Aspartic acid physiological roles

Glutamatergic AMPA (a-amino-3-hydroxy-5-methyM-isoxazolpropionic acid) and NMDA (N-methyl-D-aspartate) receptors are also found together with glutamatergic inputs from the LH (Yang Hatton, 1997), although the physiological role of this excitation remains unclear (Haas Panula, 2003). 

Aspartic proteases have also been proposed as the ECE of primary interest. Enzymes of this type have been isolated from a range of tissues and have been shown to cleave big ET-1 to ET-1. The case has been proposed for pepsin, cathepsin D and cathepsin E being the important enzyme, the latter being very attractive since the human enzyme has been shown to give only ET-1 and the C-terminal fragment (22-38) as big ET-1 breakdown products [62]. However, their physiological roles continue to be questioned as they require an acidic environment for activity. Inhibitors of the aspartic protease from rat lung tissue have been reported [63] but there is no information on inhibitors of the other aspartic enzymes. 

D-aspartic acid, unlike L-form, has a physiological role in the nervous system and to some extent the reproductive system (D Aniello, 2007 Scanlan et al., 2010). D-aspartic acid plays an important role in the brain and testes, where it initiates the release of growth hormones and is also involved in the regulation of testosterone (D Aniello, 2007 Huanga et al., 2009 Scanlan et al., 2010). It has also been reported to be present in a wide variety of species, both in vertebrates and invertebrates (D Aniello et al., 1995a,b). 

The N-methyl-D-aspartate (NMDA) receptor is a ligand-gated ion channel that is present throughout the mammalian CNS and is activated by the excitatory amino acid, glutamate. This receptor plays a fundamental role in a number of physiological processes and may be an avenue for the treatment of such disease states as stroke, Parkinson s disease and neuropathic pain. Agents that block the NMDA channel have been shown to alleviate pain in human clinical trials, however the low therapeutic index over side effects such as loss of motor coordination make such compounds unattractive for chronic therapy. 

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