5 Arginine , Citrulline , and Ornithine

Metabolism as well as function of the three amino acids, L-arginine, L-citrulline, and Lornithine, are closely intertwined and related to the homeostasis of nitric oxide at the tissue and cellular levels. For the three compounds data on neural tissue and CSF levels are summarized and localization in brain mainly derived from immunohistochemical experiments is reported. A complex pattern of differential cellular localization, subcellular compartmentation and expression of isoforms holds for the enzymes involved in the synthesis and degradation of all three amino acids in the nervous system. Trafficking of arginine or citrulline between particular neural cell populations is likely, and transport mechanisms and proteins involved are discussed. Up-regulation of arginine synthesis and transport by proinflammatory agents satisfies the need of induced nitric oxide synthase for its substrate arginine especially in glial cells. Nitric oxide-related pathologies in the nervous system cannot be separated from the metabolic network established for the three amino acids; however, pharmacological intervention has to take into account the manyfold functions of arginine, citrulline, and ornithine in undisturbed neural cell physiology. List of abbreviations: AD, Alzheimer’s disease; ADC, Arginine decarboxylase; ADMA, Asymmetric N, N-dimethylarginine; AGAT, Arginine: glycine amidinotransferase; ASL, Argininosuccinate lyase; ASS, Argininosuccinate synthetase; CAT, Cationic amino acid transporter; CPS, Carbamoylphosphate synthetase; DDAH, N, N-dimethyl-L-arginine dimethylaminohydrolase; IFN-γ, Interferon-γ; LPS, Lipopolysaccharide; NMMA, N-monomethylarginine; NOS, Nitric oxide synthase; OAT, Ornithine aminotransferase; ODC, Ornithine decarboxylase; OTC, Ornithine carbamoyltransferase; PAD, Peptidylarginine deiminase