Phenylketonuria-Little Molecules Have Big Effects

Phenylketonuria-Little Molecules Have Big Effects

Mutations leading to deficiencies in enzymes are usually referred to as “inborn errors of metabolism,” because they involve defects in the DNA of the affected individual. Errors in enzymes that catalyze reactions of amino acids frequently have disastrous consequences, many of them leading to severe forms of mental retardation. Phenylketonuria (PKU) is a well-known example. In this condition, phenylalanine, phenylpyruvate, phenyllactate, and phenylacetate all accumulate in the blood and urine. Available evidence suggests that phenylpyruvate, which is a phenylketone, causes mental retardation by interfering with the conversion of pyruvate to acetyl-CoA (an important intermediate in many biochemical reactions) in the brain. It is also likely that the accumulation of these products in the brain cells results in an osmotic imbalance in which water flows into the brain cells. These cells expand in size until they crush each other in the developing brain. In either case, the brain is not able to develop normally.

Fortunately, PKU can be easily detected in newborns, and all 50 states and the District of Columbia mandate that such a test be performed because it is cheaper to treat the disease with a modified diet than to cope with the costs of a mentally retarded individual who is usually institutionalized for life. The dietary changes are relatively simple. Phenylalanine must be limited to the amount needed for protein synthesis, and tyrosine must now be supplemented, because phenylalanine is no longer a source. You may have noticed that foods containing aspartame carry a warning about the phenylalanine portion of that artificial sweet-ener. A substitute for aspartame, which carries the trade name Alatame, contains alanine rather than phenylalanine. It has been introduced to retain the benefits of aspartame without the dan-gers associated with phenylalanine.