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1.
A comparative study between a brain Na+,K(+)-ATPase inhibitor (endobain E) and ascorbic acid 总被引:1,自引:0,他引:1
In the search of Na+,K+-ATPase modulators, we have reported the isolation by gel filtration and HPLC of a brain fraction, termed endobain E, which highly inhibits Na+,K+-ATPase activity. In the present study we compared some properties of endobain E with those of ascorbic acid. Kinetic experiments assaying synaptosomal membrane K+-p-nitrophenylphosphatase (K+-p-NPPase) activity in the presence of endobain E or ascorbic acid showed that in neither case did enzyme inhibition prove competitive in nature versus K+ or p-NPP concentration. At pH 5.0, endobain E and ascorbic acid maximal UV absorbance was 266 and 258 nm, respectively; alkalinization to pH 14.0 led to absorption drop and shift for endobain E but to absorbance disappearance for ascorbic acid. After cysteine treatment, endobain E absorbance decreased, whereas that of ascorbic acid remained unaltered; iodine treatment led to absorbance drop and shift for endobain E but to absorbance disappearance for ascorbic acid. HPLC analysis of endobain E disclosed the presence of two components: one eluting with retention time and UV spectrum indistinguishable from those of ascorbic acid and a second, as yet unidentified, both exerting Na+,K+-ATPase inhibition. 相似文献
2.
Guennoun-Lehmann S Fonseca JE Horisberger JD Rakowski RF 《The Journal of membrane biology》2007,216(2-3):107-116
Palytoxin (PTX) opens a pathway for ions to pass through Na,K-ATPase. We investigate here whether PTX also acts on nongastric
H,K-ATPases. The following combinations of cRNA were expressed in Xenopus laevis oocytes: Bufo marinus bladder H,K-ATPase α2- and Na,K-ATPase β2-subunits; Bufo Na,K-ATPase α1- and Na,K-ATPase β2-subunits; and Bufo Na,K-ATPase β2-subunit alone. The response to PTX was measured after blocking endogenous Xenopus Na,K-ATPase with 10 μm ouabain. Functional expression was confirmed by measuring 86Rb uptake. PTX (5 nm) produced a large increase of membrane conductance in oocytes expressing Bufo Na,K-ATPase, but no significant increase occurred in oocytes expressing Bufo H,K-ATPase or in those injected with Bufo β2-subunit alone. Expression of the following combinations of cDNA was investigated in HeLa cells: rat colonic H,K-ATPase α1-subunit and Na,K-ATPase β1-subunit; rat Na,K-ATPase α2-subunit and Na,K-ATPase β2-subunit; and rat Na,K-ATPase β1- or Na,K-ATPase β2-subunit alone. Measurement of increases in 86Rb uptake confirmed that both rat Na,K and H,K pumps were functional in HeLa cells expressing rat colonic HKα1/NKβ1 and NKα2/NKβ2. Whole-cell patch-clamp measurements in HeLa cells expressing rat colonic HKα1/NKβ1 exposed to 100 nm PTX showed no significant increase of membrane current, and there was no membrane conductance increase in HeLa cells transfected
with rat NKβ1- or rat NKβ2-subunit alone. However, in HeLa cells expressing rat NKα2/NKβ2, outward current was observed after pump activation by 20 mm K+ and a large membrane conductance increase occurred after 100 nm PTX. We conclude that nongastric H,K-ATPases are not sensitive to PTX when expressed in these cells, whereas PTX does act
on Na,K-ATPase. 相似文献
3.
Georgina Rodríguez de Lores Arnaiz 《Molecular neurobiology》1992,6(4):359-375
The arrival of the nerve impulse to the nerve endings leads to a series of events involving the entry of sodium and the exit
of potassium. Restoration of ionic equilibria of sodium and potassium through the membrane is carried out by the sodium/potassium
pump, that is the enzyme Na+,K+-ATPase. This is a particle-bound enzyme that concentrates in the nerve ending or synaptosomal membranes. The activity of
Na+,K+-ATPase is essential for the maintenance of numerous reactions, as demonstrated in the isolated synaptosomes. This lends interest
to the knowledge of the possible regulatory mechanisms of Na+,K+-ATPase activity in the synaptic region. The aim of this review is to summarize the results obtained in the author's laboratory,
that refer to the effect of neurotransmitters and endogenous substances on Na+,K+-ATPase activity. Mention is also made of results in the field obtained in other laboratories.
