Possible Interaction: Alanine and Cycloserine

“2 In Na+‐free media with the … held at pH 6.0, D‐cycloserine (20 mM) is an effective … net transepithelial transport (Jnet) of L‐alanine (100 μm) and its accumulation (across the apical membrane) in a similar … amino acid substrates (L‐alanine, β‐alanine, L‐proline and glycine).”

“… L‐alanine … D‐cycloserine were dose‐dependent, maximal inhibition being achieved by 5–10 mM. 3 Both D‐cycloserine and known substrates for H+/amino acid symport …‐2 epitheha, mounted in Ussing chambers, were exposed to apical substrate in Na+‐free media, with apical pH held at 6.0.”

“We then experimentally show that two competitive inhibitors of ALAT, l-cycloserine and β-chloro-l-alanine, inhibit l-alanine production and impair d-glucose uptake of LLC1 Lewis lung carcinoma cells.”

“The aminotransferase inhibitors L-cycloserine and carboxymethoxylamine inhibited growth and selectively inhibited the production of alanine.”

“ L-cycloserine , an inhibitor of alanine aminotransferase, significantly (P less than .05) reduced alanine following hepatectomy.”

“At a dose (30 mg/kg) which elevated the level of GABA almost 4-fold, L-cycloserine moderately increased the content of alanine and slightly reduced that of aspartate, glutamate and glycine in the brain.”

“By comparison with preincubation with inhibitors, simultaneous addition of substrates alanine ; lactate plus lysine) and inhibitors ( cycloserine ; aminomethoxybutenoic acid) resulted in smaller decreases in aminotransferase activities and in metabolic rates.”

“Administration of l-cycloserine , an inhibitor of glutamate-alanine aminotransferase, completely prevented the increase in [ alanine ] after the ammonia load; in this case the absolute increase in [aspartate] was higher.”

“Injection of l-cycloserine 60min before the rats were killed increased the concentration of alanine in the liver fourfold and decreased the concentration of the other metabolites measured, except that of pyruvate.”

“Of a number of other potential reversing agents, only dl-alanyl-dl-alanine reversed the effect of d-cycloserine on mouse pneumonitis agent.”

“ DCS was found to competitively inhibit d‐Ala binding at both MtDdl d‐Ala sites with equal affinity (Ki,DCS1 = 14 μm, Ki,DCS2 = 25 μm); however, each enzyme active site can only accommodate a single DCS molecule at a given time.”