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Unlike other amino acids, Gla
cannot be re-used once it has been formed. So after protein degradation,
free Gla will enter the circulation to be excreted via the urine.
On the basis of nutritional vitamin K intake and urinary Gla excretion
it may be calculated that in mammals the number of carboxylation
events exceeds the number of available vitamin K molecules ~ thousand
fold. Therefore, the KO formed must be recycled, which is accomplished
by an enzyme known as KO-reductase (see figure
1).
It can be seen that two reduction steps are required
to recycle one molecule of KO into KH2, and the oxidation of dithiols
provide the energy for both steps. In case KO-reductase has been
blocked (see below), a second enzyme (NADPH-dependent K-reductase,
also known as DT-diaphorase) may take over the generation of KH2.
Via this pathway only vitamin K quinone, and not the epoxide can
be converted into the hydroquinone. Hence vitamin K cannot be recycled,
which increases its nutritional requirement well above the normal
dietary intake.
Figure 1: The vitamin K cycle. Vitamin K is
ingested via the diet in the form of vitamin K quinone (K) and must
be converted into the hydroquinone (KH2) before being active as
a cofactor for carboxylase. The oxidation of KH2 into vitamin K-epoxide
(KO) provides the energy that drives the carboxylation reaction.
KO can be reduced by KO-reductase, but not by DT-diaphorase.
Recommended
literature:
- Suttie,
J.W. Vitamin K-dependent carboxylase.
Annu. Rev. Biochem.
54 (1985) 459-477.
- Vermeer,
C. Gamma-carboxyglutamate-containing
proteins and the vitamin K-dependent carboxylase.
Biochem. J. 266 (1990) 625-636.
- Li, T., Chang, C.-Y.,
Jin, D.-Y., Lin, P.-J., Khvorova, A., Stafford, D.W. (2004). Identification
of the gene for vitamin K epoxide
reductase. Nature 427, 541-544.
- Rost,
S., Fregin, A., Ivaskevicius,
V., Conzelmann, E., Hörtnagel,
K., Peiz, H.-J., Lappegard,
K., Selfried, E., Scharrer,
I., Tuddenham, E.G.D., Müller,
C.R., Strom, T.M., Oldenburg, J. (2004). Mutations in VKORC1 cause
warfarin resistance and multiple coagulation
factor deficiency type 2. Nature 427, 537-541.
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