Evidence showing that brain Na+,K+-ATPase activity may be modified by certain neurotransmitters and insulin have been presented. The type of change produced
by noradrenaline, dopamine, and serotonin on synaptosomal membrane Na+,K+-ATPase was found to depend on the presence or absence of a soluble brain fraction. The soluble brain fraction itself was
able to stimulate or inhibit the enzyme, an effect that was dependent in turn on the time elapsed between preparation and
use of the fraction.
The filtration of soluble brain fraction through Sephadex G-50 allowed the separation of two active subfractions: peaks I
and II. Peak I increased Na+,K+- and Mg2+-ATPases, and peak II inhibited Na+,K+-ATPase. Other membrane enzymes such as acetylcholinesterase and 5′-nucleotidase were unchanged by peaks I or II.
In normotensive anesthetized rats, water and sodium excretion were not modified by peak I but were increased by peak II, thus
resembling ouabain effects.3H-ouabain binding was unchanged by peak I but decreased by peak II in some areas of the CNS assayed by quantitative autoradiography
and in synaptosomal membranes assayed by a filtration technique. The effects of peak I and II on Na+,K+-ATPase were reversed by catecholamines. The extent of Na+,K+-ATPase inhibition by peak II was dependent on K+ concentration, thus suggesting an interference with the K+ site of the enzyme. Peak II was able to induce the release of neurotransmitter stored in the synaptic vesicles in a way similar
to ouabain. Taking into account that peak II inhibits only Na+,K+-ATPase, increases diuresis and natriuresis, blocks high affinity3H-ouabain binding, and induces neurotransmitter release, it is suggested that it contains an ouabain-like substance. 相似文献
4.
Pellegrino de Iraldi A Peña C Rodríguez de Lores Arnaiz G 《Cellular and molecular neurobiology》2003,23(2):131-141
1. The purpose of the present study was to analyze the possible effect of ouabain and an endogenous ouabain-like substance (endobain E), on lenses of 100- and 400-g body weight rats.2. Lenses were incubated with ouabain or endobain E for 120 min, either at room temperature or in the cold; opalescence was checked by gross examination and ultrastructure by electron microscopy.3. Lenses from 400-g rats invariably remained translucent whereas those from 100-g rats presented variable opalescence.4. As disclosed with the electron microscope, lenses of 100-g rats incubated at room temperature, with or without ouabain or endobain E, presented variable degrees of ultrastructural changes: with ouabain, there was fiber separation and vacuole formation but with endobain E, no vacuoles were found and fibers, though disorganized, appeared attached. After incubation in an ice bath, lenses were markedly altered in all conditions assayed.5. It is concluded that ouabain and endobain E effect on lens transparency depends on the rat age and that in young animals, it is crucial incubation temperature during experimental procedure. 相似文献
5.
The Na+, K+-ATPase activity and its response to vanadate inhibition was investigated in cerebral cortex homogenates of 7-, 12- and 18-day-old rats. The enzyme was inhibited by vanadate in a dose-dependent manner in all these age groups. Furthermore, there was a different sensitivity towards vanadate during postnatal development; the concentration of V+5 needed for 50% inhibiton of Na+, K+-ATPase was 1.1×10–6M, 2×10–7M and 4.4×10–7M for 7-, 12- and 18-day-old rats, respectively. It is suggested that the different sensitivity of Na+, K+-ATPase towards vanadate inhibition during postnatal development might be due to age-dependent changes in the ratio of various cell types.Special Issue dedicated to Dr. O. H. Lowry. 相似文献
6.
We studied Na(+), K(+)-ATPase activity alpha isoforms by performing ouabain inhibition curves in rat hypothalamus and mesencephalon after acute administration of desipramine to rats. In hypothalamus, Ki values for high, intermediate and low affinity populations were 0.075x10(-9) M, 0.58x10(-6) M and 0.97x10(-3) M, with isoform distribution of 55%, 28% and 17%, respectively. In mesencephalon, Ki values for high, intermediate and low affinity populations were 1.80x10(-9) M, 0.56x10(-6) M and 0.21x10(-3) M, with isoform distribution of 28%, 46% and 21%, respectively. Three hours after acute administration of 10 mg/kg desipramine to rats, Na(+), K(+)-ATPase activity in hypothalamus increased significantly 54%, 39% and 51% as assayed respectively in the absence of ouabain or in the presence of 1x10(-9) M, or 5x10(-6) M ouabain, whereas only a trend was recorded in the presence of 1x10(-3) M ouabain. In such conditions, enzyme activity in mesencephalon increased significantly 73%, 54%, 30% and 271%, respectively. Present results showed that desipramine treatment enhances the activity of Na(+), K(+)-ATPase alpha isoforms in rat hypothalamus and mesencephalon, but the extent of this increase differs according to the isoform and the anatomical area studied, suggesting a differential enzyme regulation in response to noradrenergic stimulation. 相似文献
7.
