Studies on the production and assessment of experimental histidinemia in the rat |
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Authors: | Larry M Brand Alfred E Harper |
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Institution: | Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin, Madison, Wisc. 53706, U.S.A. |
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Abstract: | Intraperitoneal administration to rats of D- or DL-α-hydrazunoimidazolylpropionic acid was found to produce a substantial inactivation of hepatic histidine ammonia-lysase (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 histadine ammonia-lyase activity was either depressed by dl-hydrazunoimidazolylproprionic acid injection or elevated by feeding a high protein diet displayed proportionately altered rates of 3H2O release into plasma water following l-3-H]histidine administration. Plasma l-histidine clearance following loading with this amino acid was similarly affected by these treatments. Administration of dl-α-hydrazinoimisazolyl-proprionic acid to rats was also found to inactivate non-specifically pyridoxal 5-phosphate enzymes in vivo; pyridoxine injection was found to reverse the dl-α-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. |
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Keywords: | HIPA α-hydrazinoimidazolypropionic acid |
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