Index A Aerobic metabolism , 194 Acetylated , 127 Age-associated cardiac hypertrophy , 160 Acetylated histones , 140 Age-associated chronic infl ammatory Acetylation , 41 , 42 , 47–59 , 108 , 118 diseases , 157 abrogates lysine charge , 107–109 Age-related diseases , 171 lysine , 42 , 47 , 49 , 59 Aging , 149 , 213 regulation , 53 , 54 increased infl ammation , 156 mimetics , 110 molecular mechanisms of , 149 of PGC-1α , 153 Agouti-related protein (AgRP) , 94 , 95 Acetyl-CoA carboxylase (ACC) , 195 Akt-mediated phosphorylation , 73 Acetyl CoA synthase 2 (ACS2) , 244 Aldehyde dehydrogenase 2 (Aldh2) , 47 Acetyltransferases , 50 Allosteric regulation, GDH , 126–128 acH3K56 deacetylation by SIRT6 , 158 Alpha-peptidyl-imidate , 4 Acipimox , 36 Alternative end-joining (A-EJ) , 158 Activator protein 1 (AP-1) transcription Alzheimer’s disease , 253 factor , 153 a-melanocyte-stimulating hormone (α-MSH) , Active regulator of SIRT1 (AROS) , 12 , 79 94 Acyl-CoA dehydrogenase (ACAD) , 121 Amino acids , 85 Acyl-CoA levels , 55 catabolism , 244 Adaptive vascular remodeling , 200–202 nonessential , 175 Adenine nucleotide transporter (ANT) , 48 peptide , 19 Adenoma-prone SIRT6-defi cient mice with tryptophan , 30 DCA , 162 α-amino-β-carboxymuconate-ε-semialdehyde Adenosine-5’-triphosphate , 172 (ACMS) , 30 Adenosine triphosphate (ATP) , 128 AMP-activated protein kinase (AMPK) , 14 , Adenoviral shRNA delivery , 86 79 , 193 , 195 , 200 , 235 , 249 , 256 Adenylyltransferase activity , 31 Anaphase-promoting complex/cyclosome Adipocyte fatty acid binding protein (APC/C) , 185 (A-FABP) , 154 Angiogenic factors , 200 Adipocytes , 14 , 91 Angiopoietin-like protein 4 (ANGPTL4) , 153 Adipose tissue infl ammation , 91 Angiotensin II (Ang II) treatment , 161 ADP-ribosylation , 2 , 140 Anoikis , 176 ADP-ribosyltransfer , 2 , 6 , 140 Anti-aging effects of caloric restriction , 218 ADPR-thioimidates , 6 Antisense oligonucleotides , 85 Aerobic exercise , 201 Apoptosis , 8 , 13 Aerobic glycolysis , 173 Archaea , 1 © Springer Science+Business Media Dordrecht 2016 275 R.H. Houtkooper (ed.), Sirtuins, Proteins and Cell Regulation 10, DOI 10.1007/978-94-024-0962-8 276 Index Arcuate nucleus (ARC) , 94 Brain, SIRT6 defi ciency in , 154 Arginine , 42 Brain-specifi c Sirt1 −/− (BSKO) , 231 Aryl hydrocarbon receptor nuclear Brain-specifi c Sirt6 KO mice , 154 translocator-like (ARNTL) BRASTO mice , 94 protein , 154 Breast cancer cell lines, SIRT6 , 163 ASCT2 ( SLC1A5 ), glutamine transporters , 175 Brown adipose tissue (BAT) , 15 , 91 , 92 Aspartate aminotransferase (AST) , 51 , 143 Budding yeast protein , 149 Assisted allosteric activation (AAA), proposed Budding yeast, Sir2 overexpression in , 159 mechanism of , 247 Ataxia telangiectasia and Rad3-related (ATR) kinases , 79 C Atherogenesis , 257 cADP-ribose synthase , 34 , 75 ATP-dependent chromatin remodeling , 236 Caenorhabditis elegans , 7 Autophagy , 176 Calcium/calmodulin-dependent protein kinase Axonopathies , 253 kinase β (CaMKKβ) , 15 , 194 Caloric restriction (CR) , 7 , 29 , 55 , 57 , 82 , 89 , 213 , 233 B anti-aging effects of , 218 Base excision repair (BER) , 157 , 182 Caloric restriction (CR)-induced insulin defect in human fi