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PubMed1976

Amino acid transport in isolated rat thymocytes. Effects of divalent cations and ethanol.

In dispersed rat thymocytes neither basal alpha-aminoisobutyric acid influx nor influx stimulated by insulin, prostaglandin theophylline, or butyryl adenosine 3':5'-monophosphate (cyclic AMP) depended on extracellular calcium or magnesium. The divalent cation ionophore A23187 inhibited both basal and stimulated alpha-aminoisobutyric acid influx. The extent to which influx was inhibited depended on ionophore concentration, extracellular calcium concentration, and time but did not depend on extracellular magnesium. Significant inhibition could be detected at an ionophore concentration of 1 muM and maximal inhibition occurred with 6 muM A23187. A23187 increased cellular uptake of calcium and there was good agred calcium uptake and that for ionophore inhibition of alpha-aminoisobutyric acid influx. Incubating cells with A23187 and then adding ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N',-tetraacetic acid completely reversed ionophore-stimulated cellular calcum uptake but did not reverse inhibition of alpha-aminoisobutyric acid influx. Thus, A23187 produces irreversible inhibition of alpha-aminoisobutyric acid transport in dispersed rat thymocytes. Ethanol abolished insulin-stimulated alpha-aminoisobutyric acid influx but did not alter basal influx or that stimulated by prostaglandin E1, theophylline, or N6,O2'-dibutyryl adenosine 3':5'-monophosphate. Inhibition could be detected with 0.2% (v/v) ethanol and insulin-stimulated alpha-aminoisobutyric influx was abolished with 1% ethanol. The effect of ethanol occurred immediately and could be reversed completely. This ability of ethanol to inhibit selectively insulin-stimulated alpha-aminoisobutyric acid influx indicates that the mechanism through which insulin stimulates alpha-aminoisobutyric acid influx is functionally distinct from the stimulation produced by cyclic AMP.

Aminoisobutyric Acids↗
PubMed1999

Depletion of divalent cations within the secretory pathway inhibits the terminal glycosylation of complex carbohydrates of thyroglobulin.

Newly synthesized thyroglobulin transiting the secretory pathway is posttranslationally modified by addition of oligosaccharides to asparagine N-linked residues. The effect of divalent cation depletion on oligosaccharide processing of Tg was studied in FRTL-5 cells. Treatment with an ionophore, A23187, or thapsigargin, an inhibitor of the sarcoplasmic/endoplasmic reticulum ATPases delayed Tg secretion. These effects were accompanied by a normal distribution of the marker of the endoplasmic reticulum protein disulfide isomerase. Analysis of the thyroglobulin oligosaccharides by Bio-gel P4 chromatography showed that in the presence of A23187 and thapsigargin the addition of peripheral sialic acid and possibly galactose is inhibited. These findings were strengthened by experiments of exoglycosidase digestion and SDS-PAGE analysis of the resulting products. These results reveal a cellular mechanism of production of thyroglobulin with incompletely processed complex chains, i.e., the ligand of the recently described GlcNAc and asialoglycoprotein receptors of the thyroid. Since A23187 and thapsigargin inhibit biosynthetically the addition of peripheral sugars on N-linked oligosaccharides chains, the thyroglobulin molecules secreted in the presence of A23187 and thapsigargin should greatly facilitate studies on the function of the GlcNAc and asialoglycoprotein receptors of the thyroid.

Animals↗
PubMed1985

Somatomedin synthesis by a subclone of Buffalo rat liver cells. Influence of divalent cations on rIGF-II release.

