Characterization of dimethylguanosine, phenylethylamine, and phenylacetic acid as inhibitors of Ca2+ ATPase in end-stage renal failure.

doi:10.1681/ASN.V971249

Paper

Characterization of dimethylguanosine, phenylethylamine, and phenylacetic acid as inhibitors of Ca2+ ATPase in end-stage renal failure.

Published Jul 1, 1998 · J. Jankowski, H. Luftmann, Martin Tepel

Journal of the American Society of Nephrology : JASN

Q1 SJR score

23

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0

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Abstract

The activity of the plasma membrane Ca2+ ATPase of chronic renal failure patients is decreased by circulating inhibitors yet to be characterized. In this study, inhibitors of Ca2+ ATPase were isolated from ultrafiltrate of patients with end-stage renal failure. They were identified as dimethylguanosine, phenylethylamine, and phenylacetic acid by chromatography and mass spectrometry. Ca2+ ATPase activity was measured spectrophotometrically as the difference in hydrolysis of ATP in the presence and absence of Ca2+ with different concentrations of ATP and the isolated substances. All of the identified compounds are sufficiently lipophilic to penetrate the blood-brain barrier and to accumulate in cerebral tissue. The inhibitory effects of these agents were additive. The apparent K(m) values for ATP and Ca2+ were not altered by these substances, suggesting a noncompetitive mechanism of inhibition. In plasma of healthy subjects, the substances were not detectable. The Ca2+ ATPase inhibitors identified may play a role in the pathophysiology of end-stage renal failure and, potentially, in monitoring toxic effects on cellular Ca2+ metabolism in renal failure.

In Vitro Study

Study Snapshot

Dimethylguanosine, phenylethylamine, and phenylacetic acid are additive inhibitors of Ca2+ ATPase in end-stage renal failure patients, potentially playing a role in the pathophysiology and monitoring toxic effects on cellular Ca2+ metabolism.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Characterization of dimethylguanosine, phenylethylamine, and phenylacetic acid as inhibitors of Ca2+ ATPase in end-stage renal failure.

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References

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Citations

Metabolomics to Identify Unclassified Uremic Toxins: A Comprehensive Literature Review

Untargeted metabolomics provides a more balanced view of uremic retention than targeted approaches, with higher chances of revealing beneficial potential of some metabolites.

Reduced uremic metabolites are prominent feature of sarcopenia, distinct from antioxidative markers for frailty

Sarcopenia markers show a close link between muscle and kidney function, while frailty markers indicate a vulnerable state to oxidative stress.

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Intracellular calcium levels play a crucial role in breast cancer progression, and disrupting this balance may lead to tumor progression and potential targets for cancer treatment.

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Phenylacetic acid has a single high-affinity binding site on human serum albumin, acting as a carrier protein for this uremic toxin.

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Adsorption combined with dialysis membranes effectively increases the removal rate of protein-bound, hydrophobic uremic toxins in CKD-5D patients, potentially improving their health outcomes.