Since
gamma-carboxyglutamic acid (Gla) in Gla-containing
proteins is stoichiometrically excreted into urine as free Gla, urinary Gla excretion is believed to reflect the rate of synthesis and degradation of
vitamin K-dependent
proteins and the utilization of
vitamin K in body. We studied the daily changes in urinary Gla excretion and plasma
vitamin K-dependent
clotting factor levels in rats fed
vitamin K-deficient diets followed by
subcutaneous injection of
vitamin K1 or after the
oral administration of
Warfarin. Urinary Gla excretion in normal rats fed a standard diet that contained about 500 ng of
vitamin K1 per gram of diet was 2.35 +/- 0.25 mumoles/day, but the level in rats fed a markedly
vitamin K-deficient diet (less than 5 ng/g) decreased to 1.40 +/- 0.14 mumoles/day. When rats were fed a moderately
vitamin K-deficient diet (20-50 ng/g), plasma
vitamin K-dependent
clotting factor levels decreased significantly, but urinary Gla excretion did not decrease.
Warfarin, a
vitamin K antagonist, caused a significant decrease in urinary Gla excretion and plasma
clotting factor levels. When
vitamin K, (200 micrograms/kg) was injected subcutaneously in rats fed a markedly
vitamin K-deficient diet, the plasma
vitamin K-dependent
clotting factor levels recovered quickly to normal, but urinary Gla excretion showed only a partial recovery to 1.74 +/- 0.15 mumoles/day. These results indicate that urinary Gla excretion decreases in
vitamin K deficiency, but changes in urinary Gla excretion do not reflect
vitamin K deficiency in rats as sensitively as changes in the prothrombin time and plasma K-dependent
clotting factor levels.