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Abstract
The red cell adenosine triphosphate (ATP) of uremic subjects was 70 per cent higher
than that of healthy subjects. The elevated ATP in uremic red cells was not explained
by the effect of anemia or increased reticulocytes on the concentration of red cell
organic phosphate compounds; rather, red cell ATP concentration was highly correlated
with serum phosphorus. The rate of red cell glucose utilization and lactate production
was also greater in uremic hyperphosphatemic subjects than in healthy subjects. Plasma
from uremic hyperphosphatemic subjects increased the ATP concentration, glucose utilization,
and lactate production of normal red cells, whereas normophosphatemic normal plasma
lowered the ATP concentration, glucose utilization, and lactate production of red
cells from uremic subjects. Addition of phosphate to normal blood in concentrations
similar to those seen in uremia increased the red cell ATP concentration, glucose
utilization, and lactate production to rates seen in red cells of uremic subjects.
Total red cell membrane adenosine triphosphatase (ATPase) was not significantly different
in normal and uremic subjects. The rate of ATP hydrolysis in red cells suspended in
autologous plasma containing 2.5 × 10−2M sodium fluoride was similar in uremic and healthy subjects. Red cell 2,3-diphosphoglycerate
(2,3-DPG) was elevated in uremic subjects, was correlated with plasma phosphate, and
could be increased to concentrations seen in uremic red cells by adding phosphate
to normal blood or by placing normal red cells in uremic hyperphosphatemic plasma.
Anemic subjects had higher red cell 2,3-DPG and lower ATP concentrations than anemic
uremic subjects, although the total of these glycolytic intermediates was similar
in amount in the two groups. Red cell 2,3-DPG in anemia due to decreased red cell
production is associated with the severity of anemia in the absence of hyperphosphatemia
(uremia). In uremic subjects, hyperphosphatemia is an additional determinant in the
elevated glycolytic rate, ATP, and 2,3-DPG concentration. The additional contribution
of hyperphosphatemia may explain in, part the preferential increase in ATP in uremic
anemic as compared to nonuremic subjects with reticulopenic anemias.
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References
- The kidney and erythropoiesis.Amer. J. Med. 1968; 44: 725
- Inhibition of protein synthesis by N-methyl-2-pyridone-5-formamidoacetic acid and other compounds isolated from uremic patients.Yale J. Biol. Med. 1965; 38: 273
- Erythropoiesis in patients with renal failure undergoing chronic dialysis.New Eng. J. Med. 1967; 276: 653
- Microangiopathic haemolytic anaemia: The possible role of vascular lesions in pathogenesis.Brit. J. Haemat. 1962; 8: 358
- Evidence that guanidines and some related compounds cause haemolysis in chronic uremia.Clin. Sci. 1968; 34: 141
- Adenosine triphosphate and shape of erythrocytes.J. Biochem. (Tokyo). 1961; 49: 487
- A direct relationship of adenosine triphosphate level and in vivo viability of erythrocytes.Nature. 1902; 194: 877
- Lowered glucose utilization, phosphate uptake, and reduced glutathione content of erythrocytes following bilateral nephrectomy.J. Lab. Clin. Med. 1958; 51: 49
- Study of the effect of uremic metabolites on erythrocyte glycolysis.Metabolism. 1964; 13: 629
- Effect of dialysis and purine ribosides upon the anemia of uremia.J. Clin. Invest. 1957; 36: 923
- The ADP and ATP levels and the phosphorylating activity of erythrocytes in patients with uremia associated with chronic renal failure.Tohoku J. Exp. Med. 1964; 84: 105
- Erythrocyte production and metabolism in anephric and uremic men.Ann. N. Y. Acad. Sci. 1968; 149: 539
- Organic phosphate compounds of erythrocytes from individuals with uremia.J. Lab. Clin. Med. 1964; 64: 675
