Studies on the production and assessment of experimental histidinemia in the rat.
Intraperitoneal administration to rats of D- or DL-alpha-hydrazinoimidazolylpropionic acid was found to produce a substantial inactivation of hepatic histidine ammonia-lyase (EC 4.3.1.3) in vivo. Proportional to this loss in enzyme activity was an impairment of the ability of treated rats to oxidize L-[ring-2-14C] histidine to 14CO2. Rats in which hepatic histidine ammonia-lyase activity was either depressed by DL-hydrazinoimidazolylproprionic acid injection or elevated by feeding a high protein diet displayed proportionately altered rates of 3H2O release into plasma water following L-[3-3H] histidine administration. Plasma L-histidine clearance following loading with this amino acid was similarly affected by these treatments. Administration of DL-alphal-hydrazinoimisazolylproprionic acid to rats was also found to inactivate non-specifically pyridoxal 5-phosphate enzymes in vivo; pyridoxine injection was found to reverse the DL-alpha-hydrazinoimidazolylproprionic acid-induced inactivation of hepatic aspartate aminotransferase (EC 2.6.1.1) in vivo, but not that of hepatic histidine ammonia-lyase. These findings demonstrate that histidine ammonia-lyase is the rate-limiting factor in L-histidine degradation in the rat. The potential usefulness of DL-hydrazinoimidazolylproprionic acid in the production of an animal model for histidinemia (hereditary histidine ammonia-lyase deficiency) is discussed.
D000642:Ammonia-Lyases / Q000378:metabolism*; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002364:Caseins / Q000378:metabolism; D004044:Dietary Proteins; D006639:Histidine / Q000031:analogs & derivatives / Q000097:blood* / Q000494:pharmacology; D006638:Histidine Ammonia-Lyase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007093:Imidazoles / Q000652:urine; D008099:Liver / Q000201:enzymology; D008297:Male; D011736:Pyridoxine / Q000494:pharmacology; D011773:Pyruvates / Q000652:urine; D051381:Rats; D000637:Transaminases / Q000378:metabolism; D014559:Urocanate Hydratase / Q000378:metabolism; D014867:Water / Q000378:metabolism
D002364:Caseins; D004044:Dietary Proteins; D007093:Imidazoles; D011773:Pyruvates; D014867:Water; D002245:Carbon Dioxide; D006639:Histidine; D000637:Transaminases; D014559:Urocanate Hydratase; D000642:Ammonia-Lyases; D006638:Histidine Ammonia-Lyase; D011736:Pyridoxine