Amino Acid Transport Across the Mammalian Intestine

Abstract

The small intestine mediates the absorption of amino acids after ingestion of protein and sustains the supply of amino acids to all tissues. The small intestine is an important contributor to plasma amino acid homeostasis, while amino acid transport in the large intestine is more relevant for bacterial metabolites and fluid secretion. A number of rare inherited disorders have contributed to the identification of amino acid transporters in epithelial cells of the small intestine, in particular cystinuria, lysinuric protein intolerance, Hartnup disorder, iminoglycinuria, and dicarboxylic aminoaciduria. These are most readily detected by analysis of urine amino acids, but typically also affect intestinal transport. The genes underlying these disorders have all been identified. The remaining transporters were identified through molecular cloning techniques to the extent that a comprehensive portrait of functional cooperation among transporters of intestinal epithelial cells is now available for both the basolateral and apical membranes. Mouse models of most intestinal transporters illustrate their contribution to amino acid homeostasis and systemic physiology. Intestinal amino acid transport activities can vary between species, but these can now be explained as differences of amino acid transporter distribution along the intestine. © 2019 American Physiological Society. Compr Physiol 9:343‐373, 2019.

Functional analysis of OCTN2 and ATB0,+ in normal human airway epithelial cells

“…As far as ATB 0,+ is concerned, data of transport analysis are fully in agreement with the immunocytochemical staining which showed a strong positivity of the protein at plasma membrane at the apical side. As far as the biologiocal role of this transporteer, it has been suggested that ATB 0,+ is expressed at places where the body interfaces with microbes, such as lung and colon and it may be involved in reducing available nutrients to bacteria [14]. Accordingly, the transporter is upregulated in inflammatory states, such as ulcerative colitis, Crohn's disease and colon cancer [14].…”

“…As far as the biologiocal role of this transporteer, it has been suggested that ATB 0,+ is expressed at places where the body interfaces with microbes, such as lung and colon and it may be involved in reducing available nutrients to bacteria [14]. Accordingly, the transporter is upregulated in inflammatory states, such as ulcerative colitis, Crohn's disease and colon cancer [14]. Moreover, genome-wide association studies has been recently identified ATB 0,+ (SLC6A14) as a genetic modifier of lung disease severity in cystic fibrosis, providing a mechanism by which it regulates Pseudomonas aeruginosa attachment to human bronchial epithelial cells [24].…”

“…This transporter has a low affinity (Km = 800 μM) for L-carnitine, but an high concentrative capacity, being energized by the transmembrane gradients of Na + and Cl − , as well as by membrane potential [12]. Consistent with functional studies, ATB 0,+ is expressed in the lung and intestine under normal conditions [13,14] where it is supposed to be mainly involved in nutrient uptake, due to its broad specificity and concentrative transport mechanisms [15,16].…”

y+LAT1 and y+LAT2 contribution to arginine uptake in different human cell models: Implications in the pathophysiology of Lysinuric Protein Intolerance

“…As reported by Broer, both renal and intestinal LPI phenotypes are explained by the presence of the sole system y+L transporter in the basolateral membranes of these tissues ; indeed, the lack of a functional y+LAT1 consequent to SLC7A7 mutations is realistically the reason for the impaired absorption‐reabsorption of cationic amino acids, and, in turn, for the low plasma levels of arginine and other cationic amino acids in LPI patients. Our study of arginine transcellular fluxes in polarized layers of Caco‐2 cells confirms that system y + L in this model is operative at the basolateral side, blowing out arginine in exchange with leucine plus sodium.…”

Phenylpropionc acid produced by gut microbiota alleviates acetaminophen-induced hepatotoxicity

“…Therefore, the amount of PPA produced by gut bacterial metabolism of phenylalanine will be dependent on total numbers of gut bacteria harboring the reductive pathway genes and the availability of the substrate phenylalanine. Free phenylalanine in diet is absorbed mostly in the small intestine (59), and only a small fraction reaches the lower gastrointestinal tract. A large portion of phenylalanine available to gut bacteria in the large intestine is derived from proteolytic degradation of proteins by gut bacteria, which releases free phenylalanine or phenylalanine-containing peptides (60).…”