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Abstract
Reabsorption of amino acids is an important function of the renal proximal tubule. pH-dependent amino acid transport has been measured previously using rabbit renal brush-border membrane vesicles (BBMV). The purpose of this investigation was to determine whether this pH-dependent uptake represents H+/amino acid cotransport via a PAT1-like transport system. The rabbit PAT1 cDNA was isolated (2296bp including both 5′ and 3′ untranslated regions and poly(A) tail) and the open reading frame codes for a protein of 475 amino acids (92% identity to human PAT1). Rabbit PAT1 mRNA was found in all tissues investigated including kidney. When expressed heterologously in a mammalian cell line, rabbit PAT1 mediates pH-dependent, Na+-independent uptake of proline, glycine, l-alanine and α-(methylamino)isobutyric acid. Proline uptake was maximal at pH 5.0 (Km 2.2±0.7 mM). A transport system with identical characteristics (ion dependency, substrate specificity) was detected in rabbit renal BBMV where an overshoot was observed in the absence of Na+ but in the presence of an inwardly directed H+ gradient. In the presence of Na+ and under conditions in which PAT1 transport function was suppressed, a second proline uptake system was detected that exhibited functional characteristics similar to those of the IMINO system. The functional characteristics of rabbit PAT1 in either mammalian cells or renal BBMV suggest that PAT1 is the low-affinity transporter of proline, glycine and hydroxyproline believed to be defective in patients with iminoglycinuria.
| Acronyms | ||
| α-aminoisobutyric acid | = | AIB |
| brush-border membrane vesicles | = | BBMV |
| γ-aminobutyric acid | = | GABA |
| human retinal pigment epithelial cell | = | HRPE |
| α-(methylamino)isobutyric acid | = | MeAIB |
| glyceraldehyde-3-phosphate dehydrogenase | = | G3PDH |
| lysosomal amino acid transporter 1 | = | LYAAT1 |
| Na+/H+ exchanger 3 | = | NHE3 |
| Online Mendelian Inheritance in Man | = | OMIM |
| H+-coupled amino acid transporter 1 | = | PAT1 |
| reverse-transcriptase polymerase chain reaction | = | RT-PCR |
| solute carrier family 36 | = | SLC36 |
| solute carrier family 36 member 1 | = | SLC36A1 |
| Acronyms | ||
| α-aminoisobutyric acid | = | AIB |
| brush-border membrane vesicles | = | BBMV |
| γ-aminobutyric acid | = | GABA |
| human retinal pigment epithelial cell | = | HRPE |
| α-(methylamino)isobutyric acid | = | MeAIB |
| glyceraldehyde-3-phosphate dehydrogenase | = | G3PDH |
| lysosomal amino acid transporter 1 | = | LYAAT1 |
| Na+/H+ exchanger 3 | = | NHE3 |
| Online Mendelian Inheritance in Man | = | OMIM |
| H+-coupled amino acid transporter 1 | = | PAT1 |
| reverse-transcriptase polymerase chain reaction | = | RT-PCR |
| solute carrier family 36 | = | SLC36 |
| solute carrier family 36 member 1 | = | SLC36A1 |