Intestinal Amino Acid Transport Research Articles

Prevalence of cystinuria among elementary schoolchildren in Eskisehir, Turkey

Cystinuria is an inherited transport disorder due to defects in intestinal and renal transport of cystine and dibasic amino acids. Early diagnosis is required for some general and specific treatments because cystinuric patients have an increased risk of recurrent urinary stone formation. The prevalence of cystinuria varies widely in different countries. The aim of this study is to determine the prevalence of cystinuria among schoolchildren in Eskisehir, a central Anatolian city in Turkey. The sodium cyanide-nitroprusside spot test was applied to the first morning urine samples from 8260 schoolchildren (4087 female, 4173 male, aged between 6 and 12 years). Urine and blood amino acids were determined with paper chromatography and special cystine-homocystine chromatography were performed if a child had a positive spot-test result. Urinary cystine levels of two children were measured quantitatively. Spot-test results were positive in four students. Increased levels of cystine and dibasic amino acids in the urine were determined with paper chromatography and cystine spots were also detected with special cystine-homocystine chromatography for these four students. Urinary cystine levels were elevated in two children whose urine could be studied. The prevalence of cystinuria in this study was 1:2065. There was no history or symptoms related to urolithiasis in these students. The prevalence of cystinuria in this study is higher than many other countries. Patients in Turkey with urinary stones or with symptoms related to urolithiasis must also be investigated for cystinuria.

Human solute carrier SLC6A14 is the β‐alanine carrier

The β-alanine carrier was characterized functionally in the 1960s to 1980s at the luminal surface of the ileal mucosal wall and is a Na+- and Cl−-dependent transporter of a number of essential and non-essential cationic and dipolar amino acids including lysine, arginine and leucine. β-Alanine carrier-like function has not been demonstrated by any solute carrier transport system identified at the molecular level. A series of experiments were designed to determine whether solute carrier SLC6A14 is the molecular correlate of the intestinal β-alanine carrier, perhaps the last of the classical intestinal amino acid transport systems to be identified at the molecular level. Following expression of the human SLC6A14 transporter in Xenopus laevis oocytes, the key functional characteristics of the β-alanine carrier, identified previously in situ in ileum, were demonstrated for the first time. The transport system is both Na+ and Cl− dependent, can transport non-α-amino acids such as β-alanine with low affinity, and has a higher affinity for dipolar and cationic amino acids such as leucine and lysine. N-methylation of its substrates reduces the affinity for transport. These observations confirm the hypothesis that the SLC6A14 gene encodes the transport protein known as the β-alanine carrier which, due to its broad substrate specificity, is likely to play an important role in absorption of essential nutrients and drugs in the distal regions of the human gastrointestinal tract.

Further evidence for allelic heterogeneity in Hartnup disorder

Hartnup disorder is an autosomal recessive impairment of amino acid transport in kidney and intestine. Mutations in SLC6A19 have been shown to cosegregate with the disease in the predicted recessive manner; however, in two previous studies (Seow et al., Nat Genet 2004;36:1003-1007; Kleta et al., Nat Genet 2004;36:999-1002), not all causative alleles were identified in all affected individuals, raising the possibility that other genes may contribute to Hartnup disorder. We have now investigated six newly acquired families of Australian and Canadian (Province of Quebec) origin and resequenced the entire coding region of SLC6A19 in families with only a single disease allele identified. We also studied one American family in whom no mutations had been identified in a previous study (Kleta et al., Nat Genet 2004;36:999-1002). We have identified seven novel mutations in SLC6A19 that show functional obliteration of the protein in vitro, explaining Hartnup disorder in all reported families so far. We demonstrate that Hartnup disorder is allelically heterogeneous with two mutated SLC6A19 alleles, whether identical or not, necessary for manifestation of the characteristic aminoaciduria in affected individuals. This study resolves the previous hypothesis that other genes contribute to the Hartnup phenotype.

