Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Magnesium is an essential cation, involved in many enzymatic reactions, as a cofactor to adenosine triphosphatases. It is critical in energy-requiring metabolic processes, as well as protein synthesis and anaerobic phosphorylation. Serum Mg concentration is maintained within a narrow range by the kidney and small intestine since under conditions of Mg deprivation both organs increase their fractional absorption of Mg. If Mg depletion continues, the bone store contributes by exchanging part of its content with extracellular fluid (ECF). The serum Mg can be normal in the presence of intracellular Mg depletion, and the occurrence of a low level usually indicates significant Mg deficiency. Hypomagnesemia is frequently encountered in hospitalized patients and is seen most often in patients admitted to intensive care units. The detection of Mg deficiency can be increased by measuring Mg concentration in the urine or using the parenteral Mg load test. Hypomagnesemia may arise from various disorders of the gastrointestinal tract, conditions affecting Mg renal handling, or cellular redistribution of Mg. The gastrointestinal causes include the following: protein-calorie malnutrition, the intravenous administration of Mg-free fluids and total parenteral nutrition, chronic watery diarrhea and steatorrhea, short bowel syndrome, bowel fistula, continuous nasogastric suctioning, and, rarely, primary familial Mg malabsorption. The renal causes include Bartter's and Gitelman's syndrome, post obstructive diuresis, post acute tubular necrosis, renal transplantation, and interstitial nephropathy. Many therapeutic agents cause renal Mg wasting and subsequent deficiency. These include loop and thiazide diuretics, aminoglycosides, cisplatin, pentamidine, and foscarnet. Magnesium deficiency is seen frequently in alcoholics and diabetic patients, in whom a combination of factors contributes to its pathogenesis. Hypomagnesemia is known to produce a wide variety of clinical presentations, including neuromuscular irritability, cardiac arrhythmias, and increased sensitivity to digoxin. Refractory hypokalemia and hypocalcemia can be caused by concomitant hypomagnesemia and can be corrected with Mg therapy. The dose and route of administration of Mg in the treatment of hypomagnesemia is dictated by the clinical presentation, the degree of Mg deficiency, and the renal function.
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PMID:Magnesium deficiency: pathophysiologic and clinical overview. 777 97

Hyperprostaglandin E syndrome/antenatal Bartter syndrome is characterized by NaCl wasting and volume depletion, juxtaglomerula hypertrophy, hyperreninism and secondary hyperaldosteronism. Primary causes are mutations in the gene for Na-K-2Cl-cotransporter, NKCC2, or for potassium channel, ROMK, responsible for medullary NaCl malabsorption. Most intriguing aspect of the syndrome is the association with a massively increased renal prostaglandin production which contributes substantially to the clinical picture of the patients. Therefore the term hyperprostaglandin E syndrome has been introduced. It is unclear how prostaglandins aggravate the NaCl transport deficiency. Aspects to prostaglandin synthesis and receptor-mediated function within the kidney in patients suffering from hyperprostaglandin E syndrome/antenatal Bartter syndrome will be discussed.
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PMID:The role of cyclooxygenases and prostanoid receptorsin furosemide-like salt losing tubulopathy: the hyperprostaglandin E syndrome. 1528 66

Sodium-coupled transporters are ubiquitous pumps that harness pre-existing sodium gradients to catalyse the thermodynamically unfavourable uptake of essential nutrients, neurotransmitters and inorganic ions across the lipid bilayer. Dysfunction of these integral membrane proteins has been implicated in glucose/galactose malabsorption, congenital hypothyroidism, Bartter's syndrome, epilepsy, depression, autism and obsessive-compulsive disorder. Sodium-coupled transporters are blocked by a number of therapeutically important compounds, including diuretics, anticonvulsants and antidepressants, many of which have also become indispensable tools in biochemical experiments designed to probe antagonist binding sites and to elucidate transport mechanisms. Steady-state kinetic data have revealed that both competitive and noncompetitive modes of inhibition exist. Antagonist dissociation experiments on the serotonin transporter (SERT) have also unveiled the existence of a low-affinity allosteric site that slows the dissociation of inhibitors from a separate high-affinity site. Despite these strides, atomic-level insights into inhibitor action have remained elusive. Here we screen a panel of molecules for their ability to inhibit LeuT, a prokaryotic homologue of mammalian neurotransmitter sodium symporters, and show that the tricyclic antidepressant (TCA) clomipramine noncompetitively inhibits substrate uptake. Cocrystal structures show that clomipramine, along with two other TCAs, binds in an extracellular-facing vestibule about 11 A above the substrate and two sodium ions, apparently stabilizing the extracellular gate in a closed conformation. Off-rate assays establish that clomipramine reduces the rate at which leucine dissociates from LeuT and reinforce our contention that this TCA inhibits LeuT by slowing substrate release. Our results represent a molecular view into noncompetitive inhibition of a sodium-coupled transporter and define principles for the rational design of new inhibitors.
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PMID:Antidepressant binding site in a bacterial homologue of neurotransmitter transporters. 1768 33