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UREA: DIVERSE FUNCTIONS OF A ‘WASTE” PRODUCT
Author(s) -
Withers Philip C.
Publication year - 1998
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1998.tb02284.x
Subject(s) - urea , biology , lungfish , urea cycle , hagfish , osmolyte , aestivation , arginase , biochemistry , zoology , glutamine , arginine , vertebrate , amino acid , fish <actinopterygii> , fishery , gene
SUMMARY 1. The urea cycle is essentially the simultaneous operation of two linear pathways, both primitive and widespread among animals; one is for arginine synthesis and the other is for arginine degradation to ornithine and urea. 2. All animals may have the genetic capacity to express a urea cycle and many diverse groups of animals, from flatworms to mammals, have a functional urea cycle. 3. Evolutionary changes in vertebrates of carbamyl‐phosphate synthetase (CPS) are directed from glutamine‐dependent (CPSIII) towards NH 3 ‐dependent (CPSI) ureagenesis. Invertebrates, cartilagenous fish and the coelacanth have CPSIII (i.e. glutamine‐dependent), whereas lungfish, amphibians and amniote vertebrates have CPSI; the teleost Heteropneustes has CPSI‐like activity. That the coelacanth has CPSIII and Heteropneustes has ‘CPSI’ suggests that the form of CPS may by physiologically related (CPSIII in a balancing solute role and CPSI in a terrestrial, air‐breathing excretion role) rather than being phylogenetically constrained. 4. Urea is a major balancing osmolyte in marine cartilagenous fish, the coelacanth and a few amphibians and some aestivating terrestrial amphibians. It is a storage osmolyte in cocoon‐forming aestivating lungfish and amphibians. 5. Urea contributes towards positive buoyancy in marine cartilagenous fish. 6. Urea functions for non‐toxic N transport in ruminant and pseudoruminant mammals 7. Urea is a major solute in the mammalian (but not avian) kidney, contributing to a renal medullary osmotic gradient; it is substantially reabsorbed by mammalian nephrons. 8. Urea is used as a preferred nitrogenous waste compared with ammonia at high ambient pNH 3 or pH, with water restriction, or air breathing. 9. Urea synthesis maintains acid‐base balance by the 1:1 stoichiometry of removal of HCO 3 − and NH 4 + .