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Property "Has-20abstract" (as page type) with input value "Sirtuins-20are-20NAD-3Csup-3E+-3C-2Fsup-3E-2Ddependent-20protein-20deacylases-20that-20regulate-20several-20aspects-20of-20metabolism-20and-20aging.-20In-20contrast-20to-20the-20other-20mammalian-20sirtuins,-20the-20primary-20enzymatic-20activity-20of-20mitochondrial-20sirtuin-204-20(SIRT4)-20and-20its-20overall-20role-20in-20metabolic-20control-20have-20remained-20enigmatic.-20Using-20a-20combination-20of-20phylogenetics,-20structural-20biology,-20and-20enzymology,-20we-20show-20that-20SIRT4-20removes-20three-20acyl-20moieties-20from-20lysine-20residues:-20methylglutaryl-20(MG)-2D,-20hydroxymethylglutaryl-20(HMG)-2D,-20and-203-2Dmethylglutaconyl-20(MGc)-2Dlysine.-20The-20metabolites-20leading-20to-20these-20post-2Dtranslational-20modifications-20are-20intermediates-20in-20leucine-20oxidation,-20and-20we-20show-20a-20primary-20role-20for-20SIRT4-20in-20controlling-20this-20pathway-20in-20mice.-20Furthermore,-20we-20find-20that-20dysregulated-20leucine-20metabolism-20in-20SIRT4KO-20mice-20leads-20to-20elevated-20basal-20and-20stimulated-20insulin-20secretion,-20which-20progressively-20develops-20into-20glucose-20intolerance-20and-20insulin-20resistance.-20These-20findings-20identify-20a-20robust-20enzymatic-20activity-20for-20SIRT4,-20uncover-20a-20mechanism-20controlling-20branched-2Dchain-20amino-20acid-20flux,-20and-20position-20SIRT4-20as-20a-20crucial-20player-20maintaining-20insulin-20secretion-20and-20glucose-20homeostasis-20during-20aging.-0A-0ACopyright-20©-202017-20Elsevier-20Inc.-20All-20rights-20reserved." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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