Previous studies have provided evidence that biosynthesis and secretion of somatomedin (SM) is not only hormone dependent, but also modulated by nutritional factors. Little is known, however, about the role of divalent cations in these processes. A subclone of Buffalo rat liver (BRL) cells, known to secrete rat insulin-like growth factor-II (rIGF-II) into serum-free medium, was used to define the influence of Ca2+, Mg2+ and Zn2+ on this function. The secretion of rIGF-II by subclone BRL-3SC appears to be quite stable in minimal essential medium (MEM) over a wide range in Ca2+ concentrations (0.18-3.0 mM) but is reduced to only 8% of controls in the absence of Ca2+ (P less than 0.01). Reducing, and even eliminating, the extracellular concentration of Mg2+ alone caused no change in basal rIGF-II release, while simultaneously decreasing Mg2+ and Ca2+ results in a marked drop in the secretion of this SM, reaching a nadir of 38% of controls in the absence of Mg2+ (P less than 0.001). A Mg2+ concentration of 10 mM, or 25 times 'normal', did not alter the basal secretion of rIGF-II. Eliminating the trace amount (0.8 nM) of Zn2+ in MEM by chelation with EDTA decreased rIGF-II secretion to 62% of control levels (P less than 0.01), while increasing the concentration of this cation to 3 mM did not alter the basal release of this SM. Decreased rIGF-II release in the presence of EGTA and EDTA is not due to irreversible cell damage since the secretion of this SM was restored to normal during subsequent reincubation in MEM alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Ionic modulation of the effects of heparin and 6-aminohexanoic acid on plasminogen activation by streptokinase: the role of ionic strength, divalent cations and chloride.

Studies were conducted on the effect of heparin or 6-aminohexanoic acid (6-AH) on the activation of glutamic plasminogen (Glu-Plg) by streptokinase in the presence of different concentrations of buffer, NaCl and divalent cations. Heparin and 6-AH inhibited streptokinase-mediated activation of Glu-Plg using 10 mM Tris-HCl buffer pH 7.4. This inhibition was partially reversed by the addition of 0.2-1.0 mM of Mg ions. Increasing the ionic strength of Tris-HCl buffer from 10 to 50 mM or addition of 50-150 mM of NaCl to 50 mM Tris-HCl pH 7.4 inhibited the activation of Glu-Plg by streptokinase while decreasing the % inhibition by heparin over the control samples. Double reciprocal plot of the activation of Glu-Plg by streptokinase using 50 mM Tris-HCl pH 7.4 containing 100 mM NaCl showed that the addition of heparin lowered Vmax by 50% without affecting Km. To determine whether the inhibitory effect of heparin was specifically directed towards Glu-Plg or streptokinase, the ratios of the initial rate of plasmin generation in the presence of heparin over the controls were plotted against the inverse of the volume fraction of Glu-Plg or streptokinase after serial dilutions. The results indicated that the dilutions of streptokinase but not of Glu-Plg influenced the ratios, suggesting an interaction of heparin with streptokinase. Addition of 6-AH reversed the inhibitory effect of NaCl on the activation of Glu-Plg by streptokinase and the results of the near UV CD spectra of Glu-Plg showed that addition of 6-AH enhanced the spectra in this region with an increase in the ellipticity which was not affected by addition of NaCl.

Aminocaproic Acid↗
PubMed1994

Dual divalent cation requirement of the MutT dGTPase. Kinetic and magnetic resonance studies of the metal and substrate complexes.

Kinetic analyses of both the Mn(2+)- and Mg(2+)-activated hydrolysis of dGTP by MutT show the requirement for two divalent cations. Whereas Mn2+ supports a 20-fold lower kcat (0.19 s-1) than Mg2+ (4.0 s-1), the Km of Mn2+.dGTP (6.3 microM) is 45-fold lower than that of Mg2+.dGTP (284 microM). Adenosine 5'-(alpha,beta-methylenetriphosphate) (AMPCPP) is a linear competitive inhibitor with respect to dGTP with a Ki for Mg2+.AMPCPP (42 microM) which is 57-fold lower than the Ki of Mg2+.AMPCPP (2.4 mM). Such tightening suggests that a metal-bridge E.M2+.NTP.M2+ complex is the catalytically active species. The 12 dissociation constants describing the quaternary MutT.M2+.AMPCPP.M2+ complex were evaluated for both Mn2+ and Mg2+, using EPR and NMR methods. MutT binds a single Mn2+ with a Kd of 130 +/- 40 microM in reasonable agreement with the kinetically determined activator constant of Mn2+ of 230 +/- 72 microM. The MutT.AMPCPP complex binds two Mn2+ ions, the weaker of which has a Kd of 16 +/- 2 microM in agreement with the kinetically determined KmMn2+ of 26 +/- 10 microM. MutT.Mn2+ binds Mn2+.AMPCPP with Kd of 16 +/- 4 microM, whereas MutT alone binds Mn2+.AMPCPP with a Kd of 135 +/- 30 microM. The 17-fold enhanced paramagnetic effect of Mn2+ on the longitudinal relaxation rate of water protons found with the binary MutT.Mn2+ complex decreases to 4.7-fold upon binding of AMPCPP and to 8.7-fold upon binding of Mn2+.AMPCPP, further supporting a metal-bridge MutT.M2+.NTP.M2+ complex. By competition with Mn2+ MutT binds Mg2+ at one site with a Kd of 7.5 mM, and MutT.AMPCPP binds Mg2+ at two sites, the weaker of which has a Kd of 0.9 mM. These values are comparable to the kinetically determined KaMg of 15 +/- 7 mM and KmMg of 1.7 +/- 0.7 mM, respectively. Studies with the racemic, substitution-inert beta, gamma-bidentate tetraamminecobalt (III)-beta,gamma-phosphate-ATP (Co3+(NH3)4ATP) complex show that MutT slowly hydrolyzes only the lambda stereoisomer but requires Mg2+ or Mn2+ to do so, confirming a dual metal ion requirement.

