Disorders of Intestinal Transport of Amino Acids

Amino Acid Transport Across Mammalian Intestinal and Renal Epithelia

“…As a result, it appears that in the renal tubule additional transport systems for neutral amino acids exist, most notably for proline and glycine. It has been suggested that the lack of intestinal tryptophan transport is responsible for most if not all clinical phenotypes of Hartnup disorder (375). This is supported by the observation that clinical symptoms are mainly observed in individuals with lower than normal plasma amino acid concentrations (323).…”

“…Bacterial degradation products of methionine, such as ␣-hydroxybutyrate, were found in the urine. A low-methionine diet reduced the symptoms, whereas oral methionine loading caused diar- (375). This suggests that a similar system might be operating in the kidney, but that it is only visible at increased plasma levels of methionine.…”

“…Although amino acid transport has been studied in many types of epithelial cells, this review focuses on mammalian kidney and intestine, because the knowledge is much more advanced in these two tissues. Excellent reviews have covered the nonmolecular aspects of this field (209,224,233,305,315,320,339,343,356,375,418,419). More recently, certain molecular aspects of epithelial transport have been presented (75, 97, 98, 113, 254, 256 -261, 393-396, 398).…”

“…With the exception of histidine, glycine, and taurine, the clearance rate of all amino acids in humans is Ͻ1 ml⅐min Ϫ1 ⅐1.73 m Ϫ2 , in contrast to a value of ϳ120 ml⅐min Ϫ1 ⅐1.73 m Ϫ2 for substances that are neither reabsorbed nor secreted. Based on functional studies in kidney and intestine and the amino acid profile in the urine of individuals with different aminoacidurias, five transport activities were proposed (209,320,375,418): 1) the "neutral system" or "methionine preferring system" transporting all neutral amino acids; 2) the "basic system" transporting cationic amino acids together with cystine; 3) the "acidic system" transporting glutamate and aspartate; 4) the "iminoglycine system" transporting proline, hydroxyproline, and glycine; and 5) the ␤-amino acid system. This review adopts this classification and will discuss each group of amino acids, summarizing the inherited disorders associated with them, functional studies, and the molecular mediators involved in their transport.…”

“…In other pedigrees, glycinuria is observed in heterozygotes (318). Additionally, impaired intestinal transport is observed in some pedigrees (375) but not in others (67). As a result, a total of three mutant alleles have been proposed (67).…”