Transaminase inhibitors

The high toxicity of AOA is due to its very high efficiency as a transaminase inhibitor (K =0.45 pM) as compared to its efficacy as a PAL inhibitor (K. = 120 pM) (48), making it impossible to effectively inhibit PAL iti vivo without also greatly inhibiting amino acid metabolism. Other pyridoxyl phosphate-requiring enzymes, such as ACC synthase (an enzyme involved in ethylene production) (49), are also more sensitive to AOA than to AOPP. 

Valproic acid (= 2-Propylpentanoic acid 2-Propylvaleric acid)] (carboxylic acid) Synthetic GABA transaminase inhibitor (cf. 4-Hydroxybenzaldehyde) [anticonvulsant, antiepileptic]... 

Wilhamson s experiments were carried out in the presence of transaminase inhibitors, and his kinetic parameters are inconsistent with rates of aspartate transport measured under more physiological conditions, using isolated mitochondria [134,140,142]. Although consistent with fluxes and metabolite levels measured in hepatocytes under a limited range of conditions [102,139], examination of a broader range of conditions reveals order of magnitude discrepancies between predicted and observed rates [143]. 

Palfreyman M G, Schechter P J, Buckett W R, Tell G P, and Koch Weser J. (1981) The pharmacology of GABA-transaminase inhibitors, Biochem. Pharmacol 30, 817-824... 

When we were developing an assay for the estimation of PAL activity in intact cells,we employed a-aminooxy-acetate (AOA) as a transaminase inhibitor. When it became clear that AOA was a weak inhibitor of buckwheat PAL (K = 120 we rationalized that the aminooxy analog of... 

Synthesis of Glycosylated Natural Products.-Sarmentosin 18 which is a potent glutamic-pyruvic transaminase inhibitor has been made from an acetylated glycosyl glycerol derivative. ... 

---