Metabolic Studies of Vitamin K1-14C and Menadione-14C in the Normal and Hepatectomized Rats

Abstract

SummaryThe metabolism of vitamin K1- 14C and menadione-14C (vitamin K3-14C) was studied in normal and hepateetomized rats. After the administration of menadione, about 70% of the 14C was excreted in the urine in 24 hrs in both types of rats. Two urinary metabolites were identified by enzymatic hydrolysis: one a glucuronide and the other a sulfate of reduced menadione. Thus, the liver is not necessary for the metabolism of menadione. In the vitamin K1 studies, the intact rats excreted only 10% of the 14C and the hepatectomized rats excreted less than 0.5%. The retention of vitamin K1 may explain its superiority over menadione as an antidote for overdosages of oral anticoagulants.

Does the absence of ABCC6 (Multidrug Resistance Protein 6) in patients withPseudoxanthoma elasticumprevent the liver from providing sufficient vitamin K to the periphery?

“…Where menadione is produced is still unclear, as some investigators 33 do not find any conversion of K 1 into MK-4 in cell lines, while others 34 find some conversion in brain. The liver appears to be required for K 1 metabolism in the rat 35 and the possibility that the liver is a major menadione (or even MK-4) producer is not ruled out by the available data in our opinion. In any case, menadione can be taken up and converted into MK-4 by various cell types 33 and tissues also readily take up MK-4.…”

Determination of the urinary aglycone metabolites of vitamin K by HPLC with redox-mode electrochemical detection

“…We also confirmed in this study (data not shown) that incubation of urine with ␤-glucuronidase released the same two 5C-and 7C-aglycones and gave chromatograms identical to those after methanolic HCl hydrolysis. This does not exclude the possibility of other conjugates being present, because K 3 , which lacks the side chain, has been shown to be excreted as both glucuronide and the sulfate conjugates of the quinol form in rats (38,39) and rabbits (40). For routine quantitative analyses, we chose methanolic HCl over enzymic hydrolysis for reasons of its greater convenience and efficiency and to ensure the complete hydrolysis of all conjugates present.…”

Metabolism of Acetate to Amino Acids in Brains of Rats After Complete Hepatectomy

“…A three-stage procedure for complete removal of the liver in dogs was first described by Mann in 1921(Mann, 1921. Modifications of this technique have been described (Markowitz and Soskin, 1927;Grindlay and Mann, 1952;Starzl et al, 1959) and have been used extensively in this (Flock et al, 1963;Hazelrig et al, 1967;Losito et al, 1968;Tyce and Owen, 1979a,b) and other laboratories (Mc-Menamy et al, 1965). A modification of the technique has also been used in monkeys (Maddock and Svedburg, 1938).…”