By means of a Sephadex G-50 column and anionic exchange HPLC a cerebral cortex soluble fraction (II-E) which highly inhibits neuronal Na+-K+-ATPase activity has been previously obtained. Herein, II-E properties are compared with those of the cardenolide ouabain, the selective and specific Na+, K+-ATPase inhibitor. It was observed that alkali treatment destroyed II-E but not ouabain inhibitory activity. II-E presented a maximal absorbance at 265 nm both at pH 7 and pH 2 which diminished at pH 10. Ouabain showed a maximum at 220 nm which was not altered by alkalinization. II-E was not retained in a C-18 column, indicating its hydrophilic nature, whereas ouabain presented a 26-min retention time in reverse phase HPLC. Therefore, it is concluded that the inhibitory factor present in II-E is structurally different to ouabain. 相似文献
8.
The effect of L-arginine on the Na+,K+-ATPase activity in rat aorta endothelium was studied at its physiological concentrations in the range of 10–6-10–3 M. The enzyme activity was 35.5% increased by low concentrations of L-arginine (10–5 M) and its activity was 32.3-37.1% decreased at the L-arginine concentrations of 10–4-10–3 M. A similar inhibition (by 34.5-42.8%) was also found in the presence of a NO-donor nitroglycerol (10–4-10–3 M). An optical isomer of L-arginine, D-arginine, at the concentrations of 10–5 M also increased the enzyme activity by 37.1%, but its inhibiting effect was much less pronounced and was 15.7% at the D-arginine concentration of 10–3 M. An inhibitor of NO-synthase, L-NAME (NG-nitroarginine, methyl ester), failed to inhibit Na+,K+-ATPase. However, the presence of L-NAME abolished the inhibition of Na+,K+-ATPase by high concentrations of L-arginine. Thus, the effect of L-arginine on the endothelial Na+-pump depended on its concentration, and it is suggested that the enzyme inhibition by high concentrations of L-arginine should be associated with activation of the endogenous synthesis of NO. 相似文献
9.
Georgina Rodríguez de Lores Arnaiz 《Neurochemical research》1990,15(3):289-294
Previous evidence from this laboratory indicated that catecholamines and brain endogenous factors modulate Na+, K+-ATPase activity of the synaptosomal membranes. The filtration of a brain total soluble fraction through Sephadex G-50 permitted the separation of two fractions-peaks I and II-which stimulated and inhibited Na+, K+-ATPase, respectively (Rodríguez de Lores Arnaiz and Antonelli de Gomez de Lima, Neurochem. Res.11, 1986, 933). In order to study tissue specificity a rat kidney total soluble was fractionated in Sephadex G-50 and kidney peak I and II fractions were separated; as control, a total soluble fraction prepared from rat cerebral cortex was also processed. The UV absorbance profile of the kidney total soluble showed two zones and was similar to the profile of the brain total soluble. Synaptosomal membranes Na+, K+- and Mg2+-ATPases were stimulated 60–100% in the presence of kidney and cerebral cortex peak I; Na+, K+-ATPase was inhibited 35–65% by kidney peak II and 60–80% by brain peak II. Mg2+-ATPase activity was not modified by peak II fractions. ATPases activity of a kidney crude microsomal fraction was not modified by kidney peak I or brain peak II, and was slightly increased by kidney peak II or brain peak I. Kidney purified Na+, K+-ATPase was increased 16–20% by brain peak I and II fractions. These findings indicate that modulatory factors of ATPase activity are not exclusive to the brain. On the contrary, there might be tissue specificity with respect to the enzyme source. 相似文献
10.