Genomic regulation of intestinal amino acid transporters by aldosterone

Overexpression of renal LAT2, a Na+ -independent L-amino acid transporter, in spontaneous hypertensive rats (SHR) is organ specific and precedes the onset of hypertension (Pinho et al., Hypertension, 42:613-618, 2003). However, the expression of LAT2 correlates negatively with plasma aldosterone levels after high sodium intake (Pinho et al., Am J Physiol Ren Physiol 292:F1452-F1463, 2007). The present study evaluated the expression of Na+ -independent LAT1, LAT2, and 4F2hc and Na+ -dependent ASCT2 amino acid transporters in the intestine of normotensive Wistar rats chronically treated with aldosterone. In conditions of high salt intake, to keep endogenous aldosterone to a minimum, rats were implanted with aldosterone or spironolactone tablets. In aldosterone-treated and aldosterone + spironolactone-treated rats, aldosterone plasma levels were increased by fourfold. At the protein level, aldosterone treatment significantly increased LAT1 (62%), LAT2 (49%), 4F2hc (48%), and ASCT2 (65%) expression. The effect of aldosterone upon LAT1, LAT2, 4F2hc, and ASCT2 protein abundance was completely reversed by spironolactone. Aldosterone significantly increased intestinal LAT2 and 4F2hc mRNA levels (27% and 35% increase, respectively), with no changes in LAT1 and ASCT2 transcript levels. In conclusion, increases in intestinal Na+ -independent LAT1 and LAT2 and Na+ -dependent ASCT2 transcript and protein abundance during chronic treatment with aldosterone occur through a spironolactone-sensitive genomic mechanism.

PI3-Kinase-dependent electrogenic intestinal transport of glucose and amino acids

Intestinal glucose and amino acid transport is stimulated by the serum- and glucocorticoid-inducible kinase isoforms SGK1, SGK2, and SGK3 and protein kinase B which are, in turn, stimulated following activation of the phosphoinositol-3 kinase (PI3 kinase). The present study has been performed to explore whether pharmacological inhibition of the PI3 kinase affects electrogenic jejunal transport of glucose and amino acids. In Ussing chamber experiments, glucose (20 mM), phenylalanine (20 mM), glutamine (20 mM), cysteine (20 mM), and proline (20 mM) generated lumen negative currents (I (glc), I (phe), I (gln), I (cys), and I (pro)), respectively, which gradually declined following application of the PI3 kinase inhibitor Wortmannin (1 muM). Within 40 min, Wortmannin treatment significantly decreased I (glc) by 39 +/- 10% (n = 5), I (phe) by 70 +/- 7% (n = 4), I (gln) by 69 +/- 8% (n = 4), I (cys) by 67 +/- 8% (n = 6), and I (prol) by 79 +/- 12% (n = 3). A similar decline of I (glc) was observed following application of the PI3 kinase inhibitor LY294002 (50 microM). Exposure to the inhibitors did not significantly alter transepithelial potential difference and resistance in the absence of substrates for electrogenic transport. The observations suggest that the electrogenic transport of glucose and several amino acids requires the continued activity of PI3 kinase.

Transepithelial flux of early and advanced glycation compounds across Caco-2 cell monolayers and their interaction with intestinal amino acid and peptide transport systems

Maillard products arise from condensation reactions between amino acids or proteins with reducing sugars during food processing. As ubiquitous components of human food, these early or advanced glycation products may be subject to intestinal absorption. The present study was performed to investigate the intestinal uptake of Maillard products and to determine whether they are substrates for peptide and amino acid transporters expressed at the apical membrane of Caco-2 cells. At a concentration of 10 mM, N(epsilon)-(carboxymethyl)-L-lysine, N(alpha)-hippuryl-N(epsilon)-(1-deoxy-D-fructosyl)-L-lysine, N(alpha)-hippuryl-N(epsilon)-(carboxymethyl)-L-lysine and N(epsilon)-(1-deoxy-D-fructosyl)-L-lysine inhibited the [(14)C]glycylsarcosine uptake mediated by the H(+)-peptide co-transporter PEPT1 by 13 to 45%. For N(epsilon)-(1-deoxy-D-fructosyl)-L-lysine, an inhibitory constant of 8.7 mM was determined, reflecting a low affinity to PEPT1 in comparison with natural dipeptides. Uptake of L-[(3)H]lysine was weakly affected by N(epsilon)-(carboxymethyl)-L-lysine, N(alpha)-hippuryl-L-lysine and N(alpha)-hippuryl-N(epsilon)-(carboxymethyl)-L-lysine but strongly inhibited by N(epsilon)-(1-deoxy-D-fructosyl)-L-lysine (81%). None of the Maillard products was able to inhibit the uptake of L-[(3)H]leucine by more than 15%. We also studied the transepithelial flux of Maillard products across Caco-2 cell monolayers cultured on permeable filters. The flux rates of Maillard products ranged from 0.01 to 0.3%/cm(2) per h and were shown to be much lower than those of carrier substrates such as glycylsarcosine, L-proline and the space marker [(14)C]mannitol. We conclude that the Maillard products investigated in the present study are neither transported by PEPT1 nor by carriers for neutral amino acids. The low transepithelial flux measured for these compounds most probably occurs by simple diffusion.

