Kinetic analysis of platelet monoamine oxidase in chronic schizophrenia.
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Adult↗
Biomedical subjects
A Breier
Publications and source records attributed to A Breier.
Is cysteine residue important in FITC-sensitive ATP-binding site of P-type ATPases? A commentary to the state of the art.
Treatment of P-type ATPases (from mammalian sources) by fluorescein isothiocyanate (ITC) revealed the ITC label on a lysine residue that was than considered as essential for binding of ATP in the ATP-binding site of these enzymes. On the other hand, experiments with site directed mutagenesis excluded the presence of an essential Iysine residue that would be localized in the ATP binding sites of ATPases. Other previous studies, including those of ourselves, indicated that the primary site of isothiocyanate interaction may be the sulfhydryl group of a cysteine residue and this may be essential for binding of ATP. In addition considerable knowledge accumulated since yet also about the differences in stability of reaction product of isothiocyanates with SH- or NH2- groups. Based upon evaluation of the data available up to now, in present paper the following tentative roles for lysine and cysteine residues located in the ATP-binding site of P-type ATPases are proposed: The positively charged micro-domain of the lysine residue may probably attract the negatively charged phosphate moiety of the ATP molecule whereas the cysteine residue may probably be responsible for recognition and binding of ATP by creation of a proton bridge with the amino group in position 6 on the adenosine ring of ATP.
Adenosine Triphosphatases↗
Prevention by 7-oxo-prostacyclin of the calcium paradox in rat heart: role of the sarcolemmal (Na,K)-ATPase.
It is demonstrated a fast and significant depression in the sarcolemmal (Na,K)-ATPase activity that occurs as early as 25 sec after the onset of Ca2+ depletion, and participates in the development of Ca(2+)-paradox in the rat heart. Pretreatment of the animals with 7-oxo-prostacyclin (PGI2) 24-48 h prior to the experiment prevented fairly the Ca(2+)-depletion-induced depression in (Na,K)ATPase activity and the accompanying structural and functional damage to the heart and sarcolemma during Ca(2+)-depletion as well as the development of Ca(2+)-paradox during the subsequent Ca(2+)-repletion. Pretreatment with PGI2 was chosen intentionally because previous experiments revealed, that in its late effect the drug is acting via stabilizing the membranes due induction of high activity of (Na,K)-ATPase that has increased affinity to ATP. From results obtained the following may be concluded: If during the phase of Ca(2+)-deprivation, the capability of heart sarcolemma to maintain sodium extrusion remains preserved, the expected aggravation of Ca(2+)-overload injury to Ca(2+)-paradox that would develop during Ca(2+)-repletion, may be definitely prevented. Sufficiently preserved (Na,K)-ATPase activity, hand in hand with stabilized sarcolemmal structure, may prevent an accumulation of sodium beneath the sarcolemma and consequently also an overexcessive entry of Ca2+ into the myocytes.
Animals↗
Adaptation of the heart to ischemia by preconditioning: effects on energy equilibrium, properties of sarcolemmal ATPases and release of cardioprotective proteins.
Ischemic preconditioning of the heart is referred as a manifest increase in tolerance of the myocardium to otherwise damaging ischemic insult, achieved by one or few consequent initial short exposures to ischemia, each followed by reperfusion of the ischemic area. Several mechanisms such as opening of collateral vessels, the action of catecholamines, inositol phosphates, G-proteins and/or adenosine; inhibition of mitochondrial ATPase, the effects of different endogenous protective substances like heat stress or shock proteins, etc., are believed to cooperate in the mechanism of induction of preconditioning or in maintaining its effect. The present study is an attempt to extend the present knowledge about preconditioning from two aspects: i.) the peculiarities of energy equilibrium in preconditioned myocardium including adaptation of cardiac sarcolemmal ATPases to ischemia and/or hypoxia, and ii) participation of a new endogenous cardioprotective substance in the mechanism of preconditioning. The energy equilibrium in preconditioning is characterized by adaptation of cardiac energy demands to the capacity of energy production and delivery decreased by anaerobiosis and is manifested by constant ratios between ATP, ADP, AMP and the sum of ADN. Principles are proposed that may enable a prediction and mathematical modelling of the balanced energetic state in the preconditioned myocardium. These principles are based on thermodynamics and involve besides others a more economic handling of ATP by sarcolemmal ATPases. The latter enzymes adapt themselves to lowered availability of ATP by decreasing besides their Vmax also their values of Km (increase in the affinity) for ATP and some of them even adjust their activation energy (the anaerobiosis-induced elevation of Ea.t. is missing).(ABSTRACT TRUNCATED AT 250 WORDS)
Adaptation, Physiological↗
Inhibition of (Na/K)-ATPase by electrophilic substances: functional implications.
