Citrulline, synthesis transport

Citrulline is transported to the cytoplasm where it condenses with aspartate, the donor of the second amino group of urea. This synthesis of argininosuccinate, catalyzed by argininosuccinate synthetase, is driven by the cleavage of ATP into AMP and pyrophosphate and by the subsequent hydrolysis of pyrophosphate. 

According to Halestrap [98] activation of mitochondrial electron transport not only increases the proton-motive force but also the intramitochondrial ATP concentration which is important for intramitochondrial ATP utilising reactions like pyruvate carboxylation and citrulline synthesis, processes known to be activated by glucagon. Siess et al. [35], however, showed that in hepatocytes glucagon not only increased mitochondrial ATP, but also the sum of ATP, ADP and AMP at the expense of the cytosolic pool of adenine nucleotides, a phenomenon to which no attention has been paid in the literature. Exchange between ADP and ATP cannot increase the mitochondrial adenine nucleotide pool. Possibly net influx of adenine nucleotides can occur via exchange between ADP and mitochondrial phosphoenol-pyruvate (see [4] for literature). 

Figure 1. Contribution of different pathways to the ornithine usedfor citrulline synthesis. De novo synthesis of ornithine Proline is oxidised by action of proline oxidase (1) to generate pyrrolidine-5-car boxy late (P5C). P5C interconverts spontaneously with glutamate semialdehyde (GSA). Glutamine is deamidated by action of glutaminase (2) and the resulting glutamate is converted into GSA by pyrrolidine-5-carboxylate synthase (3). GSA is used by ornithine aminotransferase (OAT 4) to generate ornithine. Note that OAT is usedfor both synthesis and disposal of ornithine. Preformed ornithine ornithine is generatedfrom the hydrolysis of arginine by arginase (5), or can be transported from plasma. Ornithine is used for citrulline synthesis by action of ornithine transcarbamylase (OTC 6).

Substrate sources Increased transmembrane transport No citrulline recycling Increased transmembrane transport Increased endogenous synthesis from citrulline... 

Transport of ornithine and citrulline, important for urea synthesis in liver, has been a controversial issue too [6]. In Fig. 1 transport of ornithine and citrulline is depicted as two separate pathways, but this has not yet been settled. It is also possible that ornithine exchanges with citrulline. 

Ureides are a class of cyclic or acyclic nitrogenous organic compounds derived from or structurally related to urea. Representatives of this class which have been found in plants include allantoin, allantoic acid, citrulline, uric acid, hypoxanthine, xanthine, caffeine, hydroxycitruUine, and albizziine. The structures of allantoin (ALN), allantoic acid (ALA), and citrulline (CIT), ureides which occur throughout the plant kingdom, are presented in Fig. 1. These ureido compounds play an essential role in the assimilation, metabolism, transport, and storage of nitrogen in plants. In this chapter, attention will be focused on the occurrence, function, synthesis, and metabolism of these key metabolites. 

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