Ornithine cycle

Kestens, P.J. (1964). La Perfusion du Foie Isole. Editions Arscia S.A. Bruxelles. Meyer, AJ. Lamers, W.H., Chamulead, R.A.F.M. (1990). Nitrogen metabolism and ornithine cycle fixation. Physiol. Rev. 70, 701-748. 

Isotopic dilution of urea Urea is synthesised continually from carbon dioxide and ammonia in the body, in the ornithine cycle... 

The concept of the ornithine cycle arose from the observation that ornithine, citrulline and arginine stimulated urea production in the presence of ammonia without themselves being consumed in the process. 

Ammonia is generated mainly from the metabolism of amino acids and from the catabolism of purine and pyrimidine bases, which are produced from nucleic acids. Since it is toxic, it must be converted to a non-toxic compound for excretion from the body. This is achieved via the ornithine cycle, more usually known as the urea cycle. 

The carbamoyl phosphate synthetase (abbreviated to CPS-I) that is involved in the ornithine cycle differs from the enzyme that is involved in pyrimidine synthesis (carbamoyl phosphate synthetase-ll). The latter enzyme is cytosolic, requires glutamine for provision of nitrogen, rather than ammonia, and is regulated by different factors (Chapter 20). 

Consequently, as with some other processes, the physiological ornithine cycle spans more than one tissue. An hypothesis put forward to account for the regulation of the cycle must take into account the snpply of ammonia for conversion to urea. The approach used to formulate a theory of regulation is described in Chapter 3. 

The liver is unusual in that it receives blood from two sources, the hepatic artery and the hepatic portal vein. The two supplies eventually join at the central vein, hence hepatocytes are of two types those which are exposed to blood derived largely from the hepatic artery, known as the perivenons cells, and those that are exposed to blood largely from the portal vein which are known as periportal cells (see Chapter 8). The periportal hepatocytes contain the enzymes of the ornithine cycle. In contrast, the... 

In the urea cycle, two molecules of ammonia combine with a molecule of carbon dioxide to produce a molecule of urea and water. The overall cycle involves a series of biochemical reactions dependent on enzymes and carrier molecules. During the urea cycle the amino acid ornithine (C5H12N202) is produced, so the urea cycle is also called the ornithine cycle. A number of urea cycle disorders exist. These are genetic disorders that result in deficiencies in enzymes needed in one of the steps in the urea cycle. When a urea cycle deficiency occurs, ammonia cannot be eliminated from the body and death ensues. 

Fig. 6.11. The (Krebs-Henseleit) ornithine cycle. Numbers refer to enzymes as follows. (1) Carbamyl phosphate synthetase (E.C.2.7.2.a). (2) Ornithine transcarbamylase (E.C.2.1.3.3). (3) Arginino-succinate synthetase (E.C.6.3.4.5). (4) Arginino-succinate lyase (E.C.4.3.2.1). (5) Arginase (E.C.3.5.3.1). (After Smyth, 1969.)...

F.L. Holmes. 1980. Hans Krebs and the discovery of the ornithine cycle Fed. Proc. 39 216-225. (PubMed)... 

Fig. 3.12 Diagram showing the ammonia detoxification process in the urea cycle (= ornithine cycle) (H.A. Krebs, K. Henseleit, 1932) (A.L. Lehnesigee, 1979)...

The urea cycle, also called ornithine cycle, was first described by H.A. Krebs and K. Henseleit in 1932. (quot. 51) The principle of ammonia detoxification in the urea cycle is based on the conversion of ammonium and bicarbonate in the mitochondria under ATP consumption into carbamoyl phosphate (by means of carbamoyl phosphate synthetase). It enters the urea cycle, which is localized mainly - yet with a low affinity for ammonium - in the periportal zone of the liver lobule. In the urea cycle alone, about two thirds of the amino nitrogen of ammonia are irretrievably lost to the organism (= definitive ammonia detoxification), (s. fig. 3.12)... 

Takiguchi, M., and Mori, M. (1995). Transcriptional regulation of genes for ornithine cycle enzymes. Biochem.. 312, 195-205. 

Sen [1839-1841] further suggested that the ammonia formed enters the ornithine cycle and that the phosgene creates uraemic coma (although he offers no rationalization for this suggestion). On both chemical and medical grounds, these papers merit no serious consideration. 

C5. Cedrangolo, F., Della Pietra, G., De Lorenzo, F., Papa, S., and Cittadini, D., The effect of a-D,L-methylaspartate on ornithine cycle reactions and urea excretion in rats. Emymologia 25, 308-314 (1963). 

Kuhn NJ, Ward S, Piponski M, et al. 1995. Purification of human hepatic arginase and its manganese (Il)-dependent and pH-dependent interconversion between active and inactive forms A possible pH sensing function of the enzyme on the ornithine cycle. Arch Biochem Biophys 320 24-34. 

The ornithine cycle [Eq. (8)-(ll)] was proposed by Krebs and Henseleit (1932) to explain urea formation from ammonium derived from amino acid catabolism in the mammalian liver. Since the promulgation of the ornithine cycle was partly based on the natural occurrence of citrulline in juice of the watermelon Citrullus vulgaris) (Wada, 1930), it is not surprising that citrulline is an intermediate in arginine formation in higher plants. 

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