Inhibition of the mitochondrial respiratory chain by alanine in rat cerebral cortex

Alanine is a nutritionally nonessential amino acid synthesized by transamination of pyruvate originated from glucose. Alanine is the principal gluconeogenic amino acid because it can originate pyruvate and glucose through the inverse pathway. Considering that it has been suggested that alanine could be used as a dietary supplement in combination with growth hormone in the treatment of undernourished children affected by some inherited metabolic diseases to induce anabolism, the principal objective of the present work was to measure the activities of the mitochondrial respiratory chain complexes and succinate dehydrogenase in brain cortex of Wistar rats subjected to chronic alanine administration from the 6th to the 21st day of life. We also investigated the in vitro effect of alanine on the activities of mitochondrial respiratory chain complexes and succinate dehydrogenase in the same brain structure of 22-day-old rats. The results showed a reduction of Complex I + III and succinate dehydrogenase activities in brain cortex of rats subjected to alanine administration. We also verified that alanine inhibited the in vitro activity of Complexes I + III by competition with NADH. These results indicate that more investigation would be necessary before considering alanine supplementation as a valid adjuvant therapy to sick children with these disorders.