Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.3.3.1 (
citrate synthase
)
4,488
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Indole-3-acetic acid
(
IAA
) is toxic for human tumor cells and in association with horseradish peroxidase (HRP) can be used as a new prodrug/enzyme combination for targeted cancer therapy. The toxic effect of
IAA
on neutrophils, macrophages and lymphocytes is associated with cell peroxidase activity, which is high in neutrophils and low in lymphocytes. The effect of
IAA
on glucose and glutamine metabolism in leukocytes presenting different peroxidase activities: neutrophils, thioglycollate-elicited macrophages and lymphocytes was investigated. A time-course effect (from 6 to 48 h in culture) of
IAA
on glucose and glutamine metabolism of neutrophils, thioglycollate-elicited macrophages, and lymphocytes was then carried out. Addition of
IAA
(0.25 mM) did not have a marked effect on glucose utilization and lactate formation by the three cell types but it raised glutamine consumption and glutamate production by neutrophils and macrophages.
IAA
had no effect on glutamine consumption and glutamate production by lymphocytes. A strong relationship was found between glutamine utilization (0.999) and glutamate production (0.999) and peroxidase activity.
IAA
did not change the activities of hexokinase, glucose-6-phosphate dehydrogenase,
citrate synthase
, lactate dehydrogenase, and phosphate-dependent glutaminase of 24 h cultured neutrophils and lymphocytes. The effect of
IAA
(1 mM) on glucose and glutamine metabolism was also investigated by 1 h incubated leukocytes in PBS.
IAA
did not affect glucose and glutamine metabolism of lymphocytes but enhanced glucose and glutamine metabolism by 1 h incubated neutrophils and thioglycollate-elicited macrophages.
IAA
caused a marked increase on oxygen consumption by neutrophils, which was more pronounced in the presence of the glutamine as compared to glucose. The stimulation of oxygen consumption leads to a reduction in NADH/NAD+ ratio that activates the flux of substrates through the Krebs cycle. Since glutamine is mainly metabolized through the left hand side of the Krebs cycle, a reduction in the redox state of the cells may accelerate the flux of substrates through glutaminolysis. The toxic results presented here show that the affect of
IAA
in association with peroxidase involves activation of glutamine metabolism.
...
PMID:Indole-3-acetic acid increases glutamine utilization by high peroxidase activity-presenting leukocytes. 1526 71
