n2methyl histidine: inhibitor of hepatic protein synthesis?

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F49 UTILIZATION OF PARENTERALLY ADMINISTERED AMINO ACIDS IN CHILDREN WITH CHRONIC RENAL INSUFFICIENCY. W.Uhl, U.BUrger and H.Wolf. Dept.of Ped. Univ. Giessen, FRG. Twenty children (2-16 years of age) with chronic renal insufficiency were qiven a bolus infusion (1 ml/kq bod.yweiqht) of a 10% L-amino acid solution. Blood level kinetic studies were performed after the end of the infusion. The velocity constants, half-lives, transfers and clearances, as well as the fasting concentrations of the individual amino acids were de- termined and compared with values from 20 healthy children. The fasting levels of glutamic acid, citrulline, cystine, 1-methyl-histidine, 3-methyl- histidine, hydroxiproline and B-alanine were elevated, whereas those of threonine, serine, valine, tyrosine, histidine and tryptophan were de- creased compared with controls. Calculation of the kinetic parameters de- monstrated differences between glomerular and tubular related renal insuf- ficiency. The average transfer and clearance values of patients with glo- merular related renal insufficiency lay 50-67% below those of patients with primarily tubular disease. Comparision of mean transfer values (g/kg/ h) of the essential amino acids showed: Try Phe LYS Thr Met Ile Leu Val glom. 0.2 0.6 0.6 0.5 0.2 0.3 0.6 0.8 tub. 0.4 1.4 1.3 1.2 0.4 0.6 1.2 1.6 In constrast, the halb-lives and velocity constants of both groups did not differ from normal. These results suggest a diminished protein turnover in patients with chronic renal insufficiency due to glomerular damage. F5ON*METHYL HISTIDINE: INHIBITOR OF HEPATIC PROTEIN SYNTHESIS? S.Schwarz, J. Bosch, E.Chizoni, M.Farriol, I.Bartosek. C.S.Vall d'Hebrbn. Barcelona, Spain. Inst. Rich.l-armacol.Maslo Neqri, Milano, Italy, The urinary excretion of NLMethyihistidine (His jLMeJ) has been used as an index of myofibrilar protein breakdown. The (His ( Me)) is an end product of protein degradation and it is completely excreted in human urine. In 1979 clinical studies show an inverse correlation between the plasmatic (His (LMe)) and albumin levels. have low levels of aJbumin and high On the othfr hand uremic patients levels of (His ( Me)). We can hypothe- size that the (His ( Me)) can regulate protein synthesis. In order to veri- fy this hypothesis we studied protein synthesis in perfused rat livers. We used Sprague-Dawle rats weighting 200-224 g, fed ad libitum. The livers were isolated between IO-12 AM. The perufsion medium contained Krebs-Rin- ger buffer pH 7.4 rat erytrocites l/3 (v/v), BSA 4%, glucose O.l%, piruvic acid 15 mM,41eucine 5 mM, other amino aci$s at physiologic$l rat concen- tration, U C leu 0.0625 UC/ml and (His ( Me)). The (His ( Me)) causes an important reduction of the dpm incorporated into the secreted proteins. In the control shows t5at the rate of secretion was 1.21 + 0.16 mg/g/h. The addition of (His ( Me)) at 0.05, 0.1, 0.25, 0.5, 1.0 and 2 mM causes a reduction between 40 $0 60%, and the degree of inhibition is practically indipendent of the (His Me)) conc$ntration. We can conclude that, in controlled conditions, the (His ( Me)) inhibit the hepatic protein synthesis more than the hepatic protein secretion. 50

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Page 1: N2methyl histidine: inhibitor of hepatic protein synthesis?

F49 UTILIZATION OF PARENTERALLY ADMINISTERED AMINO ACIDS IN CHILDREN WITH CHRONIC RENAL INSUFFICIENCY. W.Uhl, U.BUrger and H.Wolf. Dept.of Ped. Univ. Giessen, FRG.

Twenty children (2-16 years of age) with chronic renal insufficiency were qiven a bolus infusion (1 ml/kq bod.y weiqht) of a 10% L-amino acid solution. Blood level kinetic studies were performed after the end of the infusion. The velocity constants, half-lives, transfers and clearances, as well as the fasting concentrations of the individual amino acids were de- termined and compared with values from 20 healthy children. The fasting levels of glutamic acid, citrulline, cystine, 1-methyl-histidine, 3-methyl- histidine, hydroxiproline and B-alanine were elevated, whereas those of threonine, serine, valine, tyrosine, histidine and tryptophan were de- creased compared with controls. Calculation of the kinetic parameters de- monstrated differences between glomerular and tubular related renal insuf- ficiency. The average transfer and clearance values of patients with glo- merular related renal insufficiency lay 50-67% below those of patients with primarily tubular disease. Comparision of mean transfer values (g/kg/ h) of the essential amino acids showed:

Try Phe LYS Thr Met Ile Leu Val glom. 0.2 0.6 0.6 0.5 0.2 0.3 0.6 0.8 tub. 0.4 1.4 1.3 1.2 0.4 0.6 1.2 1.6 In constrast, the halb-lives and velocity constants of both groups did not differ from normal. These results suggest a diminished protein turnover in patients with chronic renal insufficiency due to glomerular damage.

F5ON*METHYL HISTIDINE: INHIBITOR OF HEPATIC PROTEIN SYNTHESIS? S.Schwarz, J. Bosch, E.Chizoni, M.Farriol, I.Bartosek. C.S.Vall d'Hebrbn. Barcelona, Spain. Inst. Rich.l-armacol.Maslo Neqri, Milano, Italy,

The urinary excretion of NLMethyihistidine (His jLMeJ) has been used as an index of myofibrilar protein breakdown. The (His ( Me)) is an end product of protein degradation and it is completely excreted in human urine. In 1979 clinical studies show an inverse correlation between the plasmatic (His (LMe)) and albumin levels. have low levels of aJbumin and high

On the othfr hand uremic patients levels of (His ( Me)). We can hypothe-

size that the (His ( Me)) can regulate protein synthesis. In order to veri- fy this hypothesis we studied protein synthesis in perfused rat livers. We used Sprague-Dawle rats weighting 200-224 g, fed ad libitum. The livers were isolated between IO-12 AM. The perufsion medium contained Krebs-Rin- ger buffer pH 7.4 rat erytrocites l/3 (v/v), BSA 4%, glucose O.l%, piruvic acid 15 mM,41eucine 5 mM, other amino aci$s at physiologic$l rat concen- tration, U C leu 0.0625 UC/ml and (His ( Me)). The (His ( Me)) causes an important reduction of the dpm incorporated into the secreted proteins. In the control shows t5at the rate of secretion was 1.21 + 0.16 mg/g/h. The addition of (His ( Me)) at 0.05, 0.1, 0.25, 0.5, 1.0 and 2 mM causes a reduction between 40 $0 60%, and the degree of inhibition is practically indipendent of the (His Me)) conc$ntration. We can conclude that, in controlled conditions, the (His ( Me)) inhibit the hepatic protein synthesis more than the hepatic protein secretion.

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