Herbin Teresa Peña Clara de Lores Arnaiz Georgina Rodríguez 《Neurochemical research》1998,23(1):33-37
Previous work from this laboratory led to the isolation by gel filtration and anionic exchange HPLC of a rat brain fraction named II-E, which highly inhibits synaptosomal membrane Na+, K+-ATPase activity. In this study we evaluated the kinetics of such inhibition and found that inhibitory potency was independent of Na+(1.56–200 mM), K+(1.25–40 mM), or ATP (1–8 mM) concentration. Hanes-Woolf plots indicated that II-E decreases Vmax but does not alter KMvalue, and suggested uncompetitive inhibition for Na+, K+or ATP. However, II-E became a stimulator at 0.5 mM ATP concentration. It is postulated that this brain factor may modulate ionic transport at synapses, thus participating in central neurotransmission. 相似文献
11.
M. de Gómez de Lima Antonelli G. Rodríguez de Lores Arnaiz 《Neurochemical research》1988,13(3):237-241
In the present study some properties of an inhibitory extract of synaptosomal membrane Na+,K+-ATPase were investigated. This extract (peak II) was prepared by gel filtration in Sephadex G-50 of a soluble fraction of the rat cerebral cortex. Ultrafiltration of peak II through Amicon membranes indicated that the inhibitor has a low MW (<1000). The inhibitory activity was not modified by heating in neutral pH at 95°C for 20 min but it was destroyed by charring in acid pH at 200°C for 120 min. The inhibitory activity decreased by incubation of peak II with carboxypeptidase A. These findings suggest that the factor responsible for the inhibition of Na+,K+-ATPase activity is probably a polypeptide. On the other hand, the inhibition was reverted by the chelators EDTA and EGTA, indicating the participation of an ionic compound as well. The increase of Mg2+ concentration during the enzyme assay did not increase the inhibition, indicating that the ion involved might not be vanadate. It is suggested that both a polypeptide and an ionic compound coparticipate in the inhibitory effect of peak II on Na+,K+-ATPase activity. 相似文献
12.
Mandal Atin K. Roy Koushik Sil Parames C. Yadav Satya P. Sen Parimal C. 《Molecular and cellular biochemistry》2001,223(1-2):7-14
A protein isolated from goat testis cytosol is found to inhibit Na+,K+-ATPase from rat brain microsomes. The inhibitor has been purified by ammonium sulphate precipitation followed by hydroxyapatite column chromatography. The purified fraction appears as a single polypeptide band on 10% SDS-PAGE of approximate molecular mass of 70 kDa. The concentration at which 50% inhibition (I50) occurs is in the nanomolar range. The inhibitor seems to bind Na+,K+-ATPase reversibly at ATP binding site in a competitive manner with ATP, but away from ouabain binding site. It does not affect p-nitrophenyl-phosphatase activity. The inhibitor is found to inhibit the phosphorylation step of the Na+,K+-ATPase. The enhancement of tryptophan fluorescence and changes in CD pattern suggest conformational changes of Na+,K+-ATPase on binding to the inhibitor. Amino acid sequence of the trypsinised fragments show some homology with aldehyde reductase. 相似文献
13.
Pontes ZL Oliveira LS Franzon R Wajner M Wannmacher CM Wyse AT 《Neurochemical research》2001,26(12):1321-1326
Na+,K+-ATPase and Mg2+-ATPase activities were determined in the synaptic plasma membranes from hippocampus of rats subjected to chronic and acute proline administration. Na+,K+-ATPase activity was significantly reduced in chronic and acute treatment by 33% and 40%, respectively. Mg2+-ATPase activity was not altered by any treatment. In another set of experiments, synaptic plasma membranes were prepared from hippocampus and incubated with proline or glutamate at final concentrations ranging from 0.2 to 2.0 mM. Na+,K+-ATPase, but not Mg2+-ATPase was inhibited (30%) by the two amino acids. In addition, competition between proline and glutamate for the enzyme activity was observed, suggesting a common binding site for these amino acids. Considering that Na+,K+-ATPase activity is critical for normal brain function, the results of the present study showing a marked inhibition of this enzyme by proline may be associated with the neurological dysfunction found in patients affected by type II hyperprolinemia. 相似文献
14.
Digitalis-like compounds are recently identified steroids synthesized by the adrenal gland, which resemble the structure of plant cardiac glycosides. These compounds, like the plant steroids, bind to and inhibit the activity of the Na+, K+-ATPase. The possible function of the endogenous digitalis-like compounds has to be evaluated in view of the presence of different isoforms of the Na+, K+-ATPase, which differ in their sensitivity to digitalis. This review focuses on recent published data on the Na+, K+-ATPase inhibitors, the digitalis-like compounds, regarding their structure, biosynthesis and secretion from the adrenal gland, physiological role and pathological implications in diseases such as hypertension and depression. Emphasis is given to studies describing the involvement of these compounds in brain function. 相似文献
15.
