V R Young

Plasma arginine kinetics in adult man: Response to an arginine-free diet

To explore the response of whole-body arginine metabolism to a change in arginine intake, plasma arginine kinetics were investigated in eight healthy adult men who received an L-amino acid diet supplying an Arg-rich or Arg-free intake for 6 days before undergoing a tracer study on day 7. The tracer protocol lasted for 8 hours. For the first 3 hours subjects remained in the postabsorptive (fasted) state, and during the following 5 hours they consumed small meals at 30-minute intervals. Primed continuous intravenous infusions of L-[guanidino-13C]arginine, L-[5,5,5-2H3]leucine, and [15N2]urea were administered to estimate plasma amino acid fluxes and the rate of urea production. For the fasted and fed states, plasma arginine fluxes (mumol.kg-1.h-1, mean +/- SD) were 69 +/- 8 and 87 +/- 12 (P < .01), respectively, for the Arg-rich diet and 63 +/- 14 and 51 +/- 7 (P < .01, from Arg-rich) for the Arg-free diet. Compared with the Arg-rich results, fed-state plasma arginine and ornithine concentrations were decreased (P < .01) and citrulline concentration was increased (P < .01) during the Arg-free diet period. Leucine fluxes and rates of urea production did not differ between the diet groups. The lower fed-state arginine flux in subjects receiving the Arg-free compared with the Arg-rich diet appears to be entirely due to the decreased rate of entry of arginine from the intestine in the former group.(ABSTRACT TRUNCATED AT 250 WORDS)

Phenylalanine conversion to tyrosine: Comparative determination with l-[ring-2H5]phenylalanine and l-[1-13C]phenylalanine as tracers in man

The in vivo rate of conversion of phenylalanine to tyrosine (PheOH) can be estimated using combinations of stable isotope-labeled phenylalanine and tyrosine. We have compared in four healthy adult men the rates of phenylalanine conversion to tyrosine based on the following pairs of primed, continuous tracer infusions administered simultaneously: (1) L-[ring-2H5]phenylalanine and 2H2-tyrosine with a 2H4-tyrosine prime, and (2) L-[1-13C]phenylalanine and 2H2-tyrosine with a 1-13C-tyrosine prime. Phenylalanine oxidation was determined from measurement of 13CO2 excretion in expired air. Tracers were given for 8 hours, with subjects being in the postabsorptive state during the first 3 hours and in the fed state during the remaining 5 hours. Mean (+/- SD) rates (mumol.kg-1.h-1) of phenylalanine conversion to tyrosine for fasted and fed states, respectively, were 5.1 +/- 2.9 and 6.8 +/- 3.4 with 2H5-phenylalanine and significantly higher (P < .05) at 11.1 +/- 5.6 and 12.7 +/- 7.7 with 13C-phenylalanine as tracer. Phenylalanine oxidation was 9.9 +/- 2.0 and 13.5 +/- 2.6, respectively, for fasted and fed states, and these mean values did not differ (P > .1) from the rate of phenylalanine conversion to tyrosine determined using 13C-phenylalanine. These results indicate the need for caution in interpreting kinetic aspects of phenylalanine metabolism when based on isotopic data from multideuterated phenylalanine.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of corticosterone and its route of administration on muscle protein breakdown, measured in vivo by urinary excretion of Nτ-methylhistidine in rats: Response to different levels of dietary protein and energy

Abstract Adrenalectomized young male rats were given a large dose of corticosterone ( 10 mg 100 gm body weight ) either by subcutaneous or intraperitoneal injection. Subcutaneous injection caused immediate cessation of growth and an elevation in urea and in Nτ-methylhistidine (3-Mehis) output in the urine, the latter indicative of accelerated muscle protein breakdown. On the other hand, intraperitoneal administration resulted in only slight retardation of growth and no change in 3-Mehis output. Since the plasma level of corticosterone was more elevated by subcutaneous than by intraperitoneal administration of the hormone, it was concluded that direct passage of the intraperitoneal dose through the liver inactivated more of the administered hormone and thus prevented the level in the peripheral blood from rising to the critical concentration necessary to cause acceleration of muscle protein breakdown. This explains some reports in the literature of lack of action of corticosteroids on muscle protein breakdown. When corticosterone ( 10 mg 100 gm body weight ) was administered subcutaneously to young adrenalectomized rats receiving diets deficient in protein and/or energy, they lost weight at the same rate as did rats on an adequate diet. In addition, the gastrocnemius, tibialis, and extensor digitorum longus muscles lost weight and output of 3-Mehis was elevated irrespective of the diet. When a lower dose of corticosterone ( 0.8 mg 100 g body weight ) was given subcutaneously, the pattern of growth or weight loss on the different diets was not affected and the weights of the leg muscles relative to body weight remained unchanged. Output of 3-Mehis was slightly and transiently elevated for rats on the energy-deficient and protein-energy deficient diets receiving this low dose of corticosterone, but not for rats on the protein-deficient or adequate diets. Since the livers of the animals on the low energy intakes were smaller, we attribute the slight action of the lower corticosterone dose on 3-Mehis output to less efficient hepatic removal of the hormones. Thus, diet appears to modify the action of corticosteroids mainly through changes in the rate of hormone inactivation. It is concluded that dietary intake of protein and energy and corticosterone affect muscle protein turnover independently of one another.