Impaired metabolism of guanidinoacetic acid in uremia.
In order to investigate the guanidinoacetic acid (GAA) metabolism in uremia, we have measured serum guanidino compounds in patients with chronic renal failure (CRF) in comparison with normal subjects, and the renal content of GAA and glycine amidinotransferase (GAT) activity in the kidney of experimental CRF rabbits. Serum concentrations of guanidinosuccinic acid (GSA) and methylguanidine (MG) in the patients with CRF were higher than those in the normal subjects, as well as serum urea nitrogen (BUN) and creatinine (Cr) levels. The serum GAA levels were however, significantly lower and showed a tendency to decrease inversely with the elevation of BUN in the patients with CRF under conservative therapy. On the contrary, in the patients under maintenance hemodialysis (MHD) therapy, the serum GAA level did not decrease in spite of the elevation of BUN. Four anephric patients under MHD therapy showed a level of serum GAA similar to the other MHD patients. In the CRF rabbits, the renal GAA content was significantly lower than in the sham-operated rabbits and showed an inverse correlation with BUN. Renal GAT activity was also significantly lower in the CRF rabbits, showing a positive correlation with serum GAA concentration and an inverse correlation with BUN. These results indicate that renal GAT activity decreases as the BUN level rises in the course of renal damage, resulting in lower concentration of serum GAA in the uremic state; in a more advanced stage of renal failure, the inability of the kidney to synthesize GAA may be compensated by other organ(s). Some dialyzable substances which might inhibit renal GAT activity may also be present.
D000328:Adult; D000368:Aged; D000579:Amidinotransferases / Q000378:metabolism; D000818:Animals; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000378:metabolism; D006146:Guanidines / Q000097:blood; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011817:Rabbits; D006435:Renal Dialysis; D014511:Uremia / Q000378:metabolism* / Q000628:therapy
D006146:Guanidines; D000579:Amidinotransferases; C020681:glycine amidinotransferase; C004946:glycocyamine; D005998:Glycine