Kraemer DM Strizek B Meyer HE Marcus K Drenckhahn D 《European journal of cell biology》2003,82(2):87-92
Na+,K(+)-ATPase is a ubiquitous plasmalemmal membrane protein essential for generation and maintenance of transmembrane Na+ and K+ gradients in virtually all animal cell types. Activity and polarized distribution of renal Na+,(+)-ATPase appears to depend on connection of ankyrin to the spectrin-based membrane cytoskeleton as well as on association with actin filaments. In a previous study we showed copurification and codistribution of renal Na+,K(+)-ATPase not only with ankyrin, spectrin and actin, but also with two further peripheral membrane proteins, pasin 1 and pasin 2. In this paper we show by sequence analysis through mass spectrometry as well as by immunoblotting that pasin 2 is identical to moesin, a member of the FERM (protein 4.1, ezrin, radixin, moesin) protein family, all members of which have been shown to serve as cytoskeletal adaptor molecules. Moreover, we show that recombinant full-length moesin as well as its FERM domain bind to Na+,K(+)-ATPase and that this binding can be inhibited by an antibody specific for the ATPase activity-containing cytoplasmic loop (domain 3) of the Na+,K(+)-ATPase alpha-subunit. This loop has been previously shown to be a site essential for ankyrin binding. These observations indicate that moesin might not only serve as direct linker molecule of Na+,K(+)-ATPase to actin filaments but also modify ankyrin binding at domain 3 of Na+,K(+)-ATPase in a way similar to protein 4.1 modifying the binding of ankyrin to the cytoplasmic domain of the erythrocyte anion exchanger (AE1). 相似文献
16.
Georgina Rodríguez de Lores Arnaiz 《Neurochemical research》1993,18(6):655-661
In previous papers, the isolation of brain soluble fractions able to modify neuronal Na+, K+-ATPase activity has been described. One of those fractions-peak I-stimulates membrane Na+, K+-ATPase while another-peak II-inhibits this enzyme activity, and has other ouabain-like properties. In the present study, synaptosomal membrane Na+, K+-ATPase was analyzed under several experimental conditions, using ATP orp-nitrophenylphosphate (p-NPP) as substrate, in the absence and presence of cerebral cortex peak II. Peak II inhibited K+-p-NPPase activity in a concentration dependent manner. Double reciprocal plots indicated that peak II uncompetitively inhibits K+-p-NPPase activity regarding substrate, Mg2+ and K+ concentration. Peak II failed to block the known K+-p-NPPase stimulation caused by ATP plus Na+. At various K+ concentrations, percentage K+-p-NPPase inhibition by peak II was similar regardless of the ATP plus Na+ presence, indicating lack of correlation with enzyme phosphorylation. Na+, K+-ATPase activity was decreased by peak II depending on K+ concentration. It is postulated that the inhibitory factor(s) present in peak II interfere(s) with enzyme activation by K+. 相似文献
17.
Preconditioning Prevents the Inhibition of Na+,K+-ATPase Activity after Brain Ischemia 总被引:4,自引:0,他引:4
de Souza Wyse AT Streck EL Worm P Wajner A Ritter F Netto CA 《Neurochemical research》2000,25(7):971-975
Application of single transient forebrain ischemia (ISC) in adult Wistar rats, lasting 2 or 10 min, caused inhibition of Na+,K+-ATPase activity in cytoplasmic membrane fractions of hippocampus and cerebral cortex immediately after the event. In the 2-min ISC group followed by 60 min of reperfusion, the enzyme inhibition was maintained in the cortex, while there was an increase in hippocampal enzyme activity; both effects were over 1 day after the event. However, in the 10-min ISC group enzyme inhibition had been maintained for 7 days in both cerebral structures. Interestingly, ischemic preconditioning (2-min plus 10-min ISC, with a 24-hour interval in between) prevented the inhibitory effect of ischemia/reperfusion on Na+,K+-ATPase activity observed either after a single insult of 2 min or 10 min ischemia. We suggest that the maintenance of Na+,K+-ATPase activity afforded by preconditioning be related to cellular neuroprotection. 相似文献
18.
