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. 1998 May;74(5):2658–2665. doi: 10.1016/S0006-3495(98)77971-8

Time-dependent effects of trimethylamine-N-oxide/urea on lactate dehydrogenase activity: an unexplored dimension of the adaptation paradigm.

I Baskakov 1, D W Bolen 1
PMCID: PMC1299605  PMID: 9591689

Abstract

Given that enzymes in urea-rich cells are believed to be just as sensitive to urea effects as enzymes in non-urea-rich cells, it is argued that time-dependent inactivation of enzymes by urea could become a factor of overriding importance in the biology of urea-rich cells. Time-independent parameters (e.g. Tm, k(cat), and Km) involving protein stability and enzyme function have generally been the focus of inquiries into the efficacy of naturally occurring osmolytes like trimethylamine-N-oxide (TMAO), to offset the deleterious effects of urea on the intracellular proteins in the urea-rich cells of elasmobranchs. However, using urea concentrations found in urea-rich cells of elasmobranches, we have found time-dependent effects on lactate dehydrogenase activity which indicate that TMAO plays the important biological role of slowing urea-induced dissociation of multimeric intracellular proteins. TMAO greatly diminishes the rate of lactate dehydrogenase dissociation and affords significant protection of the enzyme against urea-induced time-dependent inactivation. The effects of TMAO on enzyme inactivation by urea adds a temporal dimension that is an important part of the biology of the adaptation paradigm.

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Selected References

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