Erythrocyte Metabolism. The Metabolic Behavior of the Cholesterol of Human Erythrocytes 1

Abstract

In the course of studies on the ageing process in the human erythrocyte, we have investigated the metabolic behavior of the cholesterol of the erythrocyte. This study was designed to determine whether the cholesterol of the human erythrocyte is in the dynamic state (2), or whether the cholesterol is incorporated into the newly formed erythrocyte and remains with the cell throughout the cell's life span, as does hemoglobin (3-6).A previous study (7) has shown that the cholesterol of the plasma is in the dynamic state. The rate of entry of cholesterol into the plasma of the circulating blood was measured by determining the rate at which deuterium is incorporated into the cholesterol of the plasma when an elevated concentration of deuterium in the body water is maintained at a steady level by repeated administration of deuterium oxide. In the studies described in this report, the same technique has been employed and the concentrations of deuterium in the cholesterol of the erythrocytes and of the plasma have been compared. Since the cholesterol of the plasma is in the dynamic state, the finding of a similar rate of turnover and a similar pattern of concentrations of deuterium in the cholesterol of the erythrocytes would favor the conclusion that the cholesterol of the erythrocytes is also in the dynamic state.The subjects of this study were a patient with the nephrotic syndrome and a patient with xanthomatosis tuberosum multiplex. A discussion of the mechanisms involved in the maintenance of hypercholesterolemia in these conditions is beyond the scope of this paper and will not be presented here. MATERIAL AND METHODSSubjects: 1) F. G., a 36 year old Negro woman, was studied during the nephrotic phase of chronic glomerulonephritis. Pertinent laboratory data included a red blood cell count of 3.5 million per cubic millimeter, hemoglobin of 10.0 Gm. per 100 ml. of blood, and venous hematocrit of 33 per cent; plasma total cholesterol 836 mg. per cent with 70 per cent of the total cholesterol esterified; erythrocyte total cholesterol 146 mg. per cent with 11 per cent of the total in the ester form and 89 per cent in the form of free cholesterol.2) M. T., a 21 year old white woman with xanthoma tuberosum multiplex, was essentially asymptomatic. Hematologic data included a red blood cell count of 4.2 million per cubic millimeter and a hemoglobin value of 13.0 Gm. per 100 ml. of blood. Plasma total cholesterol was found to range between 500 mg. per cent and 660 mg. per cent with 71 to 75 per cent of the total esterified. Erythrocyte total cholesterol was 132 mg. per cent with 95 per cent of the total in the form of free cholesterol and 5 per cent in ester form.Administration of deuterium oxide: 1) Subject F. G. drank 1000 ml. of 50 per cent D2O in four divided doses on the first day of the experiment and then received 60 to 65 ml. per day of approximately 30 per cent D20 for the next 112 days. On 11 occasions the daily dose was doubled in order to maintain the body water concentration of deuterium at a steady level. The co...

Human cholesterol synthesis measurement using deuterated water. Theoretical and procedural considerations.

“…Later, in humans, London and Schwartz 12 showed a parallel rise in plasma and erythrocyte cholesterol deuterium enrichment over several weeks in two subjects given regular doses of D 2 O. This study was the first reported use of a stable-isotope tracer in the study of human lipid metabolism; at that time, radiolabeled nuclides were tracers of choice in studying cholesterogenesis.…”

“…In each case the asymptote to the plateau value was well below that predicted by the simple model. Long-term enrichment data in humans from London and Schwarz 12 have also shown a tendency toward a plateau below the theoretical prediction when modeled with a monoexponential fit.…”

“…Indeed, in a single subject given continual deuterium doses, plasma total cholesterol deuterium enrichment continued to increase after 100 days. 12 The initial 1-2-day period after deuterium dosing is considered to yield the most interpretable synthesis data for several reasons. First, during the immediate postdose interval, movement of labeled cholesterol out of the rapid-turnover compartment is small; thus, uptake rates are relatively linear.…”

“…12 In pigs, exponential inflection in deuterium enrichment in erythrocyte cholesterol is detectable at 48 hours and pronounced at 96 hours. 29 In groups of pigs fed both cholesterol-free and 0.5% cholesterol-containing diets, monoexponential fits using the corrected water-enrichment level as the predicted plateau resulted in poor curve fits for deuterium enrichment.…”

The exchange of 131I-labelled lipid and 131I-labelled protein between red cells and serum

“…The exchange of lipids between blood cells and plasan has been suggested previously. Zilversmit, Entenman, Fishler & Chaikoff (1943), Muir, Perrone & PopjAk (1951) and London & Schwarz (1953) have stated that there is a free exchange of cholesterol between red cells and plasma. Goodman (1958) has shown that there is a rapid exchange of unesterified fatty acids between blood cells and plasma.…”