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Metabolism of ketone bodies, oleate and glucose in lymphocytes of the rat.

ABSTRACT: Isolated incubated lymphocytes utilized acetoacetate, 3-hydroxybutyrate or oleate at about 0.5 mumol/min per g dry wt. These rates were not markedly affected by concanavalin A or by starvation of the donor animal. When ketone bodies replaced glucose in the culture medium, they could not support lymphocyte proliferation when cells were cultured for 48 h. Addition of oleate (0.5 mM) to isolated lymphocytes increased the rate of O2 consumption markedly, suggesting that it could contribute about 30% to O2 consumption. The rate of oleate uptake and the stimulated rate of O2 consumption were maximal at 0.5 M-oleate; this is in contrast with the effect in some other tissues, in which the rate of fatty acid oxidation is linear with concentration up to about 2 mM. Since the normal plasma concentration of fatty acid in the fed state is about 0.5 mM, this suggests that lymphocytes can utilize fatty acids at a maximal rate in the fed state. Ketone bodies or oleate decreased the rate of glucose utilization by incubated lymphocytes; ketone bodies decreased the rate of pyruvate oxidation and increased the intracellular concentration of hexose monophosphate and citrate, suggesting that 6-phosphofructokinase is inhibited by citrate, and hexokinase by glucose 6-phosphate. These effects may be important not so much in conserving glucose in the whole animal but in maintaining the concentrations of glycolytic intermediates necessary for biosynthetic processes during proliferation.

SUBMITTER: Ardawi MS

PROVIDER: S-EPMC1144027 | biostudies-other | 1984 Jul

REPOSITORIES: biostudies-other

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Project description:Maximum activities of some key enzymes of metabolism were studied in elicited (inflammatory) macrophages of the mouse and lymph-node lymphocytes of the rat. The activity of hexokinase in the macrophage is very high, as high as that in any other major tissue of the body, and higher than that of phosphorylase or 6-phosphofructokinase, suggesting that glucose is a more important fuel than glycogen and that the pentose phosphate pathway is also important in these cells. The latter suggestion is supported by the high activities of both glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. However, the rate of glucose utilization by 'resting' macrophages incubated in vitro is less than the 10% of the activity of 6-phosphofructokinase: this suggests that the rate of glycolysis is increased dramatically during phagocytosis or increased secretory activity. The macrophages possess higher activities of citrate synthase and oxoglutarate dehydrogenase than do lymphocytes, suggesting that the tricarboxylic acid cycle may be important in energy generation in these cells. The activity of 3-oxoacid CoA-transferase is higher in the macrophage, but that of 3-hydroxybutyrate dehydrogenase is very much lower than those in the lymphocytes. The activity of carnitine palmitoyltransferase is higher in macrophages, suggesting that fatty acids as well as acetoacetate could provide acetyl-CoA as substrate for the tricarboxylic acid cycle. No detectable rate of acetoacetate or 3-hydroxybutyrate utilization was observed during incubation of resting macrophages, but that of oleate was 1.0 nmol/h per mg of protein or about 2.2% of the activity of palmitoyltransferase. The activity of glutaminase is about 4-fold higher in macrophages than in lymphocytes, which suggests that the rate of glutamine utilization could be very high. The rate of utilization of glutamine by resting incubated macrophages was similar to that reported for rat lymphocytes, but was considerably lower than the activity of glutaminase.

Project description:1. Diaphragms from 48h-starved rats were incubated in Krebs-Ringer bicarbonate medium at 37degreesC for 30min and then transferred into new medium and incubated for 1, 2 and 3 h. 2. The amount of free amino acids found at the end of each time of incubation was larger than the amount at the beginning of incubation, indicating that in this system proteolysis is prevailing. 3. The diaphragms was releasing mainly alanine and glutamine into the incubation medium. 4. Within the periods of incubation the release and metabolism of free amino acids was proceeding at a constant rate. 5. Addition of sodium DL-3-hydroxybutyrate decreased the tissue content of several amino acids, among which were tyrosine and phenylalanine, suggesting that proteolysis was decreased by ketone bodies. 6. In the presence of glucose (10mM) and branched-chain amino acids (0.5mM), sodium DL-3-hydroxybutyrate at concentrations of 4 or 6 mM resulted in 30% decrease in tissue alanine content and a 20% decline in alanine release. Release of taurine and glutamine was decreased by 19 and 16% respectively with 6 mM-sodium DL-3-hydroxybutyrate. Addition of sodium acetoacetate (1-3mM) also resulted in a 20-35% decrease in tissue content of alanine, glutamine and taurine and in a 15-24% decrease of alanine and glutamine release. Smaller decreases (less than 15%) in the release of glycine, threonine, proline, serine and aspartate were also observed in the presence of sodium DL-3-hydroxybutyrate or sodium acetoacetate. 7. Substitution of pyruvate (1.0mM) for glucose in the presence of acetoacetate restored alanine and glutamine production to control values. In the presence of acetoacetate, pyruvate also increased the tissue content of aspartate by 77% and decreased the tissue content of glutamate by 30%. 8. It is suggested that in diaphragms from starved rats, ketone bodies (a) in the absence of other substrates inhibit protein catabolism and (b) in the presence of glucose and branched-chain amino acids decrease alanine and glutamine production, by inhibiting glycolysis.

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Metabolism of ketone bodies, oleate and glucose in lymphocytes of the rat.

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