broblasts , 158 sensitivity , 200 BAT adipogenic program , 92 cAMP-responsive element binding-2 Bicyclic compound , 6 (CREB2) , 180 Biochemistry of sirtuins , 1–20 cAMP response element binding protein assays , 17–20 (CREB) , 73 , 86 Fluor de Lys fl uorescence assay , 17–18 Camptothecin , 180 mechanism-based affi nity capture of Cancer , 149 , 171–185 sirtuins , 20 analysis of human , 179 radioisotope assay , 19–20 cell metabolism , 172–176 SIRT1 fl uorescence polarization glucose metabolism , 172–174 assay , 19 glutamine metabolism , 174 , 175 defi nition , 1 lipid metabolism , 176 reactions and mechanisms , 4–7 cells , 162 , 176 reactivity , 2–4 crucial metabolic shift in , 174 SIRT1-7 regulation , 7–16 incidence , 171 by alterations in NAD metabolism , metabolism and sirtuins , 177–185 13–15 extramitochondrial sirtuins , 182 by compartmentalization , 15–16 mitochondrial metabolism , 177–178 by posttranslational modifi cation , SIRT1 , 183–184 11–12 SIRT2 , 185 by protein protein interactions , 12–13 SIRT3 regulates HIF1α stability , transcriptional regulation , 7–10 178–179 substrates , 3–5 SIRT4 , 179–181 Biogerontologists , 243 SIRT5 , 181 Biotin , 129 SIRT6 , 182–183 Biotin-carboxylase complex , 129 SIRT7 , 185 Biotin-dependent carboxylases , 129 mortality, disparity , 171 BMAL , 154 research on , 171 BMAL1 , 229 , 238 Cancerous mucosa , 255 Bmal1 −/− liver mitochondria , 233 Capillarization , 200 Bone marrow cells, SIRT6-defi cient , 152 Carbohydrate response element-binding Bovine serum albumin , 140 protein (ChREBP) , 73 Brain-derived neurotrophic factor Carbamoyl phosphate synthase 1 (CPS1) , 52 , (BDNF) , 154 59 , 142 , 181 , 244 Index 277 Carbohydrates , 172 , 193 Chronic heart disease (CHD) , 245 Carboxybiotin , 129 Chronic obstructive pulmonary disease Carboxylases , 129 (COPD) , 257 Carboxy terminal of E1A-binding protein Circadian clock , 229 (CtBP) , 8 clock-dependent changes in Cardiac hypertrophy , 160 metabolism , 232 Cardiomyocytes , 72 linking to NAD + metabolism , 234–237 Cardiomyocyte-specifi c Sirt6 KO mice , 161 sirtuins and , 230–234 Cardiovascular disease , 149 system , 229 Cardiovascular effects , 257 Circadian-dependent metabolism , 154 Casein kinase 2 (CK2) , 11 Circadian gene promoters , 236 Caspase 1 dependent mechanism , 91 Circadian locomotor output cycles kaput CCAAT/enhancer-binding protein (CLOCK) , 154 , 229 , 238 α (C/EBPα) , 10 Circadian machinery , 230 CD157 , 35 Circadian oscillation of NAD + , 236 CD38 , 14 , 35 , 37 , 75 , 84 Circadian oscillatory activity, AMPK , 235 Cell-autonomous defect , 151 Circadian rhythms , 229–230 Cell-autonomous tumor suppressor , 162 pharmacological modulation of , 237 , 238 Cell-based assays , 89 regulation of , 231 β-cells , 92–94 Citrate , 174 Cells Citrate synthase (CS) , 51 , 143 cancer , 162 , 176 c-JUN , 155 , 156 cycle regulation , 8 in absence of SIRT6 , 161 H3K56 acetylation in mammalian , 158 AP-1 component , 153 mammalian , 172 SIRT6 in modulating , 157 normal , 176 cJun N-terminal kinases (JNKs) , 11 proliferative cancer , 173 Classical non-homologous end-joining SIRT1-defi cient , 238 (C-NHEJ) , 158 SIRT6-defi cient , 157–159 , 162 Class III sirtuins , 140 SIRT6 in