The significance and mechanism of an increased serum phenylalanine-tyrosine ratio during infection.

Infections or inflammatory states often cause significant increases in serum phenylalanine and the phenylalanine-tyrosine ratio. More than 95% of samples obtained during inflammatory diseases in man showed phenylalanine-tyrosine ratio increases greater than the maximum normal values. An increase in this ratio also occurred in monkeys with induced Rocky Mountain spotted fever, viral encephalitis, yellow fever, or pneumococcal and Salmonella infections, as well as in rats with pneumococcal and Salmonella infections, as well as in rats with pneumococcal, Salmonella or tularemia infections. A similar ratio increase occurred in rats inoculated with unpurified mediator substances (released by activated leukocytes) that appear to initiate many of the secondary metabolic phenomena associated with infection and/or inflammation. To identify responsible mechanisms, rats were given lethal doses of Streptococcus pneumoniae; serum phenylalanine and phenylalanine-tyrosine ratios increased significantly. Hepatic phenylalanine hydroxylase activities were slightly decreased when compared to noninfected controls. Infected and noninfected rats showed comparable oxidation rates for 14C-phenylalanine given with an oral phenylalanine load, as a pulse-oral dose, or as an intraperitoneal injection. After 8 hr, both infected and control rats had similar amounts of radioactivity in total body protein, but tissue distributions were markedly altered during pneumococcal sepsis. Serum proteins of infected rats contained almost twice as much total radioactivity as that found in controls, while the amount of labeled phenylalanine in skeletal muscle protein was significantly reduced in the infected group. Isolated muscles from infected rats released more phenylalanine and less tyrosine than control muscles. Infection-related increases in serum phenlalanine could not be explained by decreased hydroxylation or oxidation. Rather, the data were consistent with an increased flux of phenylalanine into serum, most likely as the result of increased skeletal muscle catabolism. Elevations in the serum phenylalanine-tyrosine ratio have potential value for estimating the presence of an inflammatory fisease and the catabolic state of a patient.