The inhibitory action of L-dihydroxyphenylalanine (L-dopa) in the presence of a monoamine oxidase inhibitor on protein synthesis in vivo and the partial amelioration of this by methionine supplementation.

Male Wistar rats of various age groups were injected daily over a period of 3 weeks with iproniazid (10 micrograms/g body wt.) and L-dihydroxyphenylalanine (L-dopa; 0.1 mg/g body wt.). On the final day 1 h before the termination of the experiment the animals were injected with L-[14C]valine (0.1 microCi/g body wt.). The specific radioactivity of the valine in the proteins of the subcellular fractions of the tissues examined, relative to the time-integrated mean specific radioactivity of this amino acid in the acid-soluble pools of these tissues, was used to assess protein synthesis. The L-dopa/monoamine oxidase-inhibitor treatment was associated with 30--40% inhibition of protein synthesis. Supplementation of the dietary methionine intake by injection of this amino acid markedly diminished the inhibitory action of the L-dopa/monoamine oxidase-inhibitor treatment on protein synthesis in all fractions examined.

Turnover of myelin and other structural proteins in the developing rat brain.

1. Protein metabolism of myelin and other subcellular components from developing rat brain was studied for periods from 5h to 210 days after intraperitoneal injection of [(3)H]lysine and [(14)C]glucose. 2. Half-lives for total brain proteins (t(0.5)) were 27 days after [(3)H]lysine and 4 days after [(14)C]glucose injection. 3. Factors accounting for the difference in the turnover rates obtained with different precursors, and the problem of reutilization of the label were investigated. 4. The catabolism of purified myelin proteins was studied and the half-lives of individual myelin proteins were calculated. 5. Myelin basic proteins turned over at two different rates. Half-life of the fast component of myelin basic proteins was 19-22 days and the slow component exhibited a high degree of metabolic stability. 6. Proteolipid protein underwent slow turnover. High-molecular-weight Wolfgram (1966) proteins underwent (relatively) fast metabolism (t(0.5) of 17-22 days).

The identity of a myelin-like fraction isolated from developing brain.

1. A myelin-like membrane fraction was isolated from developing rat brain by a new method. 2. The chemical composition and morphology of the fraction are described. 3. The myelin-like fraction is similar to myelin in characteristic enzyme activity but differs in the absence of basic protein and cerebrosides. No similarity to other subcellular fractions was observed. 4. It is suggested that the myelin-like fraction is a stage in the formation of compact myelin from glial plasma membrane. 5. ;Early' myelin consists of the myelin-like and compact myelin fractions from developing brain.

Effect of phenylalanine on protein synthesis in the developing rat brain.

1. Inhibition of the rate of incorporation of [(35)S]methionine into protein by phenylalanine was more effective in 18-day-old than in 8-day-old or adult rat brain. 2. Among the subcellular fractions incorporation of [(35)S]methionine into myelin proteins was most inhibited in 18-day-old rat brain. 3. Transport of [(35)S]methionine and [(14)C]leucine into the brain acid-soluble pool was significantly decreased in 18-day-old rats by phenylalanine (2mg/g body wt.). The decrease of the two amino acids in the acid-soluble pool equalled the inhibition of their rate of incorporation into the protein. 4. Under identical conditions, entry of [(14)C]glycine into the brain acid-soluble pool and incorporation into protein and uptake of [(14)C]acetate into lipid was not affected by phenylalanine. 5. It is proposed that decreased myelin synthesis seen in hyperphenylalaninaemia or phenylketonuria may be due to alteration of the free amino acid pool in the brain during the vulnerable period of brain development. Amyelination may be one of many causes of mental retardation seen in phenylketonuria.