Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leishmania major promastigotes maintain a relatively high pool of free amino acids (> 100 mM) under in vitro growth conditions. They also maintain a hyperpolarized plasma membrane which is primarily set by a dicyclohexylcarbodiimide (DCCD)-sensitive electrogenic H(+)-pump. We studied here the possible contribution of the membrane potential (Vm) and the transmembrane proton gradient (delta pH) to the mediated uptake of amino acids and their intracellular accumulation. Proline transport and accumulation were assessed by analysis of time-dependent changes in the internal pools of free amino acids and by uptake of radiolabelled proline. Proline uptake was markedly affected by changes in the Vm and considerably less by changes in delta pH. The most pronounced effects were obtained by treatment with either the H(+)-uncoupler carbonylcyanide chlorophenylhydrazone (CCCP), the cation ionophore gramicidin or by omitting Cl- from the medium (by exchange with gluconate or mannitol). Relatively smaller effects were obtained in the presence of the H(+)-ATPase inhibitor DCCD or with the anion transport blocker 4,4'-diisothiocyanodihydrostilbene-2,2'-disulfonic acid (H2DIDS). No significant effects were found with cells exposed to K+ in the presence of nigericin, to Na+ in the presence of monensin or to other cations substituting for Na+. These results suggest that neither extracellular Na+ or K+, per se, nor even intracellular pH, play a major role in proline uptake and accumulation. A significant stimulation in proline uptake induced by HCO3- could be associated with membrane hyperpolarization or intracellular alkalinization. The present observations indicate that uphill nutrient uptake by Leishmania promastigotes is largely determined by Vm. The relatively high intracellular pools of amino acids might be of physiological relevance to osmoregulation by parasites.
Mol Biochem Parasitol 1995 Dec
PMID:Amino acid uptake and intracellular accumulation in Leishmania major promastigotes are largely determined by an H(+)-pump generated membrane potential. 872 Jan 71

Rabbit, pigeon and rat liver mitochondria convert exogenous phosphoenolpyruvate and acetylcarnitine to citrate at rates of 14, 74 and 8 nmol/15 min/mg protein. Citrate formation is dependent on exogenous HCO3-, is increased consistently by exogenous nucleotides (GDP, IDP, GTP, ADP, ATP) and inhibited strongly by 3-mercaptopicolinate and 1,2,3-benzenetricarboxylate. Citrate is not made from pyruvate alone or combined with acetylcarnitine. Pigeon and rat liver mitochondria make large amounts of citrate from exogenous succinate, suggesting the presence of an endogenous source of acetyl units or means of converting oxalacetate to acetyl units. Citrate synthesis from succinate by pigeon and rabbit mitochondria is increased significantly by exogenous acetylcarnitine. Pigeon and rat liver contain 80 and 15 times, respectively, more ATP:citrate lyase activity than does rabbit liver. Data suggest that mitochondrial phosphoenolpyruvate carboxykinase in vivo could convert glycolysis-derived phosphoenolpyruvate to oxalacetate that, with acetyl CoA, could form citrate for export to support cytosolic lipogenesis as an activator of acetyl CoA carboxylase, a carbon source via ATP:citrate lyase and NADPH via NADP:malate dehydrogenase or NADP:isocitrate dehydrogenase.
Comp Biochem Physiol B Biochem Mol Biol 1996 Aug
PMID:Synthesis of citrate from phosphoenolpyruvate and acetylcarnitine by mitochondria from rabbit, pigeon and rat liver: implications for lipogenesis. 884 May 17

