Brain transaminases

The initial enthusiasm for tacrine and velnacrine, which are the anticholinesterases most studied clinically, has been tempered by the fact that not all patients respond. Most show the peripheral parasympathomimetic effects of cholinesterase inhibition, e.g. dyspepsia and diarrhoea, as well as nausea and vomiting, and about half of the patients develop hepatotoxicity with elevated levels of plasma alanine transaminase. While some peripheral effects can be attenuated with antimuscarinics that do not enter the brain, these add further side-effects and the drop-out rate from such trials is high (<75%) in most long-term studies. Donepezil appears to show less hepatotoxicity but its long-term value remains to be determined. 

Schousboe, A., Wu, J. Y., and Roberts, E. (1973) Purification and characterization of the 4-aminobutyrate-2,ketoglutarate transaminase from mouse brain. Biochemistry 12,2868-2873. 

Valproic acid and its salts are a new group of antiepileptic drugs that differs from the known drugs both structurally and in terms of its mechanism of action. It is believed that it acts on the metabolism of the GABA system. Valproic acid has been shown to elevate the level of GABA in the brain by means of competitive inhibition of GABA transaminase and the dehydrogenase of succinic semialdehyde. 

Transaminases participate in metabolism of most of the amino acids, over 60 different enzymes have been identified.142163 Best studied are the aspartate aminotransferases, a pair of cytosolic and mitochondrial isoenzymes which can be isolated readily from animal hearts. Their presence in heart muscle and brain in high concentration is thought to be a result of their functioning in the malate-aspartate shuttle... 

Other effects that have been reported after accidental exposure to chlorine, include palpable and painful liver (Tatarelli 1946, as cited in WHO 1982) anxiety, phobias, or hysteria (Chasis et al. 1947 Segaloff 1961, as cited in WHO 1982) electrocardiographic abnormalities (Leube and Kreiter 1971, as cited in WHO 1982) leukocytosis and elevated glutamate-pyruvate-transaminase (Leube and Kreiter 1971, as cited in WHO 1982) and brain hemorrhages (Baader 1952, as cited in NIOSH 1976). 

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