Studies of the influence of portacaval shunt on the metabolism of tyrosine
Ali, F.M.; Ansley, J.; Faraj, B.A.
Journal of Pharmacology and Experimental Therapeutics 214(3): 546-553
1980
ISSN/ISBN: 0022-3565 PMID: 6105203 Document Number: 154361
In dogs with portacaval shunt, hypertyrosinemia could result from a decreased rate of tyrosine degradation by hepatic tyrosine transaminase or from failure of tyrosine to reach this enzyme. Fasting plasma tyrosine in shunted dogs (89 .+-. 10 .mu.mol/l) was significantly higher (P < 0.05) than in control or sham-operated dogs (45 .+-. 5 .mu.mol/l). Tyrosine transaminase activity in shunted dogs (0.50 .+-. 0.11 .mu.mol of [4-3H] hydroxyphenylpyruvic acid (PHPA)/mg of protein per h or 52.8 .+-. 6.5 .mu.mol PHPA/g of liver per h) was significantly higher (P < 0.05) than in control or sham dogs (0.22 .+-. 0.05 .mu.mol of PHPA/mg of protein per h or 23.6 .+-. 3.1 .mu.mol of PHPA/g of liver per h). The influence of portacaval shunt on the metabolism of i.v. administered tyrosine was also studied. After an i.v. injection of [3H] tyrosine (10 mg/kg, 200 .mu.Ci) in control dogs, there was a rapid initial decline in plasma tyrosine followed by a slower decline (.beta.-phase) with an average t1/2 [half-life] of 90 .+-. 11.5 min. Shunted dogs demonstrated a considerable decrease in the clearance rate and metabolism of plasma tyrosine as reflected by a 2-fold increase in plasma t1/2 (.beta.-phase) and in certain pharmacokinetic parameters (estimated areas under the curve, 18,125 .+-. 1121 vs. 8720 .+-. 571 .mu.mol .times. min .times. liter-1; total body clearance, 122.5 .+-. 14.7 vs. 60.0 .+-. 10.11 ml/min). A difference in ratio of tyrosine metabolic products was noted as well. In dogs with portacaval shunt, decreased metabolism of tyrosine and resultant tyrosinemia appear to result from reduced nutrient hepatic flow and not from loss of the holoenzyme.