RINm5F insulinoma cells show a defective physiological insulin secretory response to glucose stimulation. The short chain carbonic acid sodium butyrate induced a growth arrest during a 72-h tissue culture period. In contrast to control RINm5F cells, 2 mM glucose increased insulin secretion by more than 70% in these sodium butyrate-treated cells (1 mM) without any further increase of the secretory rate between 2 and 20 mM glucose. This effect of sodium butyrate on insulin secretion was assessed in comparison with its effect on gene expression of the GLUT1 and GLUT2 glucose transporter, hexokinase type I and type II, glucokinase and insulin. Sodium butyrate at a 1 mM concentration decreased GLUT1 gene expression by nearly 50%, but did not induce gene expression of the low-affinity GLUT2 glucose transporter above the detection limit. Furthermore, sodium butyrate increased glucokinase gene expression by more than 50% and hexokinase type II gene expression by more than 100%, while insulin gene expression was increased only by 24%. Hexokinase type II enzyme activity was increased by more than 100% without a concomitant significant change of the glucokinase enzyme activity. Sodium butyrate (2 mM) caused effects comparable with those of 1 mM sodium butyrate. Thus the improved insulin secretory responsiveness of RINm5F insulinoma cells after sodium butyrate treatment at low non-physiological millimolar glucose concentrations can be interpreted as a result of an increased hexokinase-mediated metabolic flux rate through the glycolytic chain.
J Mol Endocrinol 1996 Aug
PMID:Effects of sodium butyrate on glucose transporter and glucose-phosphorylating enzyme gene expression in RINm5F insulinoma cells. 886 83

Bicarbonate/CO2 is believed to be the key in vitro effector of sperm capacitation, a process which induces major changes in the sperm plasma membrane in preparation for fertilization. In a flow cytometric study, we examined the effect of bicarbonate on boar spermatozoa using merocyanine, an impermeant lipophilic probe which binds to plasma membranes with increasing affinity as their lipid components become more disordered. We found that bicarbonate causes a rapid increase in the ability of live boar spermatozoa to bind merocyanine. First detected about 100 sec after exposure to bicarbonate and largely complete by 300 sec, this increase appears to result from individual cells within the sperm population switching from a low merocyanine-binding state to a high binding state. The majority of live spermatozoa are capable of responding in this way, and do so in proportion to bicarbonate concentration, half-maximal response being induced by about 3 mM bicarbonate; however, overall population response varies greatly between ejaculates. Increased merocyanine stainability is observed over the whole surface area of the cell, and is reversible both with respect to temperature (it is only manifested above 30 degrees C) and with respect to presence of bicarbonate. A similar effect can be induced by phosphodiesterase inhibitors such as isobutylmethylxanthine, and enhanced by a permeant cyclic nucleotide analogue. We conclude that bicarbonate causes a major alteration in sperm plasma membrane lipid architecture, apparently by perturbing enzymic control processes. This novel action of bicarbonate may represent an initial permissive event in the capacitation sequence.
Mol Reprod Dev 1996 Nov
PMID:Bicarbonate/CO2, an effector of capacitation, induces a rapid and reversible change in the lipid architecture of boar sperm plasma membranes. 891 50

SSM4 was isolated as a suppressor of rna14-1, a mutant involved in nuclear mRNA maturation. In order to isolate genes interacting with SSM4, we have searched for mutants that are syntheticlethal in association with an SSM4 deletion. Among the mutants obtained, one, named sls1-1, shows a pet- phenotype. We have cloned and sequenced this gene. It encodes a protein with a calculated molecular mass of 73 kDa. This protein contains a mitochondrial targeting presequence but does not show homology with other known proteins. Deletion of SLS1 does not affect cell viability on glucose but is lethal on a non-fermentable medium. The Sls1p protein does not appear to be involved in mitochondrial DNA replication, transcription, or in RNA splicing maturation or stability. We have also tagged this protein and localized it in mitochondria. Treatment with alkaline carbonate does not extract this protein from mitochondria, suggesting strongly that it is a mitochondrial integral membrane protein. Thus, the SLS1 gene, encodes a mitochondrial integral membrane protein and is paradoxically synlethal in association with a deletion of the SSM4 gene, which encodes an integral nuclear membrane protein.
Mol Gen Genet 1996 Oct 28
PMID:SLS1, a new Saccharomyces cerevisiae gene involved in mitochondrial metabolism, isolated as a syntheticlethal in association with an SSM4 deletion. 891 13

