Michael J. Carver

INFLUENCE OF PHENYLALANINE ADMINISTRATION ON THE FREE AMINO ACIDS OF BRAIN AND LIVER IN THE RAT.

RECENT studies have indicated that L-phenylalanine inhibits antibody response to diphtheria toxoid in rats and rabbits (RYAN and CARVER, 1964). It was suggested, as an explanation for the inhibition, that excess phenylalanine caused a disturbance in the free amino acids of the animals with a resultant decrease in antibody (protein) synthesis. It is also conceivable that chronic alterations in the amino acids of the central nervous system induced by phenylalanine could also give rise to changes in protein synthesis. Since an excess or deficiency of an amino acid might exert an effect on the distribution of other amino acids, a quantitative study of the amino acids in rat brain and liver was conducted to assess the influence of phenylalanine on the concentration of the other amino acids.

CHARACTERIZATION OF ACIDIC PROTEINS IN CELL ACRYLAMIDE GEL ELECTROPHORESIS NUCLEI FROM RAT BRAIN BY HIGH‐RESOLUTION1

Abstract— Acidic proteins from cell nuclei of rat brain were evaluated by gel electrophoresis. By the use of a gel containing a high ratio of bis‐acrylamide to acrylamide, 31 bands were demonstrated for this protein fraction. Gels without the high concentration of copolymer lacked the resolving power to separate these proteins. Because the number of bands present in the acidic protein fraction is greater than the number of histones present in cell nuclei, the suggestion that the acidic proteins play a role in genetic regulation seems reasonable.

Immediate and Prolonged Effects of Hydrocortisone on the Free Amino Acids of Rat Skeletal Muscle.

Summary 1. Twenty-four hours after injection hydrocortisone was found to increase the free amino acids of the plasma and muscle of the rat. These acids are decreased after 10 days of treatment with hydrocortisone. 2. Hydrocortisone produced increases in aspartic acid in the muscles of rats treated for 24 hours and for 10 days. This increase after 10 days occurred in spite of a 40% decrease in aspartic acid concentration in the plasma. 3. The muscle/plasma ratios of glycine, glutamine and glycine were found to decrease at 24 hours and at 10 days. This suggests that hydrocortisone inhibits the transport of these amino acids.

Ion-exchange chromatography of urinary amino acids: I. normal children

Abstract An investigation of the quantitative urinary amino acid patterns from twelve children above three years of age has been presented using ion-exchange chromatography. The results indicated that the patterns obtained resembled those previously reported for adults.

EXPERIMENTAL MATERNAL HYPERPHENYLALANINEMTA: DISAGGREGATION OF FETAL BRAIN RIBOSOMES

Disaggregation of polyribosomal structures has been demonstrated in fetal rat brains following treatment of the maternal animal with para‐chloro‐d,l‐phenylalanine (used primarily to inhibit maternal phenylalanine hydroxylase, EC 1.14.3.1) and with phenylalanine (used to raise the level of circulating phenylalanine in maternal and fetal plasma). Since highly disaggregated polyribosomal systems cannot support normal levels of protein synthesis in vitro, it has been postulated that the composition of the free amino acid pool(s) plays a regulatory role in protein synthesis through the intermediary effect of polyribosomal aggregation‐disaggregation. We believe that a possibly prolonged period of disaggregation of neuronal polyribosomes might disrupt neuronal protein synthesis sufficiently in utero to produce the mental insufficiency observed in the offspring of untreated maternal phenylketonurics.

Differential effects of phenothiazines on hexose phosphate dehydrogenases

Abstract Glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase from beef adrenal were inhibited by a variety of substituted phenothiazines. With similar enzymes isolated from rat brain tissue only glucose-6-phosphate dehydrogenase was affected. Kinetic studies with the brain enzyme gave no evidence of competitive inhibition. Results with imipramine, including kinetic studies, were in most instances similar to those obtained with the phenothiazines.

Protein Metabolism in the Developing Brain: Influence of Birth and Gestational Age

Incorporation of carbon-14-labeled phenylalanine into brain protein of newborn pigs falls sharply within 24 hours after birth. This decrease is related to the time of birth rather than the gestational age of the piglets, although the latter is also associated with a gradual decrease in brain protein synthesis.

Daily variations in phenylalanine hydroxylase activity in male and female guinea pigs

Abstract Phenylalanine hydroxylase of guinea pig liver exhibited circadian rhythmicity in male animals, but not in female animals. Female guinea pigs showed variations in plasma phenylalanine and tyrosine which were similar to those observed over the same period for male animals. Reversal of the lighting cycle resulted in a marked change in cycles of plasma phenylalanine and tyrosine, but had little effect on the rhythm of hepatic phenylalanine hydroxylase activity. Peak phenylalanine hydroxylase activity in guinea pigs followed a few hours behind the peak of the rhythm of the phenylalanine/tyrosine ratio in plasma.

Inhibition of Antibody Synthesis by L·Phenylalanine

Antibody synthesis in response to the injection of diphtheria toxoid into rabbits and rats was used to study the effects of an excess of the amino acid L-phenylalanine on protein synthesis. Injections of phenylalanine produced a marked inhibition of antibody synthesis in both the rat and the rabbit. The dosage of phenylalanine used caused an increase over the normal concentration of phenylalanine in the plasma and spleen of rats, but did not cause a loss of weight or serum protein changes in the treated animals.

The effect of tranquilizing agents and related compounds on the succinoxidase system.

Abstract The effect of 13 tranquilizing agents or their pharmacologically inactive analogs on the succinoxidase system was determined. The phenothiazine group of drugs inhibited the succinoxidase system most strongly and was followed closely in this property by reserpine, the derivatives of phenyl carbinol being the least active. Quiactin was relatively inactive. In all cases, cytochrome oxidase was more sensitive and succinic dehydrogenase less sensitive to inhibition than the complete succinoxidase system. Brain succinoxidase was less sensitive to inhibition than liver succinoxidase. It is concluded that inhibition of succinoxidase is not related to the mechanism of action of the tranquilizers.