Uricotelic

Ammonia (NH3) is a relatively strong base, and at physiological pH values it is mainly present in the form of the ammonium ion NH4 (see p. 30). NH3 and NH4 are toxic, and at higher concentrations cause brain damage in particular. Ammonia therefore has to be effectively inactivated and excreted. This can be carried out in various ways. Aquatic animals can excrete NH4 directly. For example, fish excrete NH4 via the gills (ammonotelic animals). Terrestrial vertebrates, including humans, hardly excrete any NH3, and instead, most ammonia is converted into urea before excretion ureotelic animals). Birds and reptiles, by contrast, form uric acid, which is mainly excreted as a solid in order to save water uricotelic animals). 

Excess nitrogen is excreted as ammonia. Ammonotelic organisms excrete ammonia directly, uricotelic organisms excrete it as uric acid, and ureotelic organisms excrete it as urea. 

Uric acid, the major nitrogenous waste product of uricotelic organisms, is also formed in other organisms from the breakdown of purine bases. Gout is caused by the deposition of excess uric acid crystals in the joints. 

Uric acid (Fig. 6) is the main nitrogenous waste product of uricotelic organisms (reptiles, birds and insects), but is also formed in ureotelic organisms from the breakdown of the purine bases from DNA and RNA (see Topics FI and Gl). Some individuals have a high serum level of sodium urate (the predominant form of uric acid at neutral pH) which can lead to crystals of this compound being deposited in the joints and kidneys, a condition known as gout, a type of arthritis characterized by extremely painful joints. 

In humans and many other vertebrates, ammonia arising from deamination reactions or other sources is excreted in the form of urea. These animals are called ureo-telic. Fish excrete nitrogen in the form of ammonium ions and are therefore ammonotelic. Animals that need to conserve water excrete their nitrogen in the form of crystalline uric acid. They are uricotelic, or purinotelic. One often finds animals that convert uric acid to allantoin via uric acid oxidase (Figure 20.8). Allan-toin is more water soluble than uric acid. Uric acid oxidase is absent from primates. 

Primates, birds uricotelic reptiles, insects (other than diptera)... 

Both ureotelic and uricotelic animals form uric add, but in the former it is only derived fi-om purine catabolism. In uricotelic animals, such as birds, uric add formation assumes much greater importance. 

Rat liver apparently contains a serine hydroxymethyltransferase in the cytosol and another inside the inner membrane of the mitochondria. The two enzymes have different properties (Palekaref al., 1973). The concerted operation of serine hydroxymethyltransferase in the cytosol with the conversion of glycine to serine in mitochondria of liver probably forms the main mechanisms for catabolism of glycine (Kikuchi, 1973 Cybulski and Fisher, 1976). In ureotelic animals the C, produced is oxidized to CO2 whereas in birds and other uricotelic animals Ci is needed with glycine for synthesis of uric acid. Extramitochondrial serine hydroxymethyltransferase in plants may be needed for synthesis of glycine, serine, and active Ci but may serve a catabolic function also. 

The Km for IMP is usually fairly low for the biosynthetic acidic isozyme and the bacterial enzyme, and higher for the muscle enzyme. Both the muscle and liver enzymes of the chick have low fiCmS for aspartate. This may relate to the uricotelic nature of this species. 

Carbamoyl phosphate synthesis from ammonia represents one of the prominent activities in ureotelic livers [78]. The enzyme requires N-acetylglutamate and is distinct from the enzyme responsible for carbamoyl phosphate synthesis in extrahepatic tissues and in the livers of uricotelic animals. This second enzyme utilizes glutamine [79], rather than ammonia as the primary nitrogen donor and is found in mushrooms, Escherichia coli, yeast, Ehrlich ascites tumour and several other animal tissues [80]. This enzyme is carbamoyl phosphate synthetase II (ATP carbamate phosphotransferase, EC 2.7.2.2) and catalyses the following reaction ... 

Ureoteles and uricoteles use pre-existing, very ancient biochemical mechanisms for nitrogen excretion urea synthesis by the urea cycle, which first evolved for the synthesis and degradation of arginine and... 

There is a striking correlation between the form of nitrogen excretion and the pathway used by an animal to deaminate amino acids arising from proteolysis in ureoteles amino acids are transaminated with 2-oxo-glutarate to form glutamate, which in turn is attacked hy glutamate dehydrogenase, whereas in uricoteles amino acids are attack by amino acid oxidases. 

---