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Biomedical subjects

A Askari

Publications and source records attributed to A Askari.

At least 73 records · Page 4Linked to original sources
PubMed1988

The influence of ketosis on the metabolic response to skeletal trauma.

Intravenous glucose and ketone body feeding were compared for their potential in altering urinary nitrogen losses by the traumatized rat. Eighteen male rats were traumatized by bilateral femoral fracture. The rats were fed totally by vein for 3 days prior and 3 days after injury and the infusion rate was held constant over the 6 days of infusion. Group GT rats were fed glucose as the source of nonprotein energy while group MT rats were fed a mixture of 72% monoacetoacetin (the monoglyceride of acetoacetate)-28% glucose for the nonprotein energy. Total urinary nitrogen excretion on a 24-hr basis was measured for each of the 6 days of intravenous feeding. On the third day post-trauma, each rat was evaluated for leucine kinetics using a continuous infusion of L-[1-14C]leucine and measurement of breath and plasma specific activities. Rats from group MT were hyperketonemic and normoglycemic and rats from group GT were normoketonemic and hyperglycemic. Urinary nitrogen losses, leucine oxidation, and leucine turnover were similar for the two groups. We conclude that ketone bodies are as good an intravenous source of energy as is glucose, and the ketone bodies do not cause hyperglycemia.

Acetoacetates↗
PubMed1988

Sarcoidosis: atypical presentation associated with features of systemic lupus erythematosus.

A 52-year-old woman presented with rash, bilateral uveitis and polyarthritis of her hands. Laboratory tests were consistent with the diagnosis of systemic lupus erythematosus (SLE). Ten years later she developed dyspnea associated with bihilar lymphadenopathy. Lung function tests showed a restrictive pattern and bronchial biopsy revealed the presence of noncaseating granulomata. We report this rare concomitant appearance of SLE and sarcoidosis.

Antibodies, Antinuclear↗
PubMed1987

Control of cardiac sodium pump by long-chain acyl coenzymes A.

Since we had shown recently that fatty acyl-CoA derivatives stimulate (Na+ + K+)-ATPase activity at suboptimal ATP concentrations, we used sealed vesicles of beef heart sarcolemma to examine the effects of these compounds on the transport function of the enzyme. The sodium pump was detected in inside-out vesicles as a component of Na+ uptake that was dependent on intravesicular (extracellular) K+ and extravesicular (intracellular) ATP and was sensitive to vanadate and digitoxigenin. The pump flux was stimulated without a lag by palmitoyl-CoA (K0.5 = 3 microM) when ATP concentration was 50 microM, but not when it was 2 mM. Saturating palmitoyl-CoA reduced the K0.5 of ATP for the pump by a factor of 3-6. Raising the intracellular K+ concentration increased the K0.5 of ATP, and this effect of K+ was antagonized by palmitoyl-CoA. At concentrations up to 0.5 mM, palmitoyl-CoA had no effect on ATP-independent (passive) Na+ uptake. All tested long-chain acyl-CoA derivatives had effects similar to that of palmitoyl-CoA; but CoA, acetyl-CoA, and palmitic acid were ineffective. Palmitoyl carnitine and docosahexanoic acid, amphiphilic compounds with inhibitory and biphasic effects on the hydrolytic activity of purified (Na+ + K+)-ATPase, had purely inhibitory effects on the pump at high concentrations that also affected the passive fluxes. The data support the proposition that fatty acyl-CoA derivatives mimic the effect of ATP at a regulatory site and suggest that these intracellular liponucleotides may be involved in the control of the pump.

Acyl Coenzyme A↗
PubMed1987

(Na+ + K+)-ATPase: on the number of the ATP sites of the functional unit.

Questions concerning the number of the ATP sites of the functional unit of (Na+ + K+)-ATPase (i.e., the sodium pump) have been at the center of the controversies on the mechanisms of the catalytic and transport functions of the enzyme. When the available data pertaining to the number of these sites are examined without any assumptions regarding the reaction mechanism, it is evident that although some relevant observations may be explained either by a single site or by multiple ATP sites, the remaining data dictate the existence of multiple sites on the functional unit. Also, while from much of the data it is clear that the multiple sites of the unit enzyme represent the interacting catalytic sites of an oligomer, it is not possible to rule out the existence of a distinct regulatory site for ATP in addition to the interacting catalytic sites. Regardless of the ultimate fate of the regulatory site, any realistic approach to the resolution of the kinetic mechanism of the sodium pump should include the consideration of the established site-site interactions of the oligomer.

