Journal
KIDNEY INTERNATIONAL
Volume 59, Issue -, Pages S102-S107Publisher
ELSEVIER SCIENCE INC
DOI: 10.1046/j.1523-1755.2001.59780102.x
Keywords
cyanate; urea; carbamoyl-amino acids; uremic toxin
Categories
Funding
- NIDDK NIH HHS [DK37763] Funding Source: Medline
Ask authors/readers for more resources
Cyanate spontaneously transformed from urea increases as renal function decreased. Acting as a potential toxin, the active form of cyanate, isocyanic acid, carbamoylates amino acids, proteins, and other molecules, changing their structure, charge, and function. The resulting in vivo carbamoylation can modify the molecular activity of enzymes, cofactors, hormones, low-density lipoproteins, antibodies, receptors, and transport proteins. Antibodies specific for epsilon -amino-carbamoyl-lysine (homocitrulline) located carbamoylated proteins in situ in neutrophils, monocytes, and erythrocytes. Carbamoylated proteins were found in renal tissue from uremic patients but not in normal transplanted kidneys. The irreversible reaction with cyanate converts free amino acids (F-AAs) to carbamoyl-amino acids (C-AAs). The Carbamoylation Index(CI), C-AA/F-AA, quantifies the decrease of the F-AA pool for each essential amino acid. C-AAs contribute, in part, to malnutrition of uremia. C-AAs interfered with protein synthesis to lower C-14 hemoglobin synthesis in human reticulocytes and osteocalcin synthesis in rat osteosarcoma-derived tissue culture. Insulin-sensitive glucose uptake was decreased 33% in cultured rat adipocytes by alpha -amino-carbamoyl-asparagine. alpha -Amino carbamoylation occurs primarily in F-AA, while epsilon -amino carbamoylation of lysine in protein occurs continuously during the protein lift: span. Protein catabolism releases epsilon -amino-carbamoyl-lysine. Quantitation of alpha versus epsilon carbamoylation may yield a more sensitive measurement of protein intake versus protein catabolism, and could be useful in decisions concerning the time to initiate dialysis or subsequent changes in dialysis prescription. Carbamoylated molecules can block, enhance, or be excluded from metabolic pathways, thereby influencing the fate of noncarbamoylated molecules. Although not an all-or-none phenomenon, urea-derived cyanate and its actions are contributing causes of toxicity in uremia.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available