TY  - CHAP
M1  - Book, Section
TI  - Metabolism of Hematologic Neoplastic Cells
A1  - Walton, Zandra E.
A1  - Hsieh, Annie L.
A1  - Dang, Chi V.
A2  - Kaushansky, Kenneth
A2  - Lichtman, Marshall A.
A2  - Prchal, Josef T.
A2  - Levi, Marcel M.
A2  - Press, Oliver W.
A2  - Burns, Linda J.
A2  - Caligiuri, Michael
PY  - 2015
T2  - Williams Hematology, 9e
AB  - SUMMARYThe  quantum  physicist  Erwin  Schrodinger  surmised  in  his  monograph  “What  is  Life?”  that  the  organized  matter  known  as  life  needs  to  feed  on  “negative  entropy”  to  avoid  decay.1  He  concluded  that  this  feeding  on  negative  entropy  is  achieved  through  metabolism,  a  term  derived  from  Greek  that  describes  an  exchange  of  materials.  Because  of  this  centrality  to  life,  metabolism’s  core  pathways—glycolysis  and  respiration—evolved  early  in  Earth’s  history  and  are  highly  conserved.  At  every  stage  of  life,  metabolism  provides  the  needed  nutrients,  energy,  and  building  blocks.  Embryogenesis,  for  instance,  requires  metabolism  of  maternally  derived  nutrients  to  support  cellular  repair,  growth,  division,  and  differentiation.  In  particular,  cell  replication  requires  that  the  instructions  emanating  from  the  DNA  sequence,  modulated  by  the  epigenome,  couple  with  the  import  of  nutrients  and  metabolic  pathways  to  produce  the  components  and  energy  necessary  to  build  two  copies  of  a  cell  and  maintain  high  replication  fidelity  of  the  genome.  During  growth  and  development,  and  especially  during  adulthood,  metabolism  also  plays  the  important  role  of  providing  bioenergetics  for  cellular  and  organismal  homeostasis.  Metabolism  can  also  feature  prominently  in  disease,  and  this  chapter  discusses  how  the  metabolic  pathways  central  to  life  and  normal  biology  can  be  subverted  in  cancer  to  fuel  abnormal  growth.Food,  through  metabolism,  provides  the  nutrients  necessary  for  homeostasis,  repair,  and  reproduction  of  many  organisms.  To  align  supply  and  demand,  mammalian  metabolism  is  linked  to  sleep  cycles  through  the  central  circadian  clock  that  senses  light  and  dark  phases  of  the  day  via  the  eye  and  central  nervous  system.  The  central  regulation  of  feeding  and  sleeping  cycles  coordinates  nutrient  availability  from  food  with  the  circadian  oscillation  of  metabolism  of  individual  cells,  which  all  have  a  molecular  clock  comprised  of  a  network  of  transcription  factors  that  regulates  cell  metabolism.2Food  is  digested,  absorbed  through  the  gastrointestinal  tract,  and  in  part  processed  or  stored  in  the  liver,  which  is  a  key  metabolic  organ.3  Processed  lipids  in  the  form  of  lipoproteins  are  synthesized  in  the  liver  and  disseminated  throughout  to  supply  the  needs  of  various  organs.  Amino  acids,  with  glutamine  circulating  at  the  highest  level  (0.5  mM),  supply  cells  with  building  blocks  for  proteins.  Some  amino  acids  (nonessential)  are  synthesized  by  humans,  but  essential  amino  acids  must  be  available  from  the  diet.  Complex  carbohydrates  are  broken  down  and  circulate  as  glucose,  a  vital  nutrient  for  virtually  all  mammalian  cells.  In  this  regard,  an  endocrine  system  (insulin  and  glucagon)  has  evolved  to  control  the  circulating  levels  of  this  precious  bioenergetic  molecule.  When  in  excess,  amino  acids  and  sugars  contribute  to  lipogenesis,  and  the  extra  energy  is  stored  as  fat  depots  in  adipose  tissues.  Excess  glucose  is  stored  as  glycogen,  which  is  deployed  to  release  glucose  in  starved  conditions.  It  is  believed  that,  during  our  evolution,  periods  of  gorging  and  feeding  were  separated  by  significant  durations  of  starvation;  hence,  we  have  evolved  mechanisms  to  survive  starvation.In  contrast  to  the  fed  state,  when  insulin  level  increases  in  response  to  rising  glucose  to  trigger  cellular  glucose  uptake  and  storage,  the  starved  state  triggers  glucagon  secretion  from  the  pancreas,  which  mobilizes  cellular  ...
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/16
UR  - accessmedicine.mhmedical.com/content.aspx?aid=1121089498
ER  -