The effect of electrophilic substances: p-bromophenylisothiocyanate (PBITC); fluoresceinisothiocyanate (FITC); [4-isothiocyanatophenyl-(6-thioureidohexyl)-carbamoylmethyl] -ATP (ATPITC); 2,4,6-trinitrobezenesulfonic acid (TNBS); 1-(5-nitro-2-furyl)-2-phenylsulfonyl-2-furylcarbonyl ethylene (FE1); 1-(5-phenylsulfonyl-2-furyl)-2-phenylsulfonyl-2-furylcarb onyl ethylene (FE2) and 1-(5-phenylsulfonyl-2-furyl)-2-phenylsulfonyl-2-tienocarb onyl ethylene (FE3) on the sarcolemmal (Na/K)-ATPase isolated from guinea-pig hearts was studied. FITC and PBITC were found to inhibit competitively the activation of (Na/K)-ATPase by ATP. Being for the enzyme inhibitor and substrate at the same time ATPITC does not offered clear kinetic behavior. However, the activation of (Na/K)-ATPase by sodium and potassium ions was inhibited non-competitively by all three isothiocyanates. These data indicated that isothiocyanates may interact predominantly in the ATP-binding site of the enzyme molecule. In contrary to isothiocyanates TNBS and FE1 (FE2 and FE3 were ineffective) inhibited the activation of (Na/K)-ATPase by ATP non-competitively i.e., their interaction in the ATP-binding site seemed to be improbable. Nevertheless, TNBS and FE1 both manifested affinities to that moiety of (Na/K)-ATPase molecule which is binding potassium. More specific was the effect of FE1 that showed clearly competitive inhibition of potassium-stimulation of the enzyme activity. FE1 exerted also an ouabain-like effect on the mechanical activity of isolated perfused guinea-pig heart. This result indicates that FE1 seems to exert a selective inhibition of the (Na/K)-ATPase not only in vitro but also in integrated cardiac tissue.
Adenosine Triphosphate↗
Comparison of ATP binding in the active sites of (Na+ + K(+)-ATPase, Mg(2+)-ATPase and Ca(2+)-ATPase with low affinity to calcium from cardiac sarcolemma.
The chemical composition of the active sites of cardiac sarcolemmal (Na+ + K(+)-ATPase, Mg(2+)-ATPase and Ca(2+)-ATPase has not been determined definitely. The present study deals with investigation of the role of OH group in position two on the ribose moiety of the ATP molecule in its interaction with the specific ATP binding sites on the above ATPases. Experiments with application of ATP and deoxyATP (the OH group in position 2 on the ribose absent revealed that neither Ca(2+)-ATPase nor Mg(2+)-ATPase is able to distinguish between ATP and deoxyATP as substrates). This indicates that the OH group investigated may play a negligible role only in ATP binding and splitting by the latter ATPases. On the contrary, kinetic studies of Na+ + K(+)-ATPase activation by deoxyATP revealed that the latter compound is a considerably less suitable substrate for the enzyme than ATP. Consequently the OH group in position 2 on the ribose moiety proved to be important both for ATP binding in the active site and for proper substrate turnover by (Na+ + K(+)-ATPase interaction of the ATP binding site of heart sarcolemmal ATPases. Results of the experiments showed that Ca(2+)-ATPase and Mg(2+)-ATPase cannot distinguish between ATP and deoxyATP as substrates. Kinetic studies of (Na+ + K+)-ATPase activation by deoxyATP revealed that the latter is a considerably less good substrate for the enzyme than ATP. It means that the OH group in position two on the ribose moiety proved to be important for both binding of ATP in the active site and for proper substrate turnover by (Na+ + K+)-ATPase.
Adenosine Triphosphatases↗
Influence of calcium antagonists on heart sarcolemmal (Na+ + K(+)-ATPase.
The effect of calcium entry blocking agents nitrendipine and flunarizine on Mg(2+)-ATPase, (Mg2+ + Na(+)-ATPase, (Na+ + K(+)-ATPase and (Mg2+ + Ca(2+)-ATPase activities was studied. Nitrendipine (1 mumol/l-1) exerted a stimulatory effect on (Mg2+ + Na(+)-ATPase activity. Kinetic analysis of this effect revealed a two-fold rise in Vmax value and lowered Km value for activation of the enzyme by Na+ ions. In concentrations 10(-7) and 10(-5) mol.l-1 flunarizine behaved as a non-specific inhibitor of all sarcolemmal ATPases investigated. Nevertheless, in concentration of 10(-6) mol.l-1 flunarizine inhibited selectively the (Mg2+ + Na(+)-ATPase and (Na+ + K(+)-ATPase activities of myocardial sarcolemma. These observations provided evidence that both flunarizine and nitrendipine, in the concentration 10(-6) mol.l-1, modulate the (Mg2+ + Na(+)-ATPase and (Na+ + K(+)-ATPase activities in cardiac sarcolemma. These side effects of the above drugs particularly that of nitrendipine might have potential physiological relevance.
Adenosine Triphosphatases↗