Stimulatory effect of fatty acid treatment on glucose utilization in human erythrocytes.
We previously reported that treatment of human erythrocytes with bee venom phospholipase A2 increased the rate of lactate production from glucose. This increase was suggested to be mediated through liberation of free fatty acids from membrane phospholipids. So, in the present study we examined the mechanism of stimulation of glycolysis by fatty acids. Treatment of intact erythrocytes with most of the 15 fatty acids tested resulted in stimulation of lactate production from glucose. Among the fatty acids tested, myristoleic acid showed the highest stimulatory activity. The ratio of moles of lactate produced to those of glucose utilized was about 1.9 in both myristoleic acid-treated and untreated cells. Treatment of erythrocytes with myristoleic acid did not affect the amount of 2,3-bisphosphoglycerate. Lactate production from D-glyceraldehyde, which is thought to be phosphorylated to D-glyceraldehyde 3-phosphate and then metabolized in the glycolytic pathway, was not at all affected by treatment of cells with myristoleic acid. The cross-over plot of glycolytic intermediates suggested that the enhancement of glycolysis was induced by activation of the 6-phosphofructokinase (PFK) step. Fatty acids incorporated into erythrocytes were found to be present predominantly in the cytoplasm rather than in the plasma membrane. The PFK activity, but not the hexokinase activity, in hemolysates was clearly increased by a set of fatty acids, and myristoleic acid was again the most potent. However, partially purified human erythrocyte PFK was not activated by the acid. We conclude that fatty acids stimulate glycolysis through activation of PFK in cooperation with some other component(s) in erythrocytes.
Duan
Y J
YJ
Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Murase
S
S
Okuda
J
J
Tamura
A
A
Miwa
I
I
D004789:Enzyme Activation; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D005227:Fatty Acids / Q000494:pharmacology*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000032:analysis; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D006593:Hexokinase / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D010732:Phosphofructokinase-1 / Q000378:metabolism
D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D005230:Fatty Acids, Nonesterified; D019344:Lactic Acid; D006593:Hexokinase; D010732:Phosphofructokinase-1; D005947:Glucose; C054211:9-tetradecenoic acid