Dichloroacetate inhibits glutamine oxidation by decreasing pyruvate availability for transamination.
We have shown that dichloroacetate (DCA) inhibits growth, glutamine oxidation, and pyruvate and alanine production in a concentration-dependent manner in PQXB 1/2 hybridoma cells. The use of inhibitors indicates that glutamine oxidation proceeds by an aminooxyacetate-sensitive transamination reaction in this cell line. Addition of pyruvate to DCA-treated cells restored glutamine oxidation to control values. Our data suggest that DCA inhibits glutamine oxidation by decreasing the availability of pyruvate for transamination, which in turn results in glutamate accumulation and a consequent inhibition of glutaminase activity. Impaired glutamine catabolism in the presence of DCA has subsequent effects on overall metabolic balance and cell maintenance and growth.
Murray
K
K
School of Biological Sciences, University of Manchester, UK.
Dickson
A J
AJ
D000409:Alanine / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005973:Glutamine / Q000187:drug effects / Q000378:metabolism*; D006825:Hybridomas / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D019289:Pyruvic Acid / Q000378:metabolism*; D013997:Time Factors
D005973:Glutamine; D019289:Pyruvic Acid; D003999:Dichloroacetic Acid; D000409:Alanine