Increased Expression of Specific Intestinal Amino Acid and Peptide Transporter mRNA in Rats Fed by TPN Is Reversed by GLP-2

Intestinal function depends on the presence of luminal nutrients and is altered during starvation and refeeding. Amino acids are essential for enterocytes, but the luminal supply is compromised with changes in dietary intake. To test the hypothesis that during periods of restricted luminal nutrient availability mucosal cells undergo adaptations aimed toward preserving amino acid supply, the expression of amino acid and peptide transporter mRNAs was quantified in rats with no oral intake, whose nutritional status was maintained with total parenteral nutrition (TPN). The role of the intestinotrophic hormone glucagon-like peptide-2 (GLP-2) was investigated in the adaptive responses. Rats were administered TPN with or without exogenous GLP-2. Amino acid and peptide transporter mRNAs in small intestine mucosa were measured by semiquantitative RT-PCR. Compared with orally fed rats, removal of luminal nutrition increased the expression of ASCT1, SAT2, and GLYT1 mRNAs in the duodenum and of ASCT2, EAAC1, NBAT, and PepT1 mRNAs in the ileum. CAT1, PAT1, and SN2 mRNA abundances were unaffected. GLP-2 reversed these effects. Three subgroups of transporters were identified by regional differences in response to TPN. This may reflect differing roles for substrates of transporters located apically and basally and along the proximal-distal axis of the intestine. The importance of maintaining amino acid supply for intestinal mucosal cells is illustrated.

Dietary protein reduction in sheep and goats: different effects on L-alanine and L-leucine transport across the brush-border membrane of jejunal enterocytes.

It was the aim of this study to examine the potential regulatory effects of a long-term low dietary protein supply on the transport capacity of the jejunal brush-border membrane for amino acids. For this purpose, we used the neutral amino acids L-alanine (representative for nonessential amino acids) and L-leucine (representative for essential amino acids) as model substances. Ten sheep lambs, 8 weeks of age and 19-27 kg body weight, were allotted to two dietary regimes with either adequate or reduced protein supply which was achieved by 17.9% and 9.7% of crude protein in the concentrated feed, respectively. The feeding periods were 4-6 weeks in length. Similarly, eight goat kids of 5-7 weeks of age and 8-14 kg body weight were allotted to either adequate (crude protein 20.1%, feeding period 9-12 weeks) or reduced protein supply (10.1%, feeding period 17-18 weeks). Dietary protein reduction in lambs caused a significant body weight loss of 0.6 +/- 0.7 kg, whereas the body weight in control animals increased by 1.9 +/- 0.7 kg (P<0.05). Plasma urea concentrations decreased significantly by 60% (low protein 2.3 +/- 0.1 versus control 5.7 +/- 0.2 mmol l(-1), P<0.001). In kids, reduction of dietary protein intake led to significant decreases of the daily weight gain by 48% from 181 +/- 8 g to 94 +/- 3 g (P<0.001) and daily dry matter intake by 27% from 568 +/- 13 g to 417 +/- 6 g (P<0.01). Respective urea concentrations in plasma were reduced by 77% from 5.2 +/- 0.4 to 1.2 +/- 0.2 mmol l(-1) (P<0.01). Kinetic analyses of the initial rates of alanine uptake into isolated jejunal brush-border membrane vesicles from sheep and goats as affected by low dietary protein supply yielded that the apparent Km was neither significantly different between the species nor significantly affected by the feeding regime thus ranging between 0.12 and 0.16 mmol.l(-1). Reduction of dietary protein, however, resulted in significantly decreased Vmax values of the transport system by 25-30%, irrespective of the species. Kinetic analyses of the initial rates of leucine uptake into jejunal brush-border membrane vesicles from sheep and goats yielded that leucine uptake was mediated by Na+-dependent as well as Na+-independent processes. Similar to alanine, apparent Km values of leucine uptake were neither different between the species nor affected due to low dietary protein and ranged between 0.08 and 0.15 mmol l(-1). In contrast to the alanine transport mechanism, dietary protein reduction resulted in increased Vmax values of Na+-dependent leucine transport by 53% in sheep and 230% in goats. Similarly, Na+-independent leucine uptake was stimulated by 85% and 200% in sheep and in goats, respectively. This study shows adaptation of amino acid absorption at the brush-border membrane level of jejunal enterocytes of small ruminants due to dietary protein reduction. Whereas the transport capacity for the nonessential amino acid alanine was reduced due to low dietary protein, the transport capacity for the essential amino acid leucine was markedly stimulated. From this, the involvement of rather different feedback mechanisms in adaptation of intestinal amino acid transport mechanisms has to be discussed.

