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Biomedical subjects

R Whittam

Publications and source records attributed to R Whittam.

At least 37 records · Page 2Linked to original sources
PubMed1970

The coupling of downhill ion movements associated with reversal of the sodium pump in human red cells.

1. Previous work on the incorporation of inorganic phosphate (P(i)) into ATP has suggested reversal of the chemical reactions of the Na pump in human red cells. A study has now been made of the associated movements of Na and K.2. The efflux of K, and the influx and efflux of Na were measured. When the Ringer was without K, the loss of cell K was inhibited by ouabain, and the ouabain-sensitive component of K efflux (0.36 mu-equiv.ml.(-1).hr(-1)) required external Na.3. The exchange of Na was also inhibited by ouabain. When influx and efflux of Na were measured simultaneously in K-free Ringer there was an excess of ouabain-sensitive influx over efflux of about 0.36 mu-equiv.ml.(-1).hr(-1). This difference balanced the ouabain-sensitive K efflux, and was not found with 10 mM-external K. The Na and K movements appear to be coupled and to be mediated by reversal of the Na pump.4. The net uptake of Na sensitive to ouabain was 0.38 mu-equiv.ml.(-1).hr(-1) for red cells incubated in K-free Ringer, and the net loss of K under the same conditions was 0.58 mu-equiv.ml.(-1).hr(-1) in rough keeping with the unidirectional flux values.5. Oligomycin decreased Na influx and efflux to the same extent as ouabain.6. There appears to be a coupled downhill movement of Na and K that is abolished both by inhibitors of the Na pump and by external K which promotes normal transport of Na outwards and K inwards.

Biological Transport, Active↗
PubMed1970

The involvement of phosphatidylserine in adenosine triphosphatase activity of the sodium pump.

1. A study has been made to see whether the ATPase of the Na pump is activated by phospholipids.2. Solubilization of a membrane-containing (microsomal) fraction from ox brain cortex with deoxycholate removed most or all of the ouabain-inhibited ATPase and p-nitrophenylphosphatase (pNPPase) activities. Addition of sonicated dispersions of crude commercial samples of phosphatidic acid, phosphatidylinositol or phosphatidylserine stimulated both enzymic activities, but neither phosphatidylcholine nor phosphatidylethanolamine affected them. After partial purification by chromatography, however, definite activation was demonstrated only with that component of crude samples which migrated like phosphatidylserine.3. The ATPase activity dependent on phosphatidylserine was eliminated by removal of Na and K or by addition of ouabain and was substantially inhibited by oligomycin. The corresponding component of pNPPase activity was partially inhibited by ouabain or by removal of most of the K, but was little affected by oligomycin. The phosphatidylserine-dependent enzyme(s) therefore exhibited properties characteristic of the ATPase of the Na pump.4. Phosphatidylserine dispersions similarly activated both the ATPase and the pNPPase of the particulate enzyme preparations, untreated with deoxycholate.5. The results suggest that the system for active transport of Na and K involves a complex unit of phosphatidylserine and the protein of the ATPase.

Adenosine Triphosphatases↗
PubMed1969

Ion movements in human red cells independent of the sodium pump.

1. A study was made of the dependence on external Na of the movements of Na and K in human red cells. Special attention was given to ouabain-insensitive movements. The effect of internal Na on Na influx, and the influence of some sulphydryl inhibitors on ion movements and metabolism was also investigated.2. External Na stimulated ouabain-insensitive Na efflux and K influx. There was also a ouabain-insensitive component of Na influx that was raised on increasing the internal Na concentration. Exchange diffusion of Na appears to occur in the presence of ouabain and external K.3. Net transport of Na and K in the presence of ouabain was independent of external Na, as was also lactate production.4. Ethacrynic acid partially inhibited the Na pump; the Na-dependent components of Na efflux and K influx in the presence of ouabain were completely inhibited by ethacrynic acid. Both ouabain-sensitive and ouabain-insensitive adenosinetriphosphatase activities were inhibited by ethacrynic acid indicating a non-specific effect of this compound. Iodoacetamide decreased only the ouabain-insensitive ATPase activity.5. The results suggest that when the Na pump is blocked by ouabain, part of the residual ion movements can be attributed to exchange diffusion.

Adenosine Triphosphatases↗
PubMed1968

The influence of external sodium ions on the sodium pump in erythrocytes.

