RT Book, Section
A1 Semenza, Giorgio
A1 Auricchio, Salvatore
A1 Mantei, Ned
A2 Valle, David L.
A2 Antonarakis, Stylianos
A2 Ballabio, Andrea
A2 Beaudet, Arthur L.
A2 Mitchell, Grant A.
SR Print(0)
ID 1181421417
T1 Small-Intestinal Disaccharidases
T2 The Online Metabolic and Molecular Bases of Inherited Disease
YR 2019
FD 2019
PB McGraw-Hill Education
PP New York, NY
SN 9780071459969
LK ommbid.mhmedical.com/content.aspx?aid=1181421417
RD 2024/04/19
AB The  brush-border  membrane  of  the  human  small  intestine  is  endowed  with  a  total  of  seven  glycosidases,*  which  give  rise  to  free  monosaccharides  by  splitting  dietary  disaccharides  and  oligosaccharides  that  arise  in  the  intestinal  lumen  from  the  α-amylolysis  of  starch.  The  four  “maltases”  occur  as  two  heterodimers  (i.e.,  the  glucoamylase  complex  and  the  sucrase-isomaltase  complex);  the  β-glycosidase  complex,  which  is  composed  of  a  single  type  of  polypeptide,  has  two  catalytic  sites  (lactase  and  glycosylceramidase).  Trehalase  is  composed  of  a  single  type  of  subunit(s)  (Table  96–1).  These  glycosidases  are  stalked  intrinsic  proteins  of  the  membrane;  the  body  of  the  protein  mass,  including  the  catalytic  sites,  protrudes  toward  the  small-intestinal  lumen.The  glycosidases,  with  the  exception  of  trehalase,  are  synthesized  as  very  large  polypeptide  chains,  each  of  which  has  an  apparent  molecular  weight  in  the  range  of  200,000  to  250,000.  These  pro  forms  are  each  split  into  the  final  forms  either  extracellularly  (as  are  the  α-glucosidase  complexes)  or  mostly  intracellularly  (the  β-glycosidase  complex;  see  Table  96–2).  Since  the  two  catalytic  domains  in  each  of  these  complexes  belong  to  a  single  translational  unit,  they  are  subject  to  the  same  biologic  control  mechanism(s).Mammals  other  than  humans  are  equipped  at  birth  with  the  β-glycosidase  and  the  glucoamylase  complexes.  Sucrase-isomaltase  and  trehalase  develop  at  the  time  of  weaning,  when  the  β-glycosidase  complex  begins  to  decline,  eventually  reaching  a  level  as  low  as  5  to  10  percent  of  that  at  birth.  In  contrast,  in  humans,  the  brush-border  disaccharidases  develop  before  birth,  beginning  prior  to  week  10  of  gestation,  with  a  developmental  burst  (particularly  in  the  β-glycosidase  complex)  a  few  weeks  before  birth.  The  level  of  the  β-glycosidase  complex—in  effect,  the  level  of  lactase  activity—remains  high  throughout  adulthood  in  most  white  people  and  a  few  other  races.The  primary  site  of  control  in  the  spontaneous  physiological  development  of  sucrase-isomaltase  is  in  all  likelihood  at  the  level  of  transcription.  Dietary  and  hormonal  factors  also  control  the  levels  of  disaccharidase  activities.Both  secondary  and  primary  (genetic)  disaccharidase  deficiencies  are  known,  which  may  lead  to  malabsorption  and  intolerance  of  the  corresponding  disaccharide(s)  but  not  of  the  constituent  monosaccharides.  Diagnosis  depends  on  determination  of  enzyme  activities  through  small-intestinal  biopsies  and/or  on  an  oral  tolerance  test  with  the  corresponding  disaccharides.  Among  the  latter,  the  breath  hydrogen  test  is  particularly  reliable.All  genetic  variants  of  intestinal  disaccharidases  are  monofactorial  and  autosomal.  The  most  common  polymorphic  variant  is  adult-type  hypolactasia,  in  which  intestinal  lactase  declines  in  childhood  or  shortly  thereafter  to  10  percent  or  less  of  the  level  at  birth.  It  should  be  considered  the  normal  situation,  since  it  occurs  in  the  majority  of  human  populations  (and  in  essentially  all  mammals  other  than  humans).  The  genetic  basis  of  human  adult-type  hypolactasia  is  discussed  in  Genetic  Polymorphism  of  Intestinal  Lactase  Activity  in  Adult  Humans.Sucrase-isomaltase  deficiency  is  much  rarer  and  is  also  genetically  heterogeneous.Congenital  lactase  deficiency  and  trehalase  deficiency  are  very  rare,  and  little  is  known  about  their  molecular  basis.