Adenosine Triphosphate↗
PubMed1986

Membrane damage by hemolytic viruses, toxins, complement, and other cytotoxic agents. A common mechanism blocked by divalent cations.

Hemolytic viruses, bacterial and animal toxins, the components of activated complement, cationic proteins, and detergents induce a sequence of permeability changes at the plasma membrane that are in every case sensitive to changes in ionic strength and to divalent cations. Individually, each agent exhibits positive cooperativity; when two agents are present together, they show synergy. It is concluded that such cytotoxic agents damage membranes by a common mechanism. Hence permeability changes are unlikely to depend on the formation of specific, protein-lined channels, as previously envisaged in the case of activated complement or certain bacterial toxins.

Animals↗
PubMed1986

Inhibition by divalent cations and sulphydryl reagents of the passive Ca2+ transport in human red blood cells observed in the presence of vanadate.

The uptake of 45Ca2+ by human red blood cells induced by vanadate was found to be inhibited by a number of divalent cations. The following order of potencies was determined (in parentheses, IC50 in mmol/l): Cu2+ (0.006), Zn2+ (0.014), Cd2+ (0.030), Co2+ (0.20), Ni2+ (0.25), Mn2+ (8.0), Ba2+ (9.0), Sr2+ (14.0). The effects of Cu2+, Zn2+ and Cd2+ were biphasic--over a critical concentration their inhibitory potencies decreased, and finally, were lost. Besides Ca2+, Sr2+, Ba2+ and Mn2+ were also taken up, but only Ca2+ and Sr2+ were capable of eliciting the Gárdos effect. Ni2+ was not taken up. Several HS reagents also inhibited 45Ca2+ uptake. The following order of potencies was determined (in parentheses, IC50 in mmol/l): mersalyl (0.0025), 5,5'-dithiobis(2,2'-dinitrobenzoic acid) (0.011), p-chloromercuric acid (0.042), N-ethylmaleimide (2.0). The effects of all HS reagents except N-ethylmaleimide were biphasic. The biphasicity of the actions of the indicated agents was caused by the opening of a new pathway for 45Ca2+ entry which is different from that observed in the presence of vanadate alone, and is inhibited by low concentrations of these agents. The modified form of the anion channel seems to be identical with the former pathway. The last one is mediated by a transport protein which has an ionic specificity similar to Ca2+ channels in excitable tissues, and contains an HS group which is essential for the transport function.

Biological Transport↗
PubMed1998

N-stearoyl-phosphatidylserine: synthesis and role in divalent-cation-induced aggregation and fusion.

N-Acylphosphatidylserines have been isolated from intact and injured tissues, but the participation of such acidic phospholipids in membrane aggregation and fusion has not been demonstrated. We have synthesized N-stearoylphosphatidylserine (NSPS) and examined divalent-cation-induced aggregation of NSPS-liposomes, which leads to membrane destabilization and fusion. The purified lipid was characterized by its chromatographic and spectroscopic (infrared and 1H nuclear magnetic resonance) properties and by its chemical degradation pattern. Aggregation of unilamellar NSPS-liposomes was studied as a function of calcium and magnesium concentration. The ability of calcium and magnesium to induce vesicle aggregation is higher for phosphatidylserine (PS)-liposomes (threshold concentration 1.5 mM for calcium and 4.6 mM for magnesium) than for NSPS-liposomes (threshold concentration 2.8 mM for calcium and 6.6 mM for magnesium). The irreversibility of the aggregation reactions after adding EDTA suggests that vesicle fusion might occur in the presence of calcium and magnesium. Preliminary studies, based on mixing of both lipid and internal aqueous contents, show that fusion rather than aggregation of NSPS-liposomes occurs in the presence of calcium ions. The tendency of NSPS-liposomes to aggregate at higher cation concentrations than PS-liposomes suggests that N-acylation of phosphatidylserine protects the membrane against degenerative damage caused by aggregation and fusion.

