Effect of excess phenylalanine and of other amino acids on brain development in the infant rat.

Abstract

Extract: The effects of excess phenylalanine and of a number of other amino acids on brain weight, total brain lipid, and formation of the myelin lipid cerebroside sulfate (sulfatide) have been studied in the newborn rat. Brain weight, amount of brain lipids, and the formation in vivo of sulfatide were reduced as a result of injections of phenylalanine or of certain other amino acids. Total brain cholisterol, cerebroside, and sulfatide were all significantly reduced in phenylalanine-injected animals, although sulfatide was the only lipid that was reduced per gram wet weight of brain. The in vitro activity of the brain enzyme, galactolipid sulfotransferase, which catalyzes the formation of sulfatide from cerebroside and adenosine 3′-phosphate 5′-phosphosulfate (PAPS), was significantly reduced only when exogenous PAPS was not added to the assay medium. This finding suggests that in the brains of animals injected with phenylalanine there was impairement in the formation of PAPS from ATP and sulfate. In both cerebrums and cerebellums of animals injected with phenylalanine for the first 18 days of life, the amount of brain DNA and protein was reduced. Speculation: Increased ambient tissue levels of a number of amino acids, including phenylalanine, may interfere with normal development of the infant rat brain.