Introduction to Human Nutrition

150 Introduction to Human Nutrition

the large intestine, again into the lymphatic system,
cleared by the liver, and released in VLDLs. It is often
suggested that about half of the requirement for
vitamin K is met by intestinal bacterial synthesis, but
there is little evidence for this, other than the fact that
about half of the vitamin K in liver is phylloquinone
and the remainder a variety of menaquinones. It is
not clear to what extent the menaquinones are bio-
logically active. It is possible to induce signs of vitamin
K defi ciency simply by feeding a phylloquinone-defi -
cient diet, without inhibiting intestinal bacterial
action.
The synthetic compound menadiol is absorbed
largely into the hepatic portal system, and undergoes
alkylation in the liver to yield menaquinone-4, which
is released together with phylloquinone and other
menaquinones in VLDLs.

Metabolic functions of vitamin K

Although it has been known since the 1920s that
vitamin K was required for blood clotting, it was not
until the 1970s that its precise function was estab-

lished. It is the cofactor for the carboxylation of

glutamate residues in the postsynthetic modifi cation

of proteins to form the unusual amino acid γ-

carboxyglutamate, abbreviated to Gla (Figure 8.7).

In the presence of warfarin, vitamin K epoxide

cannot be reduced back to the active hydroquinone,

but accumulates and is excreted as a variety of conju-

gates. However, if enough vitamin K is provided in

the diet, the quinone can be reduced to the active

hydroquinone by the warfarin-insensitive enzyme,

and carboxylation can continue, with stoichiometric

utilization of vitamin K and excretion of the epoxide.

High doses of vitamin K are used to treat patients

who have received an overdose of warfarin, and at

least part of the resistance of some populations of rats

to the action of warfarin is due to a high consumption

of vitamin K from maram grass, although there are

also genetically resistant populations of rodents.

Prothrombin and several other proteins of the

blood clotting system (factors VII, IX and X, and

proteins C and S) each contain between four and

six γ-carboxyglutamate residues per mole. γ-Carboxy-

O

O

CH 3

3

n

O

O

CH 3

OH

OH

CH 3

O

O

CH 3

C

CH 3

O

C

CH 3

O

Phylloquinone (vitamin K 1 )

Menaquinone (vitamin K 2 )

Menadiol (vitamin K 3 ) Menadiol diacetate
(acetomenaphthone)

Figure 8.6 The vitamin K vitamers, phylloqui-

none (vitamin K 1 ), menaquinone (vitamin K 2 ), and

menadiol (a synthetic compound, vitamin K 3 ).