Cations, Divalent↗
PubMed1987

Divalent cations reduce depolarization of primary afferent terminations by GABA.

Divalent metal cations, including zinc, cadmium, cobalt, nickel, strontium, manganese, magnesium and calcium, reduced the depolarization by microelectrophoretic gamma-aminobutyric acid (GABA) and piperidine-4-sulphonic acid of the central terminations of muscle group Ia primary afferent fibres in the cat spinal cord without affecting the inhibition by GABA of the firing of spinal interneurones. There thus appears to be a difference in either the interaction of GABA with recognition sites, or in the mechanism by which such interaction activates chloride ionophores, at GABA-mediated bicuculline-sensitive synapses on the central terminals of peripheral primary afferent neurones and those on neurones located within the central nervous system.

Action Potentials↗
PubMed1982

Divalent cations and chlorpromazine can induce non-bilayer structures in phosphatidic acid-containing model membranes.

(1) The structural organization of aqueous dispersions of 1,2-dioleoylphosphatidic acid has been investigated by freeze-fracture electron microscopy in relation to variations in pH, divalent cations and the local anaesthetic chlorpromazine. (2) In the pH range 4--8 in the presence of 100 mM Na+, dioleoylphosphatidic acid is organized in bilayers. (3) At pH 6 and not at pH 4 and 8.5 addition of Ca2+, Mg2+, Mn2+ and chlorpromazine results in the formation of the hexagonal HII phase. (4) Ca2+ and chlorpromazine addition to mixed phosphatidylcholine-dioleoylphosphatidic acid bilayers at pH 6 results in the formation of lipidic particles.

Calcium↗
PubMed1996

Effects of the type of divalent cation, Ca2+ or Mg2+, bound at the high-affinity site and of the ionic composition of the solution on the structure of F-actin.

F-actins containing either Ca2+ or Mg2+ at the single high-affinity site for a divalent cation differ in their dynamic properties [Carlier (1991) J. Biol. Chem. 266, 1-4]. In an attempt to obtain information on the structural basis of this difference, we probed the conformation of specific sites in the subunits of Mg- and Ca-F-actin with limited proteolysis by subtilisin and trypsin. The influence of the kind of polymerizing salt was also investigated. At high proteinase concentrations required for digestion of actin in the polymer form, subtilisin gives a complex fragmentation pattern. In addition to the earlier known cleavage between Met47 and Gly48 in the DNAse-I-binding loop, cleavage of F-actin between Ser234 and Ser235 in subdomain 4 has recently been reported [Vahdat, Miller, Phillips, Muhlrad and Reisler (1995) FEBS Lett. 365, 149-151]. Here we show that actually a larger segment, comprising residues 227-235, is removed and the bond between Leu67 and Lys68 in subdomain 2 is split in both G- and F-actin, and that the differences in the fragmentation patterns of the G- and F-forms are accounted for by the protection of the bond 47-48 in F-actin. The subtilisin and trypsin cleavage sites in segment 61-69, subtilisin sites in segment 227-235 and trypsin sites between Lys373 and Cys374 were less accessible in Mg-F-actin than in Ca-F-actin. These are intramolecular effects, as similar changes were observed on Ca2+/Mg2+ replacement in G-actin. The cation-dependent effects, in particular those on segment 61-69, were however less pronounced in F-actin than in G-actin. The results suggest that substitution of Mg2+ for Ca2+, and KCl-induced polymerization of CaATP-G-actin, bring about a similar change in the conformation of subdomain 2 of the monomer. The presence of Mg2+ at the high-affinity site also resulted in an increased protection of the bond 47-48. This latter appears to be an intermolecular effect because it is specific for F-actin. The susceptibility to subtilisin and trypsin was also strongly influenced by the kind and concentration of polymerizing salt. The digestion patterns suggest that the exposure and/or flexibility of the regions containing the cleavage sites diminish with enhancement of the ionic strength of the solution. The results are discussed in terms of the current models of F-actin.

