RT Book, Section
A1 Stockler-Ipsiroglu, Sylvia
A2 Kline, Mark W.
SR Print(0)
ID 1182928654
T1 Disorders of Creatine and Ornithine Metabolism
T2 Rudolph's Pediatrics, 23e
YR 2018
FD 2018
PB McGraw-Hill Education
PP New York, NY
SN 9781259588594
LK accesspediatrics.mhmedical.com/content.aspx?aid=1182928654
RD 2024/04/19
AB Creatine  is  both  ingested  in  the  diet  and  synthesized  mainly  in  the  liver  and  pancreas  by  the  action  of  arginine:glycine  amidinotransferase  (AGAT)  and  guanidinoacetate  methyltransferase  (GAMT),  with  arginine,  glycine,  and  S-adenosyl  methionine  as  essential  substrates  (Fig.  138-1).  AGAT  catalyzes  the  first  of  the  two  reactions  involved  in  the  de  novo  synthesis  of  creatine.  This  reaction  uses  arginine  and  glycine  as  substrates  and  yields  guanidinoacetate  and  ornithine  as  products.  Guanidinoacetate  is  further  converted  to  creatine  by  the  action  of  GAMT,  using  S-adenosylmethionine  as  a  methyl  group  donor,  with  this  reaction  consuming  a  significant  fraction  of  all  methyl  groups.  Creatine  reaches  muscle  and  brain  via  an  active  transmembrane  creatine  transport  system  (CRTR).  Creatine  is  then  used  in  the  cellular  pool  of  creatine/creatine-phosphate,  which  together  with  creatine  kinase  and  adenosine  triphosphate  (ATP)/adenosine  diphosphate  (ADP)  provides  a  high-energy  phosphate  buffering  system.  Intracellular  creatine  and  creatine  phosphate  are  nonenzymatically  converted  to  creatinine,  with  a  daily  turnover  rate  of  1.5%.  Creatinine  is  excreted  in  urine,  and  the  daily  urinary  creatinine  excretion  is  directly  proportional  to  total  body  creatine.