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383 SIRT5-catalyzed demalonylation and inactivation of SDHA block the TCA cycle and induce succinate accumulation, promoting tumorigenesis and drug resistance

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8, October 2000:1157-1161

if a duct is blocked (by a gallstone, scar-like narrowing/stricture, or a tumor), the drug cant reach its target and adding more bile acids can worsen the backup (jaundice, itching, rising bilirubin/ALP)