Adenosine Triphosphate↗
PubMed1986

Total parenteral feeding of rats with an acetoacetate monoglyceride and glucose mixture.

Total parenteral nutrition (TPN) by means of monoacetoacetin (glycerol monoacetoacetate) was compared with TPN by using glucose-glycerol. Growth and urinary nitrogen, copper and zinc over 7 d and leucine dynamics on the last day were studied. Complete intravenous diets were administered to five groups of rats which were differentiated by receiving 45 kcal/d (group A) or 65 kcal/d (group C) from a 50% glucose-50% glycerol mixture, 45 kcal/d (group B) or 65 kcal/d (group D) from a 67% monoacetoacetin-33% glucose mixture, or 45 kcal/d (group E) from 100% monoacetoacetin. Leucine kinetics were determined by continuous infusion. Animals from groups A and C were hyperglycemic and normoketonemic, groups B and D were normoglycemic and hyperketonemic, and group E tended to be normoglycemic and hyperketonemic. Group B rats gained weight and retained the most nitrogen while groups A and E lost weight and groups C and D maintained their weight. Nitrogen losses correlated with weight changes. Urinary copper and zinc were not increased by giving ketone bodies. Leucine kinetics were found to be low for group C compared to its energy-matched group, and leucine metabolism was not correlated with nitrogen output and growth. The data suggest that a monoacetoacetin-glucose mixture is preferable as a nonprotein energy source for TPN when compared to either substance alone.

Animals↗
PubMed1986

Activation of (Na++K+)-ATPase by long-chain fatty acids and fatty acyl coenzymes A.

Long-chain unsaturated fatty acids and fatty acyl CoA derivatives activated (Na++K+)-ATPase at suboptimal, but not optimal, ATP concentrations. Activation was obtained within a narrow range of fatty acid concentrations; higher acid levels inhibited the enzyme. The various CoA esters, however, activated with K0.5 values in the range of 0.15-10 microM; and with no inhibitory effects at concentrations up to 100 microM. Palmitoyl CoA, binding reversibly to a regulatory site, reduced K0.5 of ATP from 0.37 mM to 0.17 mM; and changed the Hill coefficient of the substrate-velocity curve from 0.86 to 0.63. These compounds may be physiological regulators that desensitize the function of this enzyme to diminishing ATP levels.

Acyl Coenzyme A↗
PubMed1985

Mechanisms of detergent effects on membrane-bound (Na+ + K+)-ATPase.

Because the nonionic detergent octaethylene glycol dodecyl ether has been used extensively for studies on active solubilized preparations of (Na+ + K+)-ATPase, we tried to see if the detergent alters the properties of the membrane-bound enzyme prior to solubilization. Addition of the detergent, at concentrations below its critical micellar concentration, to reaction mixtures containing the highly purified membrane-bound enzyme reduced the K0.5 of ATP for (Na+ + K+)-dependent ATPase activity without affecting the maximal velocity or abolishing the negative cooperativity of the substrate-velocity curve. Under these conditions, however, the enzyme was not solubilized as evidenced by complete sedimentation of the membrane fragments containing the enzyme upon centrifugation at 100,000 X g for 30 min. Other nonsolubilizing effects of the detergent included an increase in K0.5 of K+, inhibition of Na+-dependent ATPase with no effect on K0.5 of ATP for this activity, and reductions in the spontaneous decomposition rates of the K+-sensitive phosphoenzyme obtained from ATP and the phosphoenzyme obtained from Pi. The nonsolubilizing effects of the detergent on the purified enzyme were obtained with no detectable lag, were readily reversible, and could be distinguished from its vesicle-opening effects on crude membrane preparations. Several other nonionic and ionic detergents had similar effects on the enzyme. The findings indicate (a) detergent binding to hydrophobic sites on extramembranous segments of enzyme subunits; (b) that occupation of these sites mimics the effects of ATP at a low-affinity regulatory site with no effect on high-affinity ATP binding to the catalytic site; and (c) that in studies on detergent-solubilized preparations, it is necessary to distinguish between the effects of solubilization per se and detergent effects at the regulatory site.

Animals↗
PubMed1985

Coexistence of two ATP sites on the ouabain-complexed (Na+ + K+)-ATPase.

