Distribution of phosphorylated metabolites and magnesium in the red cells
of a patient with hyperactive pyruvate kinase
R Ouwerkerk, CJ van Echteld, GE Staal and G Rijksen
Department of Haematology, University Hospital, Utrecht, The Netherlands.
The intracellular distribution of adenosine 5'-triphosphate (ATP) and
2,3-diphosphoglycerate (2,3-DPG) was studied in the red cells of a patient
with a "high-ATP syndrome" by using 31P nuclear magnetic resonance. In this
patient, red cell ATP was increased 2.5-fold, whereas 2,3-DPG was decreased
fourfold due to the presence of a hyperactive pyruvate kinase. In
oxygenated red cells, these abnormal concentrations were reflected to the
same extent in all complexes in which ATP and 2,3-DPG take part. The
diminished amount of 2,3-DPG bound to hemoglobin was almost completely
replaced by ATP-hemoglobin complexes. Therefore, free hemoglobin was only
slightly increased. In deoxygenated cells, the relative distribution of ATP
and 2,3-DPG complexes was significantly disturbed. The main difference was
a shift in the ratio of magnesium ATP (MgATP) over the ATP-hemoglobin
complex; 74% of total ATP was complexed to hemoglobin (45% in normal
cells), whereas the concentration of MgATP was only slightly increased with
respect to normal. The shortage in 2,3-DPG bound to hemoglobin could
partially be replenished by an increase in hemoglobin (Mg) ATP complexes.
Therefore, the amount of uncomplexed hemoglobin raised from 15% in normal
cells to 38% in the patient's cells. As a result, the oxygen-dissociation
curve was only moderately shifted to the left. It is concluded that the
regulatory role of 2,3-DPG in oxygen transport is taken over in part by
(Mg) ATP in this patient. In both aerobic and anaerobic cells, the increase
in magnesium bound to ATP, either free or bound to hemoglobin, exceeds the
decrease in 2,3-DPG Mg complex. In spite of this, the amount of
intracellular free Mg++ was normal or slightly lowered. This suggests the
presence of a compensatory mechanism by which the amount of total cellular
magnesium could be increased.
Volume 72,
Issue 4,
pp. 1224-1229,
10/01/1988
Copyright © 1988 by The American Society of Hematology