1. A study has been made of the interaction between Na(+) and K(+) on the adenosine triphosphatase activity of erythrocyte ;ghosts', and on the K(+) influx and Na(+) efflux of intact erythrocytes. The adenosine triphosphatase activity and the ion movements were greater at a low external K(+) concentration in the absence of Na(+) than they were in the presence of 150mm-Na(+). The inhibition by external Na(+) of K(+) influx had an inhibitory constant of 5-10mm. 2. Activation by K(+) of kidney microsomal adenosine triphosphatase was retarded by Na(+), and activation by Na(+) was retarded by K(+). Fragmented erythrocyte membranes behaved similarly. 3. These observations suggest that there is competition between Na(+) and K(+) at the K(+)-sensitive site of the membrane.

Adenosine Triphosphatases↗
PubMed1968

The influence of ions on the labelling of adenosine triphosphate in red cell ghosts.

1. The ionic composition of human red cell ghosts and suspending Ringer solutions have been varied independently. Measurements were made of the incorporation of [(32)P]o-phosphate ((32)P(i)) into ATP associated with different concentration gradients of Na and K across the membrane.2. Some incorporation of (32)P(i) was always found irrespective of the ionic composition of ghosts or media. However, additional labelling of energy-rich phosphate occurred when low Na, high K ghosts were incubated in a high Na, K-free medium. This did not occur when there was only a gradient of either Na or K. Downhill movements of both Na into and K out of the ghosts were needed for the extra labelling.3. Even in the presence of suitable ionic gradients, the extra incorporation was prevented by ouabain or by adding a small amount of external K sufficient to facilitate normal operation of the Na pump.4. Increase in internal P(i) stimulated the incorporation.5. The results show that the conditions for forward and backward running of the ATPase system associated with the Na pump are such that both reactions cannot proceed optimally at the same time.

Adenosine Triphosphatases↗
PubMed1968

Some aspects of adenosine triphosphate synthesis from adenine and adenosine in human red blood cells.

1. The synthesis of ATP has been studied in human erythrocytes. Fresh cells showed no net synthesis of ATP when incubated with adenine or adenosine, although labelled adenine was incorporated into ATP in small amounts.2. Cold-stored cells (3-6 weeks old) became progressively depleted of adenine nucleotides but incubation with adenosine or adenine plus inosine restored the ATP concentration to normal within 4 hr. Incorporation of labelled adenine or adenosine into the ATP of incubated stored cells corresponded to net ATP synthesis by these cells.3. Synthesis of ATP from adenosine plus adenine together was 75% derived from adenine and only 25% from adenosine, indicating that nucleotide synthesis from adenine inhibits the simultaneous synthesis of nucleotide from adenosine.

Adenine↗
PubMed1967

The metabolic response of brain slices to agents affecting the sodium pump.

1. Slices of brain cortex from rabbits were incubated in Ringer solution and in Ringer modified by the removal of calcium and sodium, and the addition of ouabain, oligomycin or extra potassium. The potassium content of the tissue, the oxygen consumption and the lactate production from glucose were measured and found to be interrelated.2. Incubation in high-K Ringer caused an increase in oxygen consumption that was prevented by ouabain, oligomycin and deprivation of sodium. Lactate production was also raised, but this increase was unaffected by ouabain and raised further by oligomycin.3. Calcium omission raised metabolism; the tissue K content was unaffected. Oligomycin always decreased oxygen consumption and raised lactate production further. The metabolic responses to calcium, potassium, ouabain and oligomycin depended on sodium.4. After anaerobic incubation, the tissue potassium concentration was still 5 times higher than that in Ringer. It was unaffected by oligomycin but lowered markedly by ouabain.5. The synergistic effects of sodium with potassium, oligomycin, calcium, and calcium plus ouabain suggest that the metabolic responses of brain cortex slices to a high-K Ringer depend on the operation of the sodium pump.

Animals↗
PubMed1967

Potassium transport and nucleoside metabolism in human red cells.

1. A study has been made of active cation transport in relation to the metabolism of nucleosides and deoxynucleosides in human red blood cells.2. Lactate production from inosine depended on the cellular inorganic phosphate available for phosphorolysis and was raised to some 4 times the normal rate from glucose. Inosine inhibited glucose metabolism according to the amount of glucose-6-phosphate produced. Guanosine behaved similarly, but glucose-6-phosphate was not formed from adenosine, deoxyinosine and deoxyguanosine.3. Glucose metabolism was related to the ATP content of the cells, which was raised by incubation with adenosine, or with inosine plus adenine.4. Adenosine and deoxyadenosine raised the potassium influx above the values found with inosine and deoxyinosine under conditions when the lactate production was constant. Active potassium influx was correlated with the ATP concentration in the cells, but independent of the lactate production when the latter was raised above normal.

Adenosine Triphosphate↗