Role of specific activators of intestinal amino acid transport in Bombyx mori larval growth and nutrition.

Nutrient absorption and its modulation are critical for animal growth. In this paper, we demonstrate that leucine methyl ester (Leu-OMe) can greatly increase the activity of the transport system responsible for the absorption of most essential amino acids in the larval midgut of the silkworm Bombyx mori. We investigated leucine uptake activation by Leu-OMe in brush border membrane vesicles and in the apical membrane of epithelial cells in the midgut incubated in vitro. Moreover, the addition of this strong activator of amino acid absorption to diet significantly affected larval growth. Silkworms fed on artificial diet supplemented with Leu-OMe reached maximum body weight 12-18 h before control larvae, and produced cocoon shells up to 20% heavier than those of controls. The activation of amino acid absorption plays an essential role in larval development so that larval growth and cocoon production similar to controls reared on an artificial diet with 25% of dry mulberry leaf powder were observed in silkworms fed on an artificial diet with only 5% of mulberry powder. Arch.

Medical and surgical therapy of the cystine stone patient.

Cystinuria is an inherited defect in renal tubular and intestinal transport of dibasic amino acids that results in elevated urinary excretion of cystine, ornithine, lysine, and arginine. The only clinical manifestation of this disease is the development of urinary tract cystine calculi. Cystinuric patients suffer recurrent stone episodes, requiring an aggressive multi-modal approach to management. This article reviews the results of medical prevention regimens, the role of minimally invasive urologic intervention, and the recent insights into the complex genetic basis for the varied cystinuric phenotypes.

Growth factors regulation of rabbit sodium-dependent neutral amino acid transporter ATB0 and oligopeptide transporter 1 mRNAs expression after enteretomy.

Sucessful intestinal adaptation after massive enterectomy is dependent on increased efficiency of nutrient transport. However, midgut resection (MGR) in rabbits induces an initial decrease in sodium-dependent brush border neutral amino acid transport, whereas parenteral epidermal growth factor (EGF) and growth hormone (GH) reverse this downregulation. We investigated intestinal amino acid transporter B0 (ATB0) and oligopeptide transporter 1 (PEPT 1) mRNA expression after resection and in response to EGF and/or GH. Rabbits underwent anesthesia alone (control) or proximal, midgut, and distal resections. Full-thickness intestine was harvested from all groups on postoperative day (POD) 7, and on POD 14 from control and MGR rabbits. A second group of MGR rabbits received EGF and/or GH for 7 days, beginning 7 days after resection. ATB0 and PEPT 1 mRNA levels were determined by Northern blot analysis. In control animals, ileal ATB0 mRNA abundance was three times higher than jejunal mRNA, whereas PEPT 1 mRNA expression was similar. By 7 and 14 days after MGR, jejunal ATB0 mRNA abundance was decreased by 50% vs control jejunum. A 50% decrease in jejunal PEPT 1 message was delayed until 14 days after MGR. Treatment with EGF plus GH did not alter ATB0 mRNA expression but doubled PEPT 1 mRNA in the jejunum. The site of resection, time postresection, and growth factors treatment differentially influence ATB0 and PEPT 1 mRNA expression. Enhanced sodium-dependent brush border neutral amino acid transport with GH plus EGF administration is independent of increased ATB0 mRNA expression in rabbit small intestine after enterectomy.

Intestinal transport of monosaccharides and amino acids during postnatal development of mink.

Intestinal development is typically studied using omnivores. For comparative purposes, we examined an altricial carnivore, the mink (Mustela vison). In mink, intestinal dimensions increase up to 8 wk after birth and then remain constant (length) or decrease (mass) into maturity despite continuing gains in body mass. Rates of glucose and fructose transport decline after birth for intact tissues but increase for brush-border membrane vesicles (BBMV). Rates of absorption for five amino acids that are substrates for the acidic (aspartate), basic (lysine), neutral (leucine and methionine), and imino acid (proline) carriers increase between birth and 24 h for intact tissues before declining, but increase after 2 wk for BBMV. The proportion of BBMV amino acid uptake that is Na(+)-dependent increases during development but for aspartate is nearly 100% at all ages. Tracer uptake by BBMV can be inhibited by 100 mmol/l of unlabeled amino acid, except for lysine. BBMV uptake of the dipeptide glycyl-sarcosine does not differ between ages, is not Na(+) dependent, and is only partially inhibited by 100 mmol/l unlabeled dipeptide. Despite the ability to rapidly and efficiently digest high dietary loads of protein, rates of amino acid and peptide absorption are not markedly higher than those of other mammals.

