Renal Amino Acid Reabsorption in Hyperphenylalaninemic Monkeys Infused with β-2-Thienylalanine 1

β-2-Thienylalanine (α amino-thiopheneproprionic acid), first synthesized by Barger and Easson in 1938 1 , is a potent inhibitor of phenylalanine metabolism in bacteria as shown by the bacterial-inhibition test developed by Guthrie 2 and employed in the screening of human neonates for the detection of phenylketonuria. It has been shown by Godin and Dolan 3 to affect phenylalanine metabolism in rats. When administered to mammals, β-2-thienylalanine is largely excreted by the kidney. The present study examines the effect of β-2-thienylalanine on renal excretion of phenylalanine and other amino acids in the monkey.

Methods. Four healthy, adult, male rhesus monkeys (Macaca mulatto) which weighed 6.26–8.75 kg were used. The animals were usually fed Purina Monkey Chow, fruits, and vitamins but were fasted for 8 hr before and throughout the experiment. They were lightly anesthetized with intravenous 5-allyl-5(1-methyl butyl)-2 thiobarbiturate (Surital, Parke-Davis, Co.) 30 mg/kg and an intravenous drip of 2.5% dextrose plus 0.45% sodium chloride was inserted. A collector was attached by tube to the external genitalia so that urine could be collected in a plastic bottle kept in ice. A few thymol crystals were placed in the plastic bottle to prevent bacterial growth. A control blood sample was drawn.

Each monkey was strapped into a special metabolic chair and when full consciousness was regained a control urine specimen was obtained. The animal was infused with 200 mg/kg phenylalanine 2 intravenously as a stat dose. Two monkeys (B56 and E27) were started on an infusion of phenylalanine in physiological saline at concentration of 2.0 g/100 ml and at a rate to deliver 2 g/kg/day. After 24 hr the infusion was changed to 2.0 g/100 ml phenylalanine plus 5 g/100 ml β-2-thienylalanine 3 in saline at the same rate.