Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Among the toxins accumulating in the circulation of patients with fulminant hepatic failure (FHF) are substances which inhibit leucocyte ouabain-sensitive sodium transport. A similar inhibition of brain Na+,K+-ATPase could lead to both coma and cerebral edema found in these patients which are associated with high mortality. In this study, we have investigated the effect of sera from FHF on normal rat brain Na+,K+-ATPase activity in vitro. Serum from patients with FHF significantly decreased the ouabain-sensitive Na+,K+-ATPase activity (13.58 +/- S.D. 2.60 mumoles Pi mg protein-1 hr-1) in the rat brain membrane preparation in vitro as compared to normal serum (20.33 +/- 3.24 mumoles Pi mg protein-1 hr-1, p less than 0.001). A final serum dilution of 1 in 40 was required to abolish the inhibition of Na+,K+-ATPase activity. Cerebrospinal fluid obtained at postmortem from FHF patients also contained the inhibitory substances. Serum from patients in coma due to decompensated chronic liver disease inhibited the Na+,K+-ATPase activity (17.25 +/- 1.37 mumoles Pi mg protein-1 hr-1), but this was less marked than with FHF serum. Hence, the inhibition of brain Na+,K+-ATPase by substances accumulating in the serum in FHF may be important in the pathogenesis of hepatic coma.
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PMID:Inhibition of rat brain Na+,K+-ATPase activity by serum from patients with fulminant hepatic failure. 631 61

Methanethiol (CH3SH) has been implicated in the pathogenesis of hepatic coma. Studies are presented to identify the possible biochemical basis of anesthesia-like effects of methanethiol and those features which distinguish such effects from common anesthetics and may represent the basis of its toxicity. CH3SH was found to stabilize erythrocyte membranes against hypotonic hemolysis at relatively low concentrations. At 37 degrees C the AH25 value for human erythrocyte antihemolysis was observed at a concentration of 0.34 mumol of CH3SH bound per mg of erythrocyte protein. Similar results were obtained with rat erythrocytes. This property of CH3SH is in common with other anesthetic agents. Anesthetic agents also inhibit the membrane-associated Na+,K+-adenosine triphosphatase (ATPase); however, for effective and nontoxic agents of this type the inhibition of ATPase activity is elicited at concentrations which are at least an order of magnitude higher than those which influence the membrane stability characterized by the antihemolysis effect (P. Seeman, Pharmacol. Rev. 24: 583-655, 1972). CH3SH was also found to inhibit the membrane Na+,K+-ATPase activity. The I25 value for the inhibition of human erythrocyte ATPase activity was obtained at CH3SH concentration of 0.12 mM which corresponded to 0.3 mumol of CH3SH bound per mg of erythrocyte membrane protein. Rat erythrocyte membrane ATPase was somewhat more sensitive to CH3SH. In all cases the binding of CH3SH to erythrocytes occurred primarily on the membrane. These results indicate that no differential exists with respect to the dose-response of these two activities associated with human erythrocyte membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of methanethiol on erythrocyte membrane stabilization and on Na+,K+-adenosine triphosphatase: relevance to hepatic coma. 631 65