Glutamate synthase reaction mechanism

The only multisite Ping-Pong mechanism known in 1970 was that of transcarboxylase (methylmalonyl-CoA carboxyltransferase) (33), but a number have been identified since then, including not only reactions in which biotin, lipoic acid, and 4-phosphopantetheine are carriers between active sites, but also reactions where oxidation and reduction of a group on the enzyme occur at different sites [e.g., glutamate synthase (34)]. 

Behavioral disorders such as anorexia, sleep disturbances, and pain insensitivity associated with hyperammonemia have been attributed to increased tryptophan transport across the blood-brain barrier and the accumulation of its metabolites. Two of the tryptophan-derived metabolites are serotonin and quinolinic acid (discussed later). The latter is an excitotoxin at the N-methyl-D-aspartate (NMDA) glutamate receptors. Thus, the mechanism of the ammonium-induced neurological abnormalities is multifactorial. Normally only small amounts of NH3 (i.e., NH4 ) are present in plasma, since NH3 is rapidly removed by reactions in tissues of glutamate dehydrogenase, glutamine synthase, and urea formation. 

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