human , 159 Clock-controlled genes (CCG) , 229 Cellular acylome, mapping , 55–59 Clock-dependent lysine acetylation , 233 acetylation , 55–58 Clock machinery , 229 glutarylation , 59 Clock −/− mouse model , 233 succinylation , 58 , 59 Clock mutant ( ClockΔ19 ) mice , 230 Cellular metabolism , 95 , 179 14 C-nicotinamide , 6 reprogramming of , 174 Coactivator , 78 Central clock system , 229 Coactivator/corepressor complexes , 73 Central metabolic stress regulator , 221 Collagen-induced arthritis mouse model , 157 c-FOS signaling , 155 Colorectal cancers (CRCs) , 162 Chemical acetylation , 129 Complex II reductase , 120 Chemopreventive agent , 255 Core clock transcription machinery , 232 Cholesterogenic genes , 87 Corepressor , 78 Cholesterol gallstones , 217 Core transcription factors , 229 Cholesterol homeostasis , 88 Co-translational acetyl group transfer , 41 Cholesterol metabolism , 87 , 88 CREB regulated transcription coactivator-1 Chromatin , 149 (CRTC1) , 253 regulatory enzymes , 234 Crohn’s disease , 257 remodelers , 236 Crotonylation , 52 SIRT6 with , 155 Cryptochome ( Cry ), clock gene , 229 Chromatin-bound sirtuin , 182 Crystallography , 4 Chromatin-enriched nuclear HDAC , 233 C-terminal aminomethylcoumarin (AMC) Chromosome region maintenance 1 fl uorophore , 245 (CRM-1) , 16 C-terminal binding protein (CtBP) , 74 , 184 278 Index C-terminal GFP-SIRT5 , 139 E C-terminal V5-tagged SIRT5 , 139 Ectopically-expressed SIRT6 , 158 C-terminus , 18 , 19 Electron acceptor from ETC , 172 Cyclic ADP-ribose (cADPR) synthases , Electron transferring fl avoprotein (ETF) , 121 32 , 35 , 258 Electron transport chain (ETC) , 120 , 172 , 178 CyclinB/Cdk1 , 11 , 12 Electrophilic ADPR , 4 Cyclin-dependent kinase inhibitors , 202 Electrostatic facilitation mechanism , 125 Cyclin E/Cdk2 , 12 Embryonic cardiomyocytes , 16 Cyclophilin D (cypD) , 48 , 129 Embryonic fi broblasts , 72 CYP7A1 , 87 Endothelial NOS (eNOS) , 8 Cytochrome c , 142 Energetic stressor , 191 Cytokines , 90 Energy sensing proteins , 193 Cytoplasm , 106 , 156 , 192 Energy stress , 203 SIR-2.4 , 150 Enzymology of sirtuins , 1–20 Cytoplasmic sirtuin , 204 assays , 17–20 Cytosol , 32 , 47 , 53 , 73 Fluor de Lys fl uorescence assay , 17–18 Cytosolic fatty acids, chaperone for , 154 radioisotope assay , 19–20 Cytosolic MDH1 , 110 SIRT1 fl uorescence polarization assay , Cytosolic sirtuin , 185 1 9 Cytotoxic drug treatment , 12 defi nition , 1 mechanism-based affi nity capture of sirtuins , 20 D reactions and mechanisms , 4–7 Daf-16 mutant worms , 221 reactivity , 2–4 Deacetylate carbamoyl phosphate synthase-1 SIRT1-7 regulation , 7–16 (CPS1) , 181 by alterations in NAD metabolism , Deacetylated p53 , 8 13–15 Deacylases , 2 by compartmentalization , 15–16 Deacylation , 1 , 2 , 4 , 6 by posttranslational modifi cation , Deleted in breast cancer 1 (DBC1) , 12 , 13 , 78 , 11–12 83 , 89 , 184 by protein protein interactions , 12–13 Deletor mice , 36 transcriptional regulation , 7–10 Demalonylation , 181 substrates , 3–5 Dementia , 30 ERCs , 268 De novo biosynthesis , 14 ERR binding element (ERRE) , 10 De novo synthesis , 176 ES cells , 151 Dermatitis , 30 Escherichia coli ( E. coli ) , 50 , 51 Detection methods