Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK-4 biosynthesis.
In contrast to other fat-soluble vitamins, dietary vitamin K is rapidly lost to the body resulting in comparatively low tissue stores. Deficiency is kept at bay by the ubiquity of vitamin K in the diet, synthesis by gut microflora in some species, and relatively low vitamin K cofactor requirements for γ-glutamyl carboxylation. However, as shown by fatal neonatal bleeding in mice that lack vitamin K epoxide reductase (VKOR), the low requirements are dependent on the ability of animals to regenerate vitamin K from its epoxide metabolite via the vitamin K cycle. The identification of the genes encoding VKOR and its paralog VKOR-like 1 (VKORL1) has accelerated understanding of the enzymology of this salvage pathway. In parallel, a novel human enzyme that participates in the cellular conversion of phylloquinone to menaquinone (MK)-4 was identified as UbiA prenyltransferase-containing domain 1 (UBIAD1). Recent studies suggest that side-chain cleavage of oral phylloquinone occurs in the intestine, and that menadione is a circulating precursor of tissue MK-4. The mechanisms and functions of vitamin K recycling and MK-4 synthesis have dominated advances made in vitamin K biochemistry over the last five years and, after a brief overview of general metabolism, are the main focuses of this review.
Centre for Haemostasis and Thrombosis, Guy's and St. Thomas' NHS Foundation Trust, London SE1 7EH, UK; and.
Martin J
MJ
Shearer
Paul
P
Newman
D000818:Animals; D053898:Biosynthetic Pathways; D004032:Diet; D004122:Dimethylallyltranstransferase / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D015394:Molecular Structure; D010837:Vitamin K 1 / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D024482:Vitamin K 2 / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D064417:Vitamin K Epoxide Reductases / Q000378:metabolism
D024482:Vitamin K 2; C016186:vitamin K1 oxide; C030814:menatetrenone; D010837:Vitamin K 1; D064417:Vitamin K Epoxide Reductases; D004122:Dimethylallyltranstransferase; C425464:UBIAD1 protein, human
UbiA prenyltransferase-containing domain 1; anticoagulants; menaquinones; phylloquinone; vitamin K antagonists; vitamin K dehydrogenase; vitamin K epoxide; vitamin K epoxide reductase; warfarin; warfarin resistance; γ-carboxyglutamate proteins