Altered intestinal transport of amino acids in cirrhotic rats: the effect of insulin-like growth factor-I.

The intestine is an important target organ for insulin-like growth factor-I (IGF-I), an anabolic hormone synthesized in the liver upon growth hormone (GH) stimulation. Levels of IGF-I are reduced in cirrhosis, and altered GH/IGF-I axis may contribute to malnutrition in cirrhotic patients. Our aim was to study Na(+)-dependent jejunal transport of amino acids (L-leucine, L-proline, L-glutamic acid, and L-cysteine) in cirrhotic rats and to analyze the effect of IGF-I on this function. IGF-I or saline was administered for 2 wk to rats with CCl(4)-induced cirrhosis and saline was administered to healthy control rats. Transport of amino acids was assessed in brush-border membrane vesicles (BBMV) using (14)C- or (35)S-labeled amino acids, and the kinetic constants V(max) and K(t) were determined. Na(+)-independent uptake of L-leucine, L-proline, L-glutamic acid, and L-cysteine by BBMV was similar in all groups. Na(+)-dependent uptake of all four amino acids was significantly diminished in cirrhotic rats compared with both controls and IGF-I-treated cirrhotic rats. The latter two groups exhibited similar V(max) and K(t), whereas untreated cirrhotic rats had reduced V(max) and increased K(t) compared with normal controls and IGF-I-treated cirrhotic animals. In conclusion, the transport of all four tested amino acids by BBMV is impaired in cirrhotic rats, and low doses of IGF-I can correct this defect.

Changes in expression of intestinal peptide and amino acid transporters in rats fed by total parenteral nutrition

Changes in expression of intestinal peptide and amino acid transporters in rats fed by total parenteral nutrition

Renal polyamine excretion, tubular amino acid reabsorption and molecular genetics in cystinuria.

Cystinuria is an autosomal recessive disorder of the tubular and intestinal resorption of cystine, ornithine, lysine and arginine leading to nephrolithiasis. Three cystinuria types can be distinguished by the mode of inheritance (true recessive or intermediate) and by the pattern of the intestinal amino acid transport. In the present study phenotypes were assessed by the urinary excretion of amino acids related to creatinine, the percentage tubular amino acid reabsorption and the urinary excretion of polyamines as a possible indicator of the intestinal transport defect. However, our thorough phenotyping did not reveal more than two cystinuria types. Genotypes were examined in linkage analyses and single-strand conformation polymorphism-based mutation identification. The SLC3A1 mutations M467T and T216M were disease causing in our homozygous patients of type I cystinuria. We can show the association of type I cystinuria with SLC3A1 and of non-type I cystinuria with a yet unidentified gene on chromosome 19q13.1. Our phenotype and genotype analyses provide evidence for only two types of cystinuria in the investigated patient cohort.

Gastrointestinal effects of growth hormone.

GH receptor immunoreactivity is found throughout the gastrointestinal tract. GH has proliferative effects upon intestinal epithelium, and influences enteroendocrine cell secretion, calcium absorption, and intestinal amino acid and ion transport. The proliferative effects of GH may be reflected in the increased incidence of neoplastic colonic polyps in individuals with long-term GH excess reported by some investigators. GH also increases hepatic cytochrome P450 expression, potentially altering drug and steroid hormone metabolism. Current clinical research efforts include the use of exogenous GH as a stimulant of gut growth and adaptation in patients who have undergone massive intestinal resection. Exogenous GH is also being studied in animal models of critical illness where it appears to increase intestinal glutamine uptake, which may prevent deterioration of the intestinal mucosal barrier.

Contemporary management of cystinuria.

Cystinuria is an autosomal recessive disorder characterized by a defect in intestinal and renal tubular transport of dibasic amino acids which results in excessive urinary excretion of cystine. Because of the relative insolubility of cystine in urine, patients with this condition are prone to recurrent stone formation. Medical therapy aims both to decrease the urinary concentration of cystine and to increase its solubility. Standard prevention and treatment regimens include hydration, moderate salt and protein restriction, oral alkalinization, and thiol derivatives. Despite aggressive medical management, however, cystinuric patients are likely to suffer frequent recurrent episodes of stones necessitating urologic intervention. Fortunately, the application of safe and efficacious minimally invasive modalities, including advancements in shockwave lithotripsy, ureteroscopic lithotripsy, and percutaneous nephrolithotomy, have obviated open operative intervention in nearly all cases.