Actins↗
PubMed2000

Ecosystems supporting clusters of sporadic TSEs demonstrate excesses of the radical-generating divalent cation manganese and deficiencies of antioxidant co factors Cu, Se, Fe, Zn. Does a foreign cation substitution at prion protein's Cu domain initiate TSE?

Analyses of food chains supporting isolated clusters of sporadic TSEs (CWD in N Colorado, scrapie in Iceland, CJD in Slovakia) demonstrate a consistent 2 1/2+ fold greater concentration of the pro-oxidant divalent cation, manganese (Mn), in relation to normal levels recorded in adjoining TSE-free localities. Deficiencies of the antioxidant co factors Cu/Se/Zn/Fe and Mg, P and Na were also consistently recorded in TSE foodchains. Similarities between the clinical/pathological profile of TSEs and Mn delayed psycho-neurotoxicity in miners are cited, and a novel theory generated which suggests that sporadic TSE results from early life dependence of TSE susceptible genotypes on ecosystems characterised by this specific pattern of mineral imbalance. Low Cu/Fe induces an excessive absorption of Mn in ruminants and an increased oxidation of Mn2+ into its pro oxidant species, Mn3+, which accumulates in mitochondria of CNS astrocytes in Mn SOD deficient genotypes. Deficiencies of scavenger co factors Cu/Zn/Se/Fe in the CNS permits Mn3+ initiated chain reactions of auto-oxidant mediated neuronal degeneration to proliferate, which, in turn, up-regulates the expression of the Cu-metalloprotein, prion protein (PrP). Once the rate of PrP turnover and its demand for Cu exceeds the already depleted supply of Cu within the CNS, PrP can no longer bind sufficient Cu to maintain its conformation. Mn3+ substitutes at the vacated Cu domain on PrP, thus priming up a latent capacity for lethal auto-oxidative activity to be carried along with PrP like a 'trojan horse'; where Mn 3+ serves as the integral 'infectious' transmissible component of the misfolded PrP-cation complex. The Mn overactivation of concanavalin A binding to glycoprotein and Mn-initiated autoxidation results in a diverse pathological profile involving receptor capping, aggregation/modification of CNS membrane/cytoskeletal proteins. TSE ensues. The BSE/nv CJD strain entails a 'synthetic' induction of the same CNS mineral disturbance, where 'in utero' exposure to Cu-chelating insecticides/Mn supplements accelerates the onset of a more virulent 'strain' of adolescent TSE.

Amino Acid Sequence↗
PubMed1993

Effect of divalent cations in bacteriological media on the susceptibility of Xanthomonas maltophilia to imipenem, with special reference to zinc ions.

The susceptibility of Xanthomonas maltophilia strains to beta-lactams is known to vary according to the type of growth media used. We have assayed the divalent cation content of various susceptibility testing media and correlated this with the susceptibility to imipenem of 30 strains of X. maltophilia, by calculating the IC50. No correlation was found with Ca++ and Mg++ content (r = 0.005, P = 0.99), but a highly significant correlation with the Zn++ content (7.7-42.7 mumol/L) of the medium was found (r = 0.93, P = 0.003). The effect of Zn++ on the susceptibility of X. maltophilia to imipenem was further investigated by adding varying amounts of zinc sulphate to Oxoid Mueller-Hinton agar which has a low Zn++ content (14.2 mumol/L). A highly significant correlation between the Zn++ content and the IC50 was observed (r = 0.95, P = 0.001). Some variability was seen from one series of IC50 determinations to another and samples of ultra-pure water were processed in exactly the same fashion as the agar media and then assayed for cation content. No significant increase in Ca++ or Mg++ content of the water were observed but water autoclaved in universal containers with metal caps and rubber washers acquired up to 40 mumol/L of Zn++. Studies of the correlation between in-vitro sensitivity tests and the clinical performance of beta-lactams used against X. maltophilia will need to take account of the Zn++ content of the susceptibility testing media used.

Anti-Bacterial Agents↗
PubMed1987

Effects of divalent cations on acetylcholine release from digitonin-permeabilized rat cortical synaptosomes.

