Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acid-base homeostasis depends on glutamine flow from producer organs to those capable of generating bicarbonate. Glutamine oxidation, the prerequisite metabolic transformation, can be expressed by many sites; however, net base generation requires that glutamine flow be directed to a specific organ, the kidney. Normally, glutamine flows from the periphery to the splanchnic bed, providing a major fuel and supporting ureagenesis. Glutamine flow in chronic metabolic acidosis, on the other hand, is rerouted to the kidneys; asymmetrical distribution of NH+4 and HCO3- into the urine and renal vein subserves restoration of alkaline reserves. Clearly, glutamine flows in accordance with physiological demands, yet little is known of the regulatory mechanisms. As a model, chronic metabolic acidosis alters two aspects of this vital flow, its direction and magnitude. Characteristically the direction of flow is away from the splanchnic bed and into the kidneys associated with a marked fall in arterial glutamine concentration, restoring arterial level returns flow to the splanchnic bed sink. Thus glutamine homeostasis is sacrificed to impart direction to interorgan glutamine flow. Although multiple sites contribute to glutamine homeostasis, of great strategic importance is the potent hepatic glutaminase flux activated by portal venous NH+4 fed forward by gut metabolism; local hydrogen ion concentration modulates the effectiveness of this activator. Acute regulation of flow direction can be exerted by the lungs in determining the prevailing pCO2 and cellular acidity; respiratory compensation in chronic acidosis allows the expression of hepatic glutaminase, thereby suppressing arterial glutamine concentration. The enormous magnitude of glutamine flowing from muscle to the kidneys is supported by adaptive increases in glutamine synthetase and mitochondrial glutaminase, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interorgan glutamine flow in metabolic acidosis. 332 41

The glutamine/amino acid transporter was solubilized from rat renal apical plasma membrane (brush-border membrane) with C12E8 and reconstituted into liposomes by removing the detergent from mixed micelles by hydrophobic chromatography on Amberlite XAD-4. The reconstitution was optimised with respect to the protein concentration, the detergent/phospholipid ratio and the number of passages through a single Amberlite column. The reconstituted glutamine/amino acid transporter catalysed a first-order antiport reaction stimulated by external, not internal, Na+. Optimal activity was found at pH 7.0. The sulfhydryl reagents HgCl2, mersalyl and p-hydroxymercuribenzoate and the amino acids alanine, serine, threonine, cysteine, asparagine, methionine and valine strongly inhibited the transport, whereas the amino acid analogue methylaminoisobutyrate had no effect. Glutamine, alanine, serine, asparagine, threonine were efficiently translocated from outside to inside and from inside to outside the proteoliposomes as well. Cysteine and valine were translocated preferentially from outside to inside. The Km for glutamine on the external and internal side of the transporter was 0.47 and 11 mM, respectively; the values were not influenced by the type of the counter substrate. The transporter is functionally asymmetrical and it is unidirectionally inserted into the proteoliposomal membrane with an orientation corresponding to that of the native membrane. By a bisubstrate kinetic analysis of the glutamine antiport, a random simultaneous mechanism was found. The glutamine antiport was strongly stimulated by internal nucleoside triphosphates and, to a lower extent, by pyrophoshate. The reconstituted glutamine/amino acid transporter functionally corresponds to the ASCT2 protein.
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PMID:Reconstitution into liposomes of the glutamine/amino acid transporter from renal cell plasma membrane: functional characterization, kinetics and activation by nucleotides. 1558 47