Band 3 protein is a typical polytropic membrane protein and mediates the exchange of the cellular HCO3- with CI- in plasma, which has been known as the "Chloride Shift". Owing to the "Chloride Shift", red blood cells can discriminate the metabolically active cells from inactive cells and deliver oxygen particularly to metabolically active tissues that produce carbon dioxide. Thus, band 3 protein is a sensor for metabolically active tissues and no excess oxygen is supplied to tissues as far as oxygen is delivered by red blood cells. In this chapter, we review the physiological role of the anion exchange mediated by band 3 protein and our work concerning the structure and function relationship in band 3 protein, that, is, affinity labeling of the active center for the anion exchange with pyridoxal phosphate, conformational change during the anion exchange process, examination of fidelity of hydropathy prediction on band 3 protein, and phosphoenolpyruvate transport mediated by band 3 protein and its clinical application.
Cell Mol Biol (Noisy-le-grand) 1996 Nov
PMID:Band 3 protein: physiology, function and structure. 896 Jul 78

The interaction between Na+ and H+ ions upon Na-H exchange (NHE) was examined in sheep cardiac Purkinje fibers. Acid equivalent fluxes through NHE were examined using recordings of intracellular pH and Na+ in isolated preparations measured with ion selective microelectrodes. The extent of acid-extrusion by NHE was estimated from pH(i) recovery-rate, multiplied by beta(i) (intracellular buffering power) in response to an internal acid load induced by 20 mm NH4Cl removal (nominally HCO3- free media). A mixed inhibitory effect was found of extracellular H+ on external Na+-activation of NHE (i.e. an increase, at low pH(o), in the apparent Michaelis constant for external Na+ ions [K(Nao)(0.5)] and a decrease in the maximum transport rate [V(Nao)(max)]). In addition, we confirmed that the stoichiometry of Na(o) binding is unaffected by the pH(o) (between 7.5 and 6.5), showing a Hill coefficient close to one. The interaction between Na+ and H+ ions at the internal face of the cardiac NHE was also studied. Our evidence suggests that an increase in the intracellular Na+ ion concentration ([Na+]i) inhibits acid efflux and that this inhibition can be approximated by the decrease in thermodynamic driving force caused by reducing the transmembrane Na+ gradient. It appears, however, that small variations in [Na+]i from the normal resting level (intracellular sodium activity, a(i)Na = 7 to 13 mm) have little or no effect on acid efflux, suggesting that variation of a(i)Na is not a physiologically important controller of NHE activity in heart.
J Mol Cell Cardiol 1997 Apr
PMID:Interaction between Na+ and H+ ions on Na-H exchange in sheep cardiac Purkinje fibers. 916 Aug 65

To investigate the role of Na(+)-H+ exchange occurring during hypoxia in the genesis of reoxygenation-induced myocardial oedema, isolated perfused rat hearts were submitted to 40 min of hypoxia and 90 min of reoxygenation. The influence of three factors on myocardial water content was analysed according to a 2 x 2 x 2 factorial design; the hearts were perfused at either pH = 7.4 or pH = 7.0, with either HCO3- buffer or HCO3(-)-free HEPES buffer, and in half of the experiments the hypoxic buffer contained HOE642 6.7 micromol/l. In an additional group, 160 min of normoxia resulted in no lactate dehydrogenase (LDH) release and in a 35.8% increase in myocardial water, independently of pH and of the presence of HCO3- in the buffer. In hearts perfused at pH = 7.4, reoxygenation induced LDH release which was reduced (P<0.05) by HOE642 by 20.1%, by HCO3(-)-free perfusion by 57.5%, and by the combination of both by 91.2%. Reoxygenation also induced severe myocardial oedema (26.3% increase (P<0.05) respect to normoxia). HOE642 reduced (P<0.05) reoxygenation oedema by 15.7%, HCO3(-)-free perfusion by 8.9%, and the combination of both by 24.6%. The effects of HCO3(-)-free perfusion could be mimicked in HCO3(-)-perfused hearts by blocking Na(+)-HCO3- cotransport with 4-4'-dibenzanidostilbene-2,2'-disulphonic acid (DIDS). The beneficial and additive effects of HOE642 and of HCO3(-)-free perfusion on oedema were not a mere consequence of their protective effects against the oxygen paradox, since they were observed in groups perfused at pH= 7.0, a condition which virtually prevented LDH release without preventing oedema (19.0% increase in myocardial water). Thus, reoxygenation-induced myocardial oedema may occur in the absence of necrosis, and is largely determined by Na+ gain during hypoxia via Na(+)-H+ exchange and Na(+)-HCO3- cotransport.
J Mol Cell Cardiol 1997 Apr
PMID:The role of Na+-H+ exchange occurring during hypoxia in the genesis of reoxygenation-induced myocardial oedema. 916 Aug 68

