TY  - CHAP
M1  - Book, Section
TI  - Erythrocyte Enzyme Disorders
A1  - van Solinge, Wouter W.
A1  - van Wijk, Richard
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  - SUMMARYRed  cells  possess  active  metabolic  machinery  that  provides  energy  to  pump  ions  against  electrochemical  gradients,  to  maintain  red  cell  shape,  to  keep  hemoglobin  iron  in  the  reduced  form,  and  to  maintain  enzyme  and  hemoglobin  sulfhydryl  groups.  The  main  source  of  metabolic  energy  comes  from  glucose.  Glucose  is  metabolized  through  the  glycolytic  pathway  and  through  the  hexose  monophosphate  shunt.  Glycolysis  catabolizes  glucose  to  pyruvate  and  lactate,  which  represent  the  end  products  of  glucose  metabolism  in  the  erythrocyte,  because  it  lacks  the  mitochondria  required  for  further  oxidation  of  pyruvate.  Adenosine  diphosphate  (ADP)  is  phosphorylated  to  ATP,  and  nicotinamide  adenine  dinucleotide  (NAD)+  is  reduced  to  NADH  in  glycolysis.  2,3-Bisphosphoglycerate,  an  important  regulator  of  the  oxygen  affinity  of  hemoglobin,  is  generated  during  glycolysis.  The  hexose  monophosphate  shunt  oxidizes  glucose-6-phosphate,  reducing  NADP+  to  reduced  nicotinamide  adenine  dinucleotide  phosphate  (NADPH).  In  addition  to  glucose,  the  red  cell  has  the  capacity  to  utilize  some  other  sugars  and  nucleosides  as  a  source  of  energy.  The  red  cell  lacks  the  capacity  for  de  novo  purine  synthesis,  but  has  a  salvage  pathway  that  permits  synthesis  of  purine  nucleotides  from  purine  bases.  The  red  cell  contains  high  concentrations  of  glutathione,  which  is  maintained  almost  entirely  in  the  reduced  state  by  NADPH  through  the  catalytic  activity  of  glutathione  reductase.  Glutathione  is  synthesized  from  glycine,  cysteine,  and  glutamic  acid  in  a  two-step  process  that  requires  ATP  as  a  source  of  energy.  Catalase  and  glutathione  peroxidase  serve  to  protect  the  red  cell  from  oxidative  damage.  The  maturation  of  reticulocytes  into  erythrocytes  is  associated  with  a  rapid  decrease  in  the  activity  of  several  enzymes.  However,  the  decrease  in  activities  of  other  enzymes  occurs  much  more  slowly  or  not  at  all  with  aging.Erythrocyte  enzyme  deficiencies  may  lead  to  hemolytic  anemia;  expression  of  the  defect  in  other  cell  lines  may  lead  to  pathologic  changes  such  as  neuromuscular  abnormalities.  Glucose-6-phosphate  dehydrogenase  (G6PD)  deficiency  is  the  most  common  erythrocyte  enzyme  defect.  In  some  populations,  more  than  20  percent  of  people  may  be  affected  by  this  enzyme  deficiency.  In  the  common  polymorphic  forms,  such  as  G6PD  A–,  G6PD  Mediterranean,  or  G6PD  Canton,  hemolysis  occurs  only  during  the  stress  imposed  by  infection  or  administration  of  “oxidative”  drugs,  and  in  some  individuals  upon  ingestion  of  fava  beans.  Neonatal  icterus,  which  appears  largely  with  the  interaction  with  an  independent  defect  in  bilirubin  conjugation,  is  the  clinically  most  serious  complication  of  G6PD  deficiency.  Patients  with  uncommon,  functionally  very  severe,  genetic  variants  of  G6PD  experience  chronic  hemolysis,  a  disorder  designated  hereditary  nonspherocytic  hemolytic  anemia.Hereditary  nonspherocytic  hemolytic  anemia  (HNSHA)  also  occurs  as  a  consequence  of  other  enzyme  deficiencies,  the  most  common  of  which  is  pyruvate  kinase  (PK)  deficiency.  Glucose  phosphate  isomerase  (GPI),  triosephosphate  isomerase  (TPI),  and  pyrimidine  5′-nucleotidase  (P5′N)  deficiency  are  included  among  the  relatively  rare  causes  of  hereditary  nonspherocytic  hemolytic  anemia.  In  the  case  of  some  deficiencies,  notably  those  of  glutathione  synthetase  (GS),  TPI,  and  phosphoglycerate  kinase  (PGK),  the  defect  is  expressed  throughout  the  body,  and  neurologic  and  other  defects  may  be  a  prominent  part  of  the  clinical  syndrome.Diagnosis  is  best  achieved  by  determining  red  cell  enzyme  ...
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PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/16
UR  - hemonc.mhmedical.com/content.aspx?aid=1121093547
ER  -