Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020438 (hypercalciuria)
 2,502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Advances in the understanding of amino acid metabolism and of the interaction of amino acids with skeletal muscle, liver, brain, and other tissues have led to refinements of parenteral amino acid solutions. Clinical situations may dictate the use of specific amino acid formulations. Branched-chain amino acid (BCAA) solutions may normalize aberrant amino acid profiles in patients with hepatic encephalopathy; however, controlled trials demonstrate little effect on clinical outcome, and the effectiveness in patients with acute liver failure or undergoing orthotopic liver transplantation is unproved. BCAA solutions have also been tried in septic and severely stressed patients with equivocal results. Renal failure has been treated with essential amino acid solutions, yet low-dose standard amino acid formulations are probably equally effective. Pediatric preparations have been tailored to "normalize" amino acid profiles to those of healthy term, breast-fed neonates. Recent studies suggest that premature infants receiving these formulations may achieve intrauterine growth rates, although the effect on long-term outcome is unknown. Glutamine may be essential for the preservation of intestinal mucosal structure and function; further study is indicated to determine the necessity of adding glutamine to parenteral amino acid solutions. Recently, amino acid infusions have been associated with enhanced ventilatory drive, possibly via stimulation of central ventilatory mechanisms. A variety of other side effects have been documented, including acidosis, hyperammonemia, hypercalciuria, and possibly bone disease and hepatotoxicity. Further understanding of the metabolism of intravenous infusion of amino acids is necessary to provide optimal nutritional protein support. Because full information regarding the complex effects of intravenous substrates is lacking, special amino acid formulations must be used with caution.
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PMID:General and specialized parenteral amino acid formulations for nutrition support. 210 46

The transient receptor potential channel TRPV5 is localized to the apical membrane of the distal renal tubule and plays an important role in the regulation of transepithelial Ca(2+) reabsorption in kidney. We have previously reported that extracellular protons inhibit TRPV5 by binding to glutamate-522 (E522) in the extracellular domain of the channel. We suggested that E522 is an extracellular "pH sensor" and its titration by extracellular protons inhibits TRPV5 via conformational change(s) of the pore helix. We now report that mutation of a pore helix residue glutamate-535 to glutamine (E535Q) enhances the sensitivity of the channel to inhibition by extracellular protons (i.e., shifting the apparent pKa for inhibition by extracellular protons to the more alkaline extracellular pH). The enhancement of extracellular proton-mediated inhibition of E535Q mutant is also dependent on E522. We have also reported that intracellular acidification enhances the sensitivity of TRPV5 to inhibition by extracellular protons. We now find that modulation of the extracellular proton-mediated inhibition by intracellular acidification is preserved in the E535Q mutant. These results provide further support for the idea that pore helix is involved in the regulation of TRPV5 by extracellular protons. Inhibition of TRPV5 by extracellular protons may contribute to hypercalciuria in diseases associated with high acid load.
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PMID:On the role of pore helix in regulation of TRPV5 by extracellular protons. 1733 36