Reduction of extracellular pH (pHo) leads to a fall of intracellular pH (pHi) in the guinea-pig ventricular myocyte. In nominally CO2/HCO3--free conditions, this has been attributed to stimulation of OH- ion efflux on a novel Cl--OH- exchange carrier in the sarcolemma. In the present work, we have tested for the possible participation of bicarbonate ions. Residual bicarbonate levels may occur through hydration of CO2 arising either from cellular metabolism or from the atmosphere. The pHi was measured by using the intracellular pH-fluorophore, carboxy SNARF-1 (AM-loaded). Possible sources of CO2 were eliminated by adding the aerobic inhibitors, cyanide or rotenone, and by equilibrating the superfusates flowing over the myocyte with a CO2-free, 100% N2 atmosphere. The fall of pHi upon reducing pHo (to 6.4) persisted after complete CO2-removal. This indicates that, in nominally CO2-free conditions, residual HCO3- transport on a Cl--HCO3- exchanger cannot account for the pHo-dependence of pHi, and supports the hypothesis for a Cl--OH- exchanger (or, alternatively, an H+-Cl- co-influx mechanism).
J Mol Cell Cardiol 1997 Sep
PMID:Chloride-hydroxyl exchange in the guinea-pig ventricular myocyte: no role for bicarbonate. 929 71

Enterocytes from fasted rabbits make glucose from exogenous fructose and dihydroxyacetone at rates of 180 and 91 nmol/min/10(8) cells but do not make glucose from glycerol, aspartate, malate, lactate, alpha-ketoglutarate, glutamate or glutamine. Total activities of phosphoenolpyruvate carboxykinase, fructose 1,6-bisphosphatase and glucose 6-phosphatase in isolated enterocytes are 0.44, 0.60 and 1.90 mumol/min/10(8) cells, and > or = 95% of carboxykinase activity is intramitochondrial. Enterocytes contain marginal glycerol kinase (0.05 mumol/ min/10(8) cells) and essentially no pyruvate carboxylase activities. Enterocyte mitochondria synthesize citrate from exogenous phosphoenolpyruvate and acetylcarnitine at a rate of 2.40 nmol/min/mg protein. Citrate formation is highly dependent on exogenous HCO3 and inhibited strongly by 3-mercaptopicolinate and 1,2,3-benzenetricarboxylate. Citrate synthesis is stimulated consistently by GDP and significantly so by GTP. Citrate production is unaffected by ADP or ATP. Enterocytes from fasted-refed rabbits contain activities of 0.05, 0.12, 0.39 and 0.56 mumol/min/mg cytosolic protein of ATP:citrate lyase, NADP:malate dehydrogenase, glucose 6-phosphate dehydrogenase and NADP:isocitrate dehydrogenase. Activities of NADP:malate dehydrogenase, glucose 6-phosphate dehydrogenase and NADP:isocitrate dehydrogenase are significantly higher in enterocytes from fasted-refed rabbits than those from fasted rabbits. Mitochondrial phosphoenolpyruvate carboxykinase in enterocytes in vivo could convert glycolysis-derived phosphoenolpyruvate to oxaloacetate that, with acetyl CoA, could form citrate for export to support cytosolic lipogenesis as an activator of acetyl CoA carboxylase, a source of carbon via ATP:citrate lyase and of NADPH via NADP:malate dehydrogenase or NADP:isocitrate dehydrogenase.
Comp Biochem Physiol B Biochem Mol Biol 1997 Nov
PMID:Synthesis of citrate from phosphoenolpyruvate and acetylcarnitine by mitochondria from rabbit enterocytes: implications for lipogenesis. 946 72


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>