Om Prakash Mishra Maria Delivoria-Papadopoulos Geraldine Cahillane L. Craig Wagerle 《Neurochemical research》1989,14(9):845-851
The effect of lipid peroxidation on the affinity of specific active sites of Na+, K+-ATPase for ATP (substrate), K+ and Na+ (activators), and strophanthidin (a specific inhibitor) was investigated. Brain cell membranes were peroxidized in vitro in the presence of 100M ascorbate and 25M FeCl2 at 37°C for time intervals from 0–20 min. The level of thiobarbituric acid reactive substances and the activity of Na+, K+-ATPase were determined. The enzyme activity decreased by 80% in the first min. from 42.0±3.8 to 8.8±0.9 mol Pi/mg protein/hr and remained unchanged thereafter. Lipid peroxidation products increased to a steady state level from 0.2±0.1 to 16.5 ±1.5 nmol malonaldehyde/mg protein by 3 min. In peroxidized membranes, the affinity for ATP and strophanthidin was increased (two and seven fold, respectively), whereas affinity for K+ and Na+ was decreased (to one tenth and one seventh of control values, respectively). Changes in the affinity of active sites will affect the phosphorylation and dephosphorylation mechanisms of Na+, K+-ATPase reaction. The increased affinity for ATP favors the phosphorylation of the enzyme at low ATP concentrations whereas, the decreased affinity for K+ will not favor the dephosphorylation of the enzyme-P complex resulting in unavailability of energy for transmembrane transport processes. The results demonstrate that lipid peroxidation alters Na+, K+-ATPase function by modification at specific active sites in a selective manner, rather than through a non-specific destructive process. 相似文献
19.
Rat C6 glioma cells were cultured for 4 days in MEM medium supplemented with 10% bovine serum and Na+,K+-ATPase activity was determined in homogenates of harvested cells. Approximately 50% of enzyme activity was attained at 1.5 mM K+ and the maximum (2.76±0.13 mol Pi/h/mg protein) at 5 mM K+. The specific activity of Na+,K+-ATPase was not influenced by freezing the homogenates or cell suspensions before the enzyme assay. Ten minutes' exposure of glioma cells to 10–4 or 10–5 M noradrenaline (NA) remained without any effect on NA+,K+-ATPase activity. Neither did the presence of NA in the incubation medium, during the enzyme assay, influence the enzyme activity. The nonresponsiveness of Na+,K+-ATPase of C6 glioma cells to NA is consistent with the assumption that (+) form of the enzyme may be preferentially sensitive to noradrenaline. Na+,K+-ATPase was inhibited in a dose-dependent manner by vanadate and 50% inhibition was achieved at 2×10–7 M concentration. In spite of the fact that Na+,K+-ATPase of glioma cells was not responsive to NA, the latter could at least partially reverse vanadate-induced inhibition of the enzyme. Although the present results concern transformed glial cells, they suggest the possibility that inhibition of glial Na+,K+-ATPase may contribute to the previously reported inhibition by vanadate of Na+,K+-ATPase of the whole brain tissue. 相似文献
20.
Na+,K+-ATPase activity was determined in fetal guinea pig brain at 35, 40, 45, 50, 55, and 60 days of gestation. The activity remained at a constant level during the early periods (35–45 days) of gestation and increased significantly during 45–60 days. Following maternal hypoxia, the activity of Na+,K+-ATPase in the term (60 days) fetal brain was reduced by 50% whereas the preterm (50 days) brain activity was unaffected. Under identical hypoxic conditions, the enzymatic activity of adult brain was significantly reduced by 20%. Na+,K+-ATPase obtained from fetal brain (50 days of gestation) has both a low and a high affinity for ATP (K
m values =0.50 and 0.053 mM and correspondingV
max values =10.77 and 2.82 umoles Pi/mg protein/hr), whereas the enzyme in the adult brain has only a low affinity (K
m=1.67 mM andV
max=20.32 umoles Pi/mg protein/hr). The high and low affinity sites for ATP in the fetal brain suggests a mechanism essential for the maintenance of cellular ionic gradients at low concentrations of ATP and which would provide the fetal brain with a greater tolerance to hypoxia. The high sensitivity of Na+,K+-ATPase activity to hypoxia in guinea pig brain at term suggests that the cell membrane functions of the fetal brain may be more susceptible to hypoxia at term than it is earlier in gestation. 相似文献