title: Time-dependent effects of trimethylamine-N-oxide/urea on lactate dehydrogenase activity: an unexplored dimension of the adaptation paradigm.
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.
authors.affiliation: Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston 77555-1052, USA.
authors.forename: I
authors.initials: I
authors.lastname: Baskakov
authors.forename: D W
authors.initials: DW
authors.lastname: Bolen
mesh_terms: D000818:Animals; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D046911:Macromolecular Substances; D008744:Methylamines / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000201:enzymology; D016877:Oxidants / Q000494:pharmacology; D011817:Rabbits; D013997:Time Factors; D014508:Urea / Q000494:pharmacology*
chemical_list: D046911:Macromolecular Substances; D008744:Methylamines; D016877:Oxidants; D014508:Urea; D007770:L-Lactate Dehydrogenase; C005855:trimethyloxamine