Ornithine metabolism, arginine synthesis

Fig. 4. Outline of synthetic and degradative pathways of arginine and proline in plant cells. This figure emphasizes the synthetic and degradative aspects of arginine and proline metabolism. Protein is considered the end-product of synthesis and the starting point of degradation. Compounds on both sides of center line are considered to be in separate pools (possibly separated by membranes). Subscript "ex refers to ornithine supplied from outside the cell. The dotted arrows indicate that,a small proportion of the ornithine metabolized goes to KAV. Abbreviations not explained in the legend to Fig. 3 are as follows AcGLU, acetylglutamic acid AcORN, acetylornithine.

The enzymes of the urea cycle, however, are not only expressed in the liver, but also in other tissues and cell types. In fact, it is believed that the urea cycle evolved from the arginine metabolic pathway present in lower organisms (Takiguchi et al, 1989). This difference in function between urea and arginine synthesis is reflected by the different tissue localization, function and regulation of the enzymes of the urea cycle and other enzymes involved in the metabolism of the urea cycle intermediates, arginine, citrulline and ornithine. 

Figure 31-3. Arginine, ornithine, and proline metabolism. Reactions with solid arrows all occur in mammalian tissues. Putrescine and spermine synthesis occurs in both mammals and bacteria. Arginine phosphate of invertebrate muscle functions as a phosphagen analogous to creatine phosphate of mammalian muscle (see Figure 31-6).

As early as 1932, H.A. Krebs and K. Henseleit established that of the investigated amino acids, only ornithine was able to effect a real increase in the synthesis of urea from ammonia (although arginine also displayed low efficacy), (quot. 57) Thus it seemed possible to raise the turnover of ammonia in the metabolism process by using intermediates of the urea cycle. (127) (s. tab. 15.6) (s. fig. 3.10) To this end, ornithine aspartate (oral and parenteral route), arginine malic... 

There are small but significant alterations in the plasma levels of two of the amino acids involved in the urea cycle. Both citrulline and arginine levels are low, about one-third to one-half the normal levels (Lll) sometimes even lower (Table 6). These changes would be expected since these acids are in the metabolic pathway beyond the block. What appears surprising is that the level of ornithine, the amino acid whose further metabolism is blocked, which would be expected to rise, is actually usually within normal limits. There are two possible explanations for this. The biosynthesis of urea forms a cycle in which each intermediate is re-formed in the process. The block in the synthesis of citrulline from ornithine results in a decreased formation of arginine which in turn will... 

Several standard and nonstandard amino acids act as metabolic intermediates. For example, arginine, citrulline, and ornithine (Figure 5.6) are components of the urea cycle (Chapter 15). The synthesis of urea, a molecule formed in vertebrate livers, is the principal mechanism for the disposal of nitrogenous waste. 

The first M.c. to be recognized was the Urea cycle (see), described by Krebs and Henseleit in 1932. This may be considered as an anabolic cycle since it results in the energy-dependent synthesis of urea but with respect to its metabolic role in the degradation of protein and detoxication of ammonia, it is catabolic. However, under certain conditions, it also provides arginine for protein synthesis, and anaplerosis occurs by the synthesis of ornithine from glutamate. 

Ornithine decarboxylase (ODC) and arginine decarboxylase (ADC) are the first enzymes involved in the formation of tropane alkaloids (TPAs) snch as atropine and cocaine (Fig. 3). Decarboxylation of ornithine yields pntrescine, whereas arginine is converted to agmatine, which is metabolized to putrescine via a second rente. ADC is assnmed to play the primary role in TPA synthesis [18]. 

Carbon Metabolism of Amino Acids. Nine of the 18 common amino acids are related directly or indirectly to the dicarboxylic acids of the citrate cycle. Proline, histidine, and arginine (or ornithine) produce glutamate and thence a-ketoglu-tarate (on the chart, below the citrate cycle). The aromatic amino acids are broken down to fumarate, which is also formed from aspartate in the urea cycle. Lastly, alanine should be included, since it can enter the citrate cycle via pyruvate and acetyl-CoA. The fact that the carbon chains of amino acids enter the citrate cycle is important both for their complete degradation and for their conversion to carbohydrates (as mentioned already, cf. Chapt. XV-10). The synthesis of amino acids cannot always proceed by a reversal of the breakdown many of them are essential components of the diet (cf. Chapt. XXII-2). 

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