A preparation of rat brain synaptosomes, partially permeabilized by the cholesterol-specific detergent digitonin, was developed to study the effects of the heavy metals Pb+2 and Cd+2 and of other divalent cations on acetylcholine release from nerve terminals. Consistent with the cation specificities of the transmitter release process in intact nerve terminals, 100 microM free Ba+2, Sr+2 and Ca+2 each induced a release of acetylcholine (ACh) while Ni+2, Co+2 and Mn+2 did not. 100 microM Pb+2 and Cd+2 also induced a release of ACh from the permeabilized synaptosomes. This suggests that, similar to Ba+2 and Sr+2, both Pb+2 and Cd+2 may induce transmitter release through a direct action on the transmitter release apparatus.

Acetylcholine↗
PubMed1981

Organization in the cell nucleus: divalent cations modulate the distribution of condensed and diffuse chromatin.

The organization of rat liver nuclei in vitro depends on the ionic milieu. Turbidity measurements of nuclear suspensions in the presence of varying concentrations of divalent cations have been correlated with nuclear ultrastructure. The concentration of MgCl2 (2 mM) at which turbidity of nuclear suspensions is maximal and chromatin condensation appears most extensive is the same concentration that reportedly (Gottesfeld et al., 1974, Proc. Natl. Acad. Sci. U. S. A. 71:2193-2197) precipitates "inactive" chromatin. Thus, a mechanism is suggested by which chromatin activity and ultrastructural organization within the nucleus may be mediated. The nuclear organizational changes attendant upon the decrease in divalent cation concentration were not entirely reversible.

Animals↗
PubMed1992

Divalent cation regulation of the function of the leukocyte integrin LFA-1.

The integrin lymphocyte function-associated antigen-1 (LFA-1) expressed on T cells serves as a useful model for analysis of leukocyte integrin functional activity. We have assessed the role of divalent cations Mg2+, Ca2+, and Mn2+ in LFA-1 binding to ligand intercellular adhesion molecule-1 (ICAM-1) and induction of the divalent cation-dependent epitope recognized by mAb 24. Manganese strongly promoted both expression of the 24 epitope and T cell binding to ICAM-1 via LFA-1, suggesting that Mn2+ is able to directly alter the conformation of LFA-1 in a manner that favors ligand binding. Since Mn2+ also promotes functional activity of other integrins, parallels in mechanism of ligand binding may span the integrin family. In contrast, induction of 24 epitope expression by Mg2+ required removal of Ca2+ from T cell LFA-1 with EGTA. Furthermore, binding of mAb 24 to T cell LFA-1 in the presence of either Mn2+ or Mg2+ was found to be specifically inhibited by Ca2+, suggestive of a negative regulatory role for Ca2+ in the control of leukocyte integrin function. Analysis of T cell binding to ICAM-1 via LFA-1 in the presence of Mg2+ or Mn2+, confirmed that Ca2+ exerted inhibitory effects upon LFA-1 function. The implication of our findings is that Ca2+ bound with relatively high affinity to LFA-1 may serve to maintain an inactive state. Thus induction of function and 24 epitope expression may occur as a result of displacement of Ca2+ from leukocyte integrins or alternatively, such activators may be able to impose the required conformational change in the presence of bound Ca2+.

Animals↗
PubMed1970

Divalent cation stimulation of substrate oxidation by corn mitochondria.

The oxidation of reduced nicotinamide adenine dinucleotide, malate-pyruvate, and succinate by corn mitochondria in buffered 0.2 m KCl was determined as a function of divalent cations. Ni(2+), Mg(2+), Co(2+), Ca(2+), Mn(2+), Sr(2+), and Ba(2+) stimulated reduced nicotinamide adenine dinucleotide oxidation in the absence of inorganic phosphate, with Ca(2+) and Sr(2+) having the greatest effect. Malate-pyruvate and succinate oxidation was stimulated by Ca(2+), Ba(2+), and Sr(2+), but only in the presence of inorganic phosphate. Ca(2+), Sr(2+), and Ba(2+) produced a simulated state 4 to state 3 transition with all three substrates, but only with malate-pyruvate and succinate was there a return to state 4. The order of divalent cation effectiveness suggests that the rate of water substitution from the cation inner coordination hydration sphere may be a rate-limiting step in certain mitochondrial reactions involving electron transport and phosphorylation.

Journal Article↗