When the effects of varying concentrations of ATP on the dissociation rate of the ouabain-enzyme complex were studied, the dissociation rate constant increased with increasing ATP concentrations up to 1 mM, and then decreased with further rise in ATP; indicating that ATP binds to two distinct sites on the complex. ADP and AMP-PNP had similar biphasic effects. GTP, CTP, UTP, and AMP-PCP reduced the dissociation rate. AMP and Pi had no effects. Increase in dissociation rate caused by 0.5 mM ATP was not abolished by saturating CTP, indicating the binding of CTP to only one of the two ATP sites. The data suggest the existence of separate catalytic and regulatory sites, with different affinities and nucleotide specificities.

Adenosine Triphosphate↗
PubMed1984

Simultaneous bindings of ATP and vanadate to (Na+ + K+)-ATPase. Implications for the reaction mechanism of the enzyme.

Inhibition of (Na+ + K+)-dependent adenosine triphosphatase phosphatase by vanadate is thought to occur through the tight binding of vanadate to the same site from which Pi is released. To see if ATP binds to [48V] vanadate-enzyme complex, just as it does to the phosphoenzyme, the effects of Na+, K+, and ATP on the dissociation rate of the complex at 10 degrees C were studied. The rate constant was increased by Na+, and this increase was blocked by K+, indicating that either Na+ or K+ binds to the complex. ATP alone, or in combination with K+, had no effect on the rate constant. In the presence of Na+, however, ATP caused a further increase in the rate constant. The value of K0.5 of Na+ was the same in the presence or absence of ATP; K0.5 of ATP (0.2 mM) did not seem to change significantly when Na+ concentration was varied, and K0.5 of K+, at a constant Na+ concentration, was the same in the presence or absence of ATP. The data indicate that ATP binds to the enzyme-vanadate complex regardless of the presence or absence of Na+ or K+, but it affects the dissociation rate only when Na+ is bound simultaneously. The value of K0.5 of Na+ decreased as pH was increased in the range of 6.5-7.8, but K0.5 of ATP was independent of pH. Demonstration of ATP binding to the enzyme-vanadate complex provides further support for the suggestion that the oligomeric enzyme contains a low-affinity regulatory site for ATP that is distinct from the interacting high-affinity catalytic sites.

Adenosine Triphosphate↗
PubMed1984

Regulation of (Na++K+)-ATPase by inorganic phosphate: pH dependence and physiological implications.

Inhibition of Na++K+-dependent ATPase activity by Pi was maximal in the pH range of 6.1-7, but decreased with increasing pH in the range of 7-8.5. Ki of Pi was 2.8 mM at pH 7.1, and 12 mM at pH 7.8. K+-dependent phosphorylation of the enzyme by Pi, which is thought to be responsible for inhibition of ATPase activity, also decreased with increasing pH. The data suggest that (a) previously observed requirement of high Pi concentrations for inhibition of ATPase activity and associated pump fluxes may have been due to high pH of the assays; (b) at normal values of intracellular pH the pump may be partially inhibited by intracellular Pi; and (c) this effect of Pi may be amplified or dampened with alterations in intracellular pH and ATP/Pi ratio.

Adenosine Triphosphate↗
PubMed1984

Reaction of (Na+ + K+)-dependent adenosine triphosphatase with inorganic phosphate. Regulation by Na+, K+, and nucleotides.

Effects of Na+, K+, and nucleotides on Mg2+-dependent phosphorylation of (Na+ + K+)-dependent adenosine triphosphatase by Pi were studied under equilibrium conditions. Na+ was a linear competitive inhibitor with respect to Mg2+ and a mixed inhibitor with respect to Pi. K+ was a partial inhibitor; it interacted with positive cooperativity and induced negative cooperativities in the interactions of Mg2+ and Pi with the enzyme. Adenyl-5'-yl (beta, gamma-methylene)diphosphonate, a nonhydrolyzable analog of ATP, interacted with negative cooperativity to inhibit phosphorylation in competition with Pi. ATP was also a competitive inhibitor. Na+ and K+ acted antagonistically, Na+ and nucleotides inhibited synergistically, and K+ and nucleotides were mutually exclusive. In the presence of ouabain, when nucleotides were excluded from the site inhibiting phosphorylation, a low affinity regulatory site for nucleotides became apparent, the occupation of which reduced the rate of dephosphorylation and the initial rate of phosphorylation of the enzyme without affecting the equilibrium constant of the reaction of Pi with the ouabain-complexed enzyme. The regulatory site was also detected in the absence of ouabain. The data suggest that catalytic and transport functions of the oligomeric enzyme may be regulated by homotropic and heterotropic site-site interactions, ligand-induced slow isomerizations, and distinct catalytic and regulatory sites for ATP.

