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Savishinsky 1974

10.1152/ajprenal.00511.2006 34 GuazziM.BrennerD

Typically, citrate is either retained and oxidized in the mitochondria to generate energy as an essential intermediate in the citric acid cycle, or is exported into the cytoplasm where it is cleaved by ATP citrate lyase (ACLY) to generate acetyl-CoA, which is used for fatty acid (FA) synthesis ( The normal human prostate retains the capability of accumulating the highest levels of zinc in any soft tissue of the human body through expression of specific zinc transporters (ZIP14 for uptake and ZnT110 for release) ( Marked decrease in zinc levels due to depletion of ZIP1 represents an essential early event in the development of PCa malignancy ( 18 F-FDG in primary PCa ( AR Drives PCa by Regulating Central Metabolism Multi-omics studies (transcriptome, proteomics, cistrome, and metabolome) define the AR as a master regulator that orchestrates cellular metabolism to fuel proliferation and growth of PCa cells ( Glucose Metabolism AR determines bioenergetic traits through regulation of components in glycolytic pathway (GLUT1, HK1, HK2, and PFK2/PFKFB) and pyruvate flux into mitochondria (PDH, MPC2) ( 13 C magnetic resonance spectroscopic imaging (MRSI) demonstrates that in vivo conversion [1- 13 C] lactate into [1- 13 C] pyruvate occurred more efficiently in PDX models of AR-driven CRPC than those of AR-negative PCa ( FA Metabolism AR regulates FA metabolism by controlling expression of more than 20 enzymes involved in many aspects of lipid metabolism, including uptake, trafficking, synthesis, and degradation ( AR and the master regulator of lipid homeostasis sterol regulatory-element binding protein (SREBP) regulate each other in a positive feedback system (56, 57)