the KEGG database) also indicated that grass carp genes involved in the GCSD clustered in carbohydrate metabolism and nucleotide metabolism (Supplementary Fig.…”

Human intestine luminal ACE2 and amino acid transporter expression increased by ACE-inhibitors

“…In small intestine enterocytes and proximal tubule kidney cells, the heterodimer b 0,+ AT-rBAT mediates the apical entry of L-cystine (Feliubadalo et al 1999) and cationic AAs including L-arginine (Arg). Here we show that the basolateral antiporter y + LAT1 that exchanges cationic AAs against neutral AAs and Na + (Palacin et al 2005) is highly expressed all along the human small intestine up to the ileum and thus most likely represents the exit pathway for transcellular cationic AA transport. In contrast, the expression of the other y + L-type transporter y + LAT2 is very low, suggesting that this catalytic subunit is not of functional importance for the transepithelial cationic AA absorption.…”

Novel SLC7A7 large rearrangements in lysinuric protein intolerance patients involving the same AluY repeat

“…About two-thirds of the patients have interstitial changes in chest radiographs, sometimes with acute or chronic respiratory insufficiency that can lead to fatal pulmonary alveolar proteinosis and multipleorgan dysfunction syndrome. 1,7 Recently, some patients with end-stage renal disease have been reported. 8 Further symptoms, such as glomerulonephritis and erythroblastophagia, suggest that the immune system is affected in some patients.…”

“…As a result, plasma levels of dibasic amino acids are low in patients. 1,7,9,10 Arginine and ornithine are intermediates of the urea cycle that provide the carbon skeleton. Their reduced availability is responsible for hyperammonaemia, which is thought to cause acute symptoms such as nausea and vomiting.…”