Ornithine, biosynthesis from arginine

The A-methyl-A -pyrrolinium cation is the last common intermediate in both tropane alkaloid and nicotine biosynthesis (Scheme 3). A-Methyl-A -pyrrolinium cation formation begins with the decarboxylation of ornithine and arginine by ornithine decarboxylase (ODC) and arginine decarboxylase (ADQ, respectively. Putresdne is formed directly from ornithine by ODC, whereas agmatine and A-carbamoylputresdne serve as intermediates when putrescine is formed via ADC. An ODC cDNA isolated from Datura stramonium showed similarity to ADCs and other ODCs 127). ADC cDNAs have been isolated from oat and tomato 128,129). Arginine appears to supply most of the putrescine for alkaloid biosynthesis (l30). 

Muscle activity involves processes such as aerobic and anaerobic glycolysis and is therefore accompanied by an increased pyruvate production. Consequently, the pyruvate transamination product alanine will be increased after exercise. Heavy exercise may be associated with an increased need of creatine biosynthesis from arginine. Ornithine is a by-product of this pathway and may be increased under these conditions. 

FIGURE 3-8 Uncommon amino acids, (a) Some uncommon amino acids found in proteins. All are derived from common amino acids. Extra functional groups added by modification reactions are shown in red. Desmosine is formed from four Lys residues (the four carbon backbones are shaded in yellow). Note the use of either numbers or Creek letters to identify the carbon atoms in these structures, (b) Ornithine and citrulline, which are not found in proteins, are intermediates in the biosynthesis of arginine and in the urea cycle. 

Secondary metabolites can accumulate in the same cell and tissue in which they are formed, but intermediates and end-products can also be transported to other locations for further elaboration or accumulation. For example, TAs and nicotine are typically produced near the root apex, but mostly accumulate within leaf cell vacuoles. Even TA biosynthesis itself involves intercellular transport of several pathway intermediates (Fig.7.9A). P-Glucuronidase (GUS) localization in A. belladonna roots transformed with a PMT promoter-GUS fusion showed that PMT expression is restricted to the pericycle.144 Immunolocalization and in situ RNA hybridization also demonstrated the pericycle-specific expression of H6H.145,146 In contrast, TR-I was immunolocalized to the endodermis and outer root cortex, whereas TR-II was found in the pericycle, endodermis, and outer cortex.85 The localization of TR-I to a different cell type than PMT and H6H implies that an intermediate between PMT and TR-I moves from the pericycle to the endodermis (Fig.7.9A). Similarly, an intermediate between TR-I and H6H must move back to the pericycle. The occurrence of PMT in the pericycle provides the enzyme with efficient access to putrescine, ornithine, and arginine unloaded from the phloem. In the same way, scopolamine produced in the pericycle can be readily translocated to the leaves via the adjacent xylem. 

Tropane alkaloid biosynthesis has been studied at the biochemical level, and several enzymes from the biosynthetic pathway have been isolated and cloned, although the pathway has not been elncidated completely at the genetic level (Fig. 3b) (138). L-arginine is converted to the nonproteogenic amino acid L-omithine by the nrease enzyme arginase. Ornithine decarboxylase then decarboxylates ornithine to yield the diamine pntrescine. In Hyoscyamus, Duboisia, and Atropa, putrescine serves as the common precnrsor for the tropane alkaloids. 

The nonessential amino acids are synthesized by quite simple reactions, whereas the pathways for the formation of the essential amino acids are quite complex. For example, the nonessential amino acids alanine and aspartate are synthesized in a single step from pyruvate and oxaloacetate, respectively. In contrast, the pathways for the essential amino acids require from 5 to 16 steps (Figure 24.8). The sole exception to this pattern is arginine, inasmuch as the synthesis of this nonessential amino acid de novo requires 10 steps. Typically, though, it is made in only 3 steps from ornithine as part of the urea cycle. Tyrosine, classified as a nonessential amino acid because it can be synthesized in 1 step from phenylalanine, requires 10 steps to be synthesized from scratch and is essential if phenylalanine is not abundant. We begin with the biosynthesis of nonessential amino acids. 

The first key step in the biosynthesis of tropane alkaloids is the formation of the intermediate putrescine. Polyamines and, therefore putrescine, are found in plant cells and are implicated in growth, root, fruit and flower development, and in different stress phenomena. It is well known that plants synthesize polyamines from ornithine and arginine, unlike other eukaryotes like mammals, which only synthesize polyamines from ornithine. In plants putrescine is synthesized directly from ornithine, a reaction catalysed by ornithine decarboxylase (ODC, EC 4.1.1.17) and indirectly from arginine via agmatine catalysed by arginine decarboxylase (ADC, EC 4.1.1.19), Fig. (1). In Arabidopsis, it is known that the adc gene is required for the production of polyamines that are essential for normal seed development [103]. 

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... 

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