TY  - CHAP
M1  - Book, Section
TI  - Sickle Hemoglobin Polymerization
A1  - Kim-Shapiro, Daniel B.
A1  - Noguchi, Constance Tom
A1  - Schechter, Alan N.
A2  - Gladwin, Mark T.
A2  - Kato, Gregory J.
A2  - Novelli, Enrico M.
Y1  - 2021
N1  - 
T2  - Sickle Cell Disease
AB  - Sickle  cell  anemia  is  the  most  common  form  of  sickle  cell  disease  and  is  due  to  homozygosity  of  the  substitution  of  valine  for  glutamate  at  the  β6  position,  giving  rise  to  mutant  βS-globin  forming  sickle  hemoglobin  (HbS,  α2βS2).  Other  forms  of  sickle  cell  disease  include  hemoglobin  SC  disease  where  both  HbS  and  HbC  (caused  by  a  glutamate  to  lysine  substitution  at  the  β6  position  giving  rise  to  mutant  βC-globin)  coexist  and  HbS-β  thalassemia  (combination  of  1  mutant  βS-globin  gene  and  mutation  in  the  other  β-globin  gene  resulting  in  reduced  or  no  normal  β-globin  production).  In  all  these  cases,  the  dysfunction  of  HbS  is  the  primary  cause  of  the  disease.  Almost  all  of  the  major  physiologic  properties  of  HbS  in  dilute  solution  (eg,  oxygen,  carbon  dioxide,  2,3-diphosphoglyceric  acid  [DPG],  and  hydrogen  ion  binding,  as  well  as  the  cooperativity  of  oxygen  binding)  are  normal.  However,  the  low  solubility  upon  deoxygenation  of  HbS,  as  compared  to  the  very  high  solubility  of  the  deoxy  form  of  HbA  (α2β2),  at  the  high  concentrations  inside  the  red  cell,  causes  aggregation  of  the  hemoglobin  molecules,  which  is  the  major  direct  effect  of  the  sickle  mutations  (βSGlu6→Val).  We  assume  that  abnormal  red  cell  flow  properties  in  the  circulation  and  the  accompanying  increase  in  hemolysis  and  thus  all  clinical  manifestations  can  be  traced  back  to  this  phenomenon.  The  major  factors  affecting  the  effective  solubility  inside  the  red  cell  are  the  intracellular  hemoglobin  composition  and  concentration  and  the  oxygen  saturation,  whereas  other  cellular  variables  have  smaller  effects  (see  Figure  2-1  for  overview  of  this  paradigm).  
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/18
UR  - hemonc.mhmedical.com/content.aspx?aid=1179337962
ER  -