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K L Kirk

Publications and source records attributed to K L Kirk.

160 records · Page 9Linked to original sources

Effect of 2-fluorohistidine upon leukocytopoiesis in mice.

Administrationof L-2-fluorohistidine to mice produces a dose and time dependent leukopenia, hypocellularity with reduction in hematopoiesis in the spleen and bone marrow, and depletion of lymphocytes in the spleen, lymph nodes and cortex of the thymus. The LD50 is 250 mg/kg at five days. The effect on hematopoetic tissue is nearly as great at non-leathal "therapeutic" doses. Effects on circulating erythrocyte and reticulocyte levels and the deposition of hemosiderin in the spleen are minimal. At non-leathal doses the effects of this amino acid analog appear to be completely reversible after 6 to 10 days.A description of the toxicity, histopathology and a discussion of the possible mechanisms of action are presented.

Animals↗

Histidine ammonia-lyase. The use of 4-fluorohistidine in identification of the rate-determining step.

The alpha,beta eliminations of NH3 from L-histidine and 4-fluoro-L-histidine by histidine ammonia-lyase appear to occur by similar mechanisms, although a large difference in Vmax for the two reactions was observed. Both reactions were shown to be reversible with an equilibrium constant of 4 to 5. The presteady state kinetics of the deamination of 4-fluoro-L-histidine indicates that the rate-determining step precedes the dissociation of ammonia from the enzyme. The isotope effect of 1.4 to 2.0 observed with 4-fluoro-DL-[beta-2-H2]histidine or DL-[beta-2-H2]histidine or DL-[beta-2-H2]histidine indicates that the C-H bond breakage is at least partially rate-determining for the deamination of both substrates.

Ammonia-Lyases↗