In PKU, why are there high levels of phenylpyruvate in the plasma and urine?
=> The lack of PAH activity leads to an accumulation of phenylalanine. As the concentration of this amino acid rises, side reactions with the phenylalanine generate byproducts. These are normally are present only in vanishingly small concentrations, but under these conditions, their concentrations become appreciable. One of the side reactions is the transamination reaction of phenylalanine with alpha-ketoglutarate, which generates glutamate and (more importantly) phenylpyruvate. The reaction is the analog of the transamination of alanine to pyruvate. This leads to higher-than-normal concentrations of phenylpyruvate in the bloodstream, and then in the urine.
