Ureotelic animals

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). 

Ureotelic animals many terrestrial vertebrates also sharks... 

Birds and reptiles are oviparous, and the cleidoic eggs that they produce contain all the nutrient required until hatching. This nutrient, which is mainly protein and lipoprotein, is synthesised in the liver and oviduct prior to oviposition. Lipoproteins are discussed in Section 4.5, and the control of egg protein synthesis in Section 10.3. Birds excrete a semi-solid urine, and this requires a lower water intake than is possible in ureotelic animals. The metabolic adaption that allows this to occur is the excretion of nitrogen principally in the form of uric acid. Uric acid is sparingly soluble in water and is present in avian ureters largely as a colloidal suspension. This is discussed in Section 5.4. 

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 end products of purine metabolism are uric acid in primates and uricotelic animals, allantoin in mammals other than primates, urea in the rest of the ureotelic animals, and ammonia in many of the ammonotelic animals. 

Liver of true ureotelic animals (see 401a) contmns the enzyme carbamyl phosphate synthetase which catalyzes the following reaction (2, 402) ... 

The binding of NH<+ by the enzyme is inhibited by Na+ In the presence of a K+ medium, the affinity of carbamyl phosphate synthetase for NH4+ is increased several-fold at low NH4+ concentration (10 -10 M) (406). This fact is of considerable physiological significance since it reveals the ability of this enzyme system to operate efficiently in an intracellular medium at the low intracellular NH4+ concentrations known to exist in liver of mammals (4O8, 409). A potent antibody has been produced to the frog liver enzyme by immunization of the rabbit and goat (410). A remarkable feature of the antibody is its ability to cross-react with extracts of livers of other ureotelic animals, but not with extracts of livers from non-ureotelic animals (410). The enzyme is inactive at the equivalence zone (410). 

Ornithine transcarbamylase has been found to occur in microorganisms S90, S96-401, 418), plants 419-421), yeast 422), and liver 404, 417, 423-429) and intestine 4II) of ureotelic animals. The enzyme has been partially purified from beef liver 417, 423), frog liver 406), E. coli 431), and Streptococcus lactis 4I8). Ornithine transcarbamylase shows a high substrate specificity 417, 423). The synthesis of the enz3nne is suppressed by arginine in E. coli 430, 431). 

The enzyme is present in high concentration in the liver of all ureotelic animals, and is also present, but in much lower amounts, in kidney of all animals (451, 453, 454). The enzyme is present in most organs of the shark... 

The enzymes discussed in the previous sections (carbamyl phosphate synthetase, ornithine transcarbamylase, argininosuccinate synthetase, cleavage enzyme, and arginase) constitute the known enzymic steps in the sequence of reactions leading to the biosynthesis of urea in ureotelic animals in accordance with the cycle originally proposed by Krebs and Hen-seleit (458). A summary scheme showing the steps in this cycle and the relationship of some of the intermediates to other systems is shown in Fig. 2. 

The ornithine cycle in the ureotelic animal is irreversible under... 

Transformation and Degradation of Purine in Animals.—Animals other than birds and reptiles excrete their waste protein nitrogen in the urine, and are said to be ureotelic. In ureotelic animals, purine metabolism proceeds along independent lines. The purines of the diet, chiefly nucleotides and nucleosides liberated from nucleo-proteins, are resolved into their constituent amino purines by the enzymes of the alimentary tract and mucosa. The amino purines are absorbed into the portal s3rstem, and if not utilised, are de-aminated by the appropriate enzjones, adenase and guanase, found in the liver. 

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. 

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 ... 

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. 

Most of the animals listed in Table lO-I are ureotelic or ammoniotelic i.e., urea or ammonia is the chief end product of protein metabolism. Birds,... 

In addition to the requirement for pyrimidine nucleotide synthesis, carbamyl phosphate is required for synthesis of arginine and urea. Carbamyl phosphate synthesis is a prominent activity in ureotelic liver and is aimed primarily at the formation of urea the process of urea synthesis is served by a special carbamyl phosphate synthetase which is quite distinct from the enzymes responsible for carbamyl phosphate synthesis in extrahepatic tissues and in the livers of uricotelic animals. A third mechanism for synthesis of carbamyl phosphate is found in bacteria. 

Arginase occurs in the livers of all animals that are ureotelic in that they excrete their waste nitregen chiefly in the form of urea. It is absent from the livers of uricotelic animals (birds and most reptiles), which excrete nitrogen as uric acid. Traces of the enzyme may occur in non-hepatic tissue, and it has also been identified in plants. 

In terms of amino nitrogen excretion the animal kingdom can be classified into ammonotelic (ammonia), ureotelic (urea) and uricotelic (uric acid) organisms depending on the nature of the discharged substance. 

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