Adenosine Triphosphate↗
PubMed1984

Evidence for heterogeneity in hereditary hemochromatosis. Evaluation of 174 persons in nine families.

Hereditary hemochromatosis is an autosomal recessive disease in which the gene is linked to the HLA system. Investigation of nine unrelated probands and their family members has revealed distinct groups based on biochemical and clinical manifestations of the disease. Four different types of disease expression were identified: Group I--classic hereditary hemochromatosis with elevated transferrin saturation, serum ferritin levels, and liver iron content; Group II--severe iron overload, accelerated disease manifesting at an early age; Group III--elevated total body iron stores, normal transferrin saturation and serum ferritin levels; Group IV--markedly elevated findings on serum biochemical tests, e.g., transferrin saturation, serum ferritin levels, with minimal elevation in total body iron stores. This evidence for several clearly distinguishable modes of expression in different families suggests that more than one genetic lesion in iron metabolism may be responsible for iron overload in hereditary hemochromatosis. This genetic heterogeneity may be helpful in delineating the fundamental abnormalities in iron metabolism in this group of disorders.

Absorption↗
PubMed1984

Interaction of Ca2+ with (Na+ + K+)-ATPase: properties of the Ca2+-stimulated phosphatase activity.

Ca2+ inhibited the Mg2+-dependent and K+-stimulated p-nitrophenylphosphatase activity of a highly purified preparation of dog kidney (Na+ + K+)-ATPase. In the absence of K+, however, a Mg2+-dependent and Ca2+-stimulated phosphatase was observed, the maximal velocity of which, at pH 7.2, was about 20% of that of the K+-stimulated phosphatase. The Ca2+-stimulated phosphatase, like the K+-stimulated activity, was inhibited by either ouabain or Na+ or ATP. Ouabain sensitivity was decreased with increase in Ca2+, but the K0.5 values of the inhibitory effects of Na+ and ATP were independent of Ca2+ concentration. Optimal pH was 7.0 for Ca2+-stimulated activity, and 7.8-8.2 for the K+-stimulated activity. The ratio of the two activities was the same in several enzyme preparations in different states of purity. The data indicate that (a) Ca2+-stimulated phosphatase is catalyzed by (Na+ + K+)-ATPase; (b) there is a site of Ca2+ action different from the site at which Ca2+ inhibits in competition with Mg2+; and (c) Ca2+ stimulation can not be explained easily by the action of Ca2+ at either the Na+ site or the K+ site.

4-Nitrophenylphosphatase↗
PubMed1983

Subunit associations of (Na+ + K+)-dependent adenosine triphosphatase. Chemical cross-linking studies.

Cross-linking reactions of the alpha- and beta-subunits of the purified membrane-bound enzyme with several reagents were studied. In the presence of 1,5-difluoro-2,4-dinitrobenzene, formation of a cross-linked alpha, beta-dimer was affected specifically by K+ + ATP or enzyme phosphorylation. The same conditions affected the formation of cross-linked alpha, alpha-dimer in the presence of 4,4'-difluoro-3,3'-dinitrodiphenyl sulfone or o-phenanthroline-Cu2+. Since noncovalent alpha, beta-association has been established, the data suggest K+ + ATP-induced or phosphorylation-induced changes in alpha, beta-domain and alpha, alpha-domain of an oligomer of alpha, beta-dimer. When the formation of cross-linked alpha, beta-dimer or alpha, alpha-dimer was induced by phosphorylation, only half of the subunits were cross-linked, suggesting the existence of a cooperative tetramer of alpha, beta-dimer. When microsomes or red cell membranes were exposed to 32Pi under phosphorylation-induced cross-linking conditions, the only products were alpha, beta-dimer and alpha, alpha-dimer, indicating the existence of an oligomer of alpha, beta-dimer in crude membranes. Subunits of the enzyme solubilized with octaethylene glycol dodecyl ether, by methods that have been suggested to yield unassociated alpha, beta-dimers, underwent spontaneous cross-linking that was not affected by enzyme dilution. Since the largest product was alpha 2 beta 2, the solubilized enzyme is at least a dimer of alpha, beta-dimer. The findings establish that the membrane-bound enzyme is an oligomer of alpha, beta-dimer. Whether or not a single alpha, beta-dimer is capable of catalytic and transport functions has not been determined.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