The study provides biochemical evidence for two distinct types of myosin-active sites that differ in their rates of intermediate oxygen exchange during ATP hydrolysis.
Does not alter clinical practice; hypothesis-generating for myosin heterogeneity in cardiac energetics research.
During the hydrolysis of MgAW by myosin or its active subfragments, there is an exchange of oxygen between water and the terminal phosphate group of enzyme-bound nucleotide.Ultimately this appears in the Pi released from the enzyme.An analysis of the lROlabeled species from hydrolysis of [Y-'~O]ATP by actinactivated tryptic heavy meromyosin (HMM), between 3 and 17 s of turnover time (set by the concentration of actin), showed a substantial fraction of Pi, about 306, that had undergone no exchange; the other 70% or so included a large fraction of completely exchanged Pi, about 50% of the total, and smaller fractions of partially exchanged species, to give an average exchange of 70 to 75% in the Pi pool.The results indicate two kinds of myosin-active site; one that exchanges all four phosphate oxygens rapidIy and produces about 70% of the Pi (the fast exchanger) and another that exchanges very slowly, if at all (the slow or nonexchanger), and produces the rest of the Pi.Both kinds of site appear to have about the same affinity for actin and about the same V,, for actin-activated hydrolysis.The similar distribution pattern for HMM and myosin at comparable turnover times appears to rule out schemes for the production of nonexchanged Pi that depend primarily on complex kinetics of interfilament interaction bet ween myosin and actin.In contrast to purified tryptic HMM or myosin, a number of other fragments of myosin show little if any slow exchange.Apparently, in such preparations, some proteolytic modification brings the rate of exchange by the normally SIOW exchanger up to a level comparable with that of the fast exchanger.There appears to be some correlation between this effect of proteolysis and damage to the 5,5'-dithiobis(Z-nitrobenzoic acid) light chain.The two myosin-active sites that we postulate could represent two different kinds of myosin molecule or two different heads on each molecule.If there are two different heads per molecule, the exchange studies may
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Shukla et al. (1980) studied this question.
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