Epidermal growth factor regulates fatty acid uptake and metabolism in Caco-2 cells.

Epidermal growth factor (EGF) has been reported to stimulate carbohydrate, amino acid, and electrolyte transport in the small intestine, but its effects on lipid transport are poorly documented. This study aimed to investigate EGF effects on fatty acid uptake and esterification in a human enterocyte cell line (Caco-2). EGF inhibited cell uptake of [14C]palmitate and markedly reduced its incorporation into triglycerides. In contrast, the incorporation in phospholipids was enhanced. To elucidate the mechanisms involved, key steps of lipid synthesis were investigated. The amount of intestinal fatty acid-binding protein (I-FABP), which is thought to be important for fatty acid absorption, and the activity of diacylglycerol acyltransferase (DGAT), an enzyme at the branch point of diacylglycerol utilization, were reduced. EGF effects on DGAT and on palmitate esterification occurred at 2-10 ng/ml, whereas effects on I-FABP and palmitate uptake occurred only at 10 ng/ml. This suggests that EGF inhibited palmitate uptake by reducing the I-FABP level and shifted its utilization from triglycerides to phospholipids by inhibiting DGAT. This increase in phospholipid synthesis might play a role in the restoration of enterocyte absorption function after intestinal mucosa injury.

Identification and Characterization of a Membrane Protein (y+L Amino Acid Transporter-1) That Associates with 4F2hc to Encode the Amino Acid Transport Activity y+L: A CANDIDATE GENE FOR LYSINURIC PROTEIN INTOLERANCE

We have identified a new human cDNA (y+L amino acid transporter-1 (y+LAT-1)) that induces system y+L transport activity with 4F2hc (the surface antigen 4F2 heavy chain) in oocytes. Human y+LAT-1 is a new member of a family of polytopic transmembrane proteins that are homologous to the yeast high affinity methionine permease MUP1. Other members of this family, the Xenopus laevis IU12 and the human KIAA0245 cDNAs, also co-express amino acid transport activity with 4F2hc in oocytes, with characteristics that are compatible with those of systems L and y+L, respectively. y+LAT-1 protein forms a approximately 135-kDa, disulfide bond-dependent heterodimer with 4F2hc in oocytes, which upon reduction results in two protein bands of approximately 85 kDa (i.e. 4F2hc) and approximately 40 kDa (y+LAT-1). Mutation of the human 4F2hc residue cysteine 109 (Cys-109) to serine abolishes the formation of this heterodimer and drastically reduces the co-expressed transport activity. These data suggest that y+LAT-1 and other members of this family are different 4F2 light chain subunits, which associated with 4F2hc, constitute different amino acid transporters. Human y+LAT-1 mRNA is expressed in kidney >> peripheral blood leukocytes >> lung > placenta = spleen > small intestine. The human y+LAT-1 gene localizes at chromosome 14q11.2 (17cR approximately 374 kb from D14S1350), within the lysinuric protein intolerance (LPI) locus (Lauteala, T., Sistonen, P. , Savontaus, M. L., Mykkanen, J., Simell, J., Lukkarinen, M., Simmell, O., and Aula, P. (1997) Am. J. Hum. Genet. 60, 1479-1486). LPI is an inherited autosomal disease characterized by a defective dibasic amino acid transport in kidney, intestine, and other tissues. The pattern of expression of human y+LAT-1, its co-expressed transport activity with 4F2hc, and its chromosomal location within the LPI locus, suggest y+LAT-1 as a candidate gene for LPI.

Comparative Aspects of Chloride-Dependent Amino Acid Transport Across the Brush-Border Membrane of Mammalian Small Intestine

Chloride-dependent amino acid transport has been described in several tissues. This article briefly reviews the evidence of cotransport of chloride and amino acids across the brush-border membrane of rabbit distal ileum. On the basis of amino acid carriers described in the rabbit and the surveys of chloride-dependence reported, a comparison of amino acid carriers in the mammalian small intestine is performed. Additional characteristics of the carriers in the different species are included in the discussion when necessary. From this comparison the rabbit distal ileum and the pig small intestine emerge as the best models of amino acid transport in the human small intestine.