- An ion transport defect in erythrocytes from uremic patients.Trans. Ass. Amer. Physicians. 1964; 77: 169
- Ionic effects on firefly bioluminescence assay of red blood cell ATP.Anal. Biochem. 1966; 17: 268
- Is hemoglobin an essential structural component of human erythrocyte membranes?.J. Clin. Invest. 1963; 42: 581
- The photometric microdetermination of blood glucose with glucose oxidase.J. Lab. Clin. Med. 1958; 51: 448
- Determination of 1-lactate.in: Bergmeyer H.U. Methods of enzymatic analysis. Academic Press, Inc, New York1963: 123
- Adenosine-5-triphosphate determination with phosphoglycerate kinase.in: Bergmeyer H.U. Methods of enzymatic analysis. Academic Press, Inc, New York1963: 539
- Kinetik des 2,3-diphosphoglyceratumsatzes in menschlichen erythrocyten.Biochem. Z. 1965; 341: 387
- d-2,3-diphosphoglycerate.in: Bergemeyer H.U. Methods of enzymatic analysis. Academic Press, Inc, New York1963: 238
- The role of erythrocyte intermediates in “Programing” for oxygen release in normal human and in hypoxic diseases.J. Clin. Invest. 1969; 48: 11a
- Metabolic dependence of red cell deformability.J. Clin. Invest. 1969; 48: 795
- Studies on the preservation of human blood. II. The relationship of erythrocyte adenosine triphosphate levels and other in vitro measures to red cell storageability.J. Lab. Clin. Med. 1967; 69: 968
- Inhibition of lactic dehydrogenase by ultra-filtrate of uremic blood.Metabolism. 1963; 12: 1051
- Über die aktivierung der glykolyse in menschlichen erythrocyten durchanorganisches phosphat.in: Habil. Schrift, München. 1963
- Role of inorganic phosphate in stimulating glucose utilization of human red blood cells.Biochem. Biophys. Res. Comm. 1964; 15: 33
- Inorganic phosphate and enhanced glucose degradation by intact erythrocytes.J. Biol. Chem. 1965; 240: 2806
- Control of glycolysis in human red blood cells.J. Biol. Chem. 1966; 241: 4848
- Erythrocyte adenosine triphosphate depletion during hypophosphatemia in a uremic subject.New Eng. J. Med. 1969; 280: 240
- Beobachtungen bei der phosphat-aktivierung der erythrocyten-glykolyse.in: Metabolism and membrane permeability of erythrocytes and thrombocytes. 1st Inter. Symp. Vienna. June 17 to 20, 1968: 19
- Intracellular organic phosphates as regulators of oxygen release by haemoglobin.Nature. 1969; 221: 618
- Improved oxygen release: adaptation of mature red cells to hypoxia.J. Clin. Invest. 1968; 47: 1851
- Red-cell phosphate and hemoglobin oxygen affinity in uremia.New Eng. J. Med. 1969; 281: 966
Lichtman, M. A., Miller, D. R., and Cohen, J.: Reduced red cell glycolysis, 2,3-diphosphoglycerate and adenosine triphosphate and increased hemoglobin-oxygen affinity during severe hypophosphatemia induced by hyperalimentation. Unpublished observations.
Lichtman, M. A.: Divalent cation content of erythrocyte membranes. In preparation.
- Erythrocyte metabolism and function: Hexokinase inhibition by 2,3-diphosphoglycerate and interaction with ATP and Mg2+.Biochem. Biophys. Acta. 1969; 192: 157
- On a regulatory system of the adenine level in the plasma connected with red cell maturation and its effect on the adenine nucleotides of the circulating erythrocyte.Blood. 1969; 33: 617
Article info
Publication history
Accepted:
May 25,
1970
Received:
October 8,
1969
With the technical assistance of VAUDEEN ABEL, ELIZABETH KEARNEY and CLARA LOCKWOODFootnotes
☆These studies were supported by United States Public Health Service Grants HE-06241-07 and AM-13947-01, a United States Public Health Service General Research Support Grant, research grants from the Monroe County Cancer and Leukemia Society, the Nutrition Foundation, Inc., and by the United States Atomic Energy Commission at the University of Rochester Atomic Energy Project and has been assigned publication No. UR-49-1257.
☆☆Presented in part at the meeting of the Association of American Physicians, Atlantic City, N. J., May 6, 1969.
Identification
Copyright
© 1970 Published by Elsevier Inc.
