Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
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Target Concepts:
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Query: UMLS:C0235394 (
wasting
)
8,040
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
A proximal renal tubular acidosis (RTA) is the mechanism underlying the systemic acidosis found in vitamin D deficiency rickets. Acidotic subjects have high levels of PTH. In non-acidotic subjects proximal bicarbonate
wasting
can be induced by exogenous PTH injection.
Carbonic anhydrase
activity is not involved in this process. Calcium infusion is able to suppress both the spontaneous and the PTH-induced bicarbonate leak. The development of RTA in vitamin D deficiency is related to a particular equilibrium between two antagonizing factors at tubular level, parathyroid hormone and calcium.
...
PMID:Proximal renal tubular acidosis in vitamin D deficiency rickets. 81 Jan 89
Genetic disorders of excessive salt loss from sweat glands have been observed in pseudohypoaldosteronism type I (PHA) and cystic fibrosis that result from mutations in genes encoding epithelial Na+ channel (ENaC) subunits and the transmembrane conductance regulator (CFTR), respectively. We identified a novel autosomal recessive form of isolated salt
wasting
in sweat, which leads to severe infantile hyponatremic dehydration. Three affected individuals from a small Bedouin clan presented with failure to thrive, hyponatremic dehydration and hyperkalemia with isolated sweat salt
wasting
. Using positional cloning, we identified the association of a Glu143Lys mutation in carbonic anhydrase 12 (CA12) with the disease.
Carbonic anhydrase
is a zinc metalloenzyme that catalyzes the reversible hydration of carbon dioxide to form a bicarbonate anion and a proton. Glu143 in CA12 is essential for zinc coordination in this metalloenzyme and lowering of the protein-metal affinity reduces its catalytic activity. This is the first presentation of an isolated loss of salt from sweat gland mimicking PHA, associated with a mutation in the CA12 gene not previously implicated in human disorders. Our data demonstrate the importance of bicarbonate anion and proton production on salt concentration in sweat and its significance for sodium homeostasis.
...
PMID:Autosomal recessive hyponatremia due to isolated salt wasting in sweat associated with a mutation in the active site of Carbonic Anhydrase 12. 2118 99
Carbonic anhydrase
(CAII) binds to the electrogenic basolateral Na
+
-[Formula: see text] cotransporter (NBCe1) and facilitates [Formula: see text] reabsorption across the proximal tubule. However, whether the inhibition of CAII with acetazolamide (ACTZ) alters NBCe1 activity and interferes with the ammoniagenesis pathway remains elusive. To address this issue, we compared the renal adaptation of rats treated with ACTZ to NH
4
Cl loading for up to 2 wk. The results indicated that ACTZ-treated rats exhibited a sustained metabolic acidosis for up to 2 wk, whereas in NH
4
Cl-loaded rats, metabolic acidosis was corrected within 2 wk of treatment. [Formula: see text] excretion increased by 10-fold in NH
4
Cl-loaded rats but only slightly (1.7-fold) in ACTZ-treated rats during the first week despite a similar degree of acidosis. Immunoblot experiments showed that the protein abundance of glutaminase (4-fold), glutamate dehydrogenase (6-fold), and SN1 (8-fold) increased significantly in NH
4
Cl-loaded rats but remained unchanged in ACTZ-treated rats. Na
+
/H
+
exchanger 3 and NBCe1 proteins were upregulated in response to NH
4
Cl loading but not ACTZ treatment and were rather sharply downregulated after 2 wk of ACTZ treatment. ACTZ causes renal [Formula: see text]
wasting
and induces metabolic acidosis but inhibits the upregulation of glutamine transporter and ammoniagenic enzymes and thus suppresses ammonia synthesis and secretion in the proximal tubule, which prevented the correction of acidosis. This effect is likely mediated through the inhibition of the CA-NBCe1 metabolon complex, which results in cell alkalinization. During chronic ACTZ treatment, the downregulation of both NBCe1 and Na
+
/H
+
exchanger 3, along with the inhibition of ammoniagenesis and [Formula: see text] generation, contributes to the maintenance of metabolic acidosis.
...
PMID:Acetazolamide causes renal [Formula: see text] wasting but inhibits ammoniagenesis and prevents the correction of metabolic acidosis by the kidney. 3265 59
