Kappadione

Menadione or 2-methyl-1,4-naphthoquinone is a synthetic vitamin K analog, undergoes 1-electron reduction by enzymes such as microsomal NADPH–cytochrome P450 reductase and mitochondrial NADH–ubiquinone oxidoreductase (complex I), resulting in redox cycling, or it detoxification via two-electron reduction by NAD(P)H–quinone oxidoreductase ^A32072. Vitamin K is a group of lipophilic, hydrophobic vitamins that exist naturally in two forms (and in 3 synthetic forms): vitamin K1, which is found in plants, and vitamin K2, which is synthesized by bacteria. Vitamin K is an important dietary component because it is necessary as a cofactor in the activation of vitamin K dependent proteins. Metabolism of vitamin K occurs mainly in the liver. In the first step, vitamin K is reduced to its quinone form by a quinone reductase such as NADPH dehydrogenase. Reduced vitamin K is the form required to convert vitamin K dependent protein precursors to their active states. It acts as a cofactor to the integral membrane enzyme vitamin K-dependent gamma-carboxylase (along with water and carbon dioxide as co-substrates), which carboxylates glutamyl residues to gamma-carboxy-glutamic acid residues on certain proteins, activating them. Each converted glutamyl residue produces a molecule of vitamin K epoxide, and certain proteins may have more than one residue requiring carboxylation. To end the cycle, the vitamin K epoxide is returned to vitamin K via the vitamin K epoxide reductase enzyme, also an integral membrane protein. The vitamin K dependent proteins include various important coagulation factors, such as prothrombin. Warfarin and other coumarin drugs act as anticoagulants by blocking vitamin K epoxide reductase ^L1568.

Vitamin K is heavily metabolized in the liver and excreted in the urine and bile. In tracer studies, it was found that approximately 20% of an injected dose of phylloquinone (Vitamin K metabolite) was found in the urine whereas about 40-50 % was excreted in the feces via the biliary system. The proportion of drug excreted was the same regardless of whether the injected dose was 1 mg or 45 µg. It can, therefore, be inferred that about 60-70% percent of the amounts of phylloquinone absorbed from each vitamin-K containing meal will be lost to the body by excretion ^L1570. Two major human excretion products have been identified: carboxylic acids with 5 and 7-carbon sidechains that are excreted in the urine as glucuronide conjugates. The biliary metabolites have not been clearly identified but are initially excreted as water-soluble conjugates and become lipid soluble during their passage through the gut, probably through deconjugation by the gut flora. There is no evidence for body stores of vitamin K being conserved by an enterohepatic circulation. Vitamin K itself is too lipophilic to be excreted in the bile and the sidechain-shortened carboxylic acid metabolites are not biologically active ^L1570.