Two enzymes catalyze vitamin K 2,3-epoxide reductase activity in mouse: VKORC1 is highly expressed in exocrine tissues while VKORC1L1 is highly expressed in brain.
VKORC1 and VKORC1L1 are enzymes that both catalyze the reduction of vitamin K2,3-epoxide via vitamin K quinone to vitamin K hydroquinone. VKORC1 is the key enzyme of the classical vitamin K cycle by which vitamin K-dependent (VKD) proteins are γ-carboxylated by the hepatic γ-glutamyl carboxylase (GGCX). In contrast, the VKORC1 paralog enzyme, VKORC1L1, is chiefly responsible for antioxidative function by reduction of vitamin K to prevent damage by intracellular reactive oxygen species. To investigate tissue-specific vitamin K 2,3-epoxide reductase (VKOR) function of both enzymes, we quantified mRNA levels for VKORC1, VKORC1L1, GGCX, and NQO1 and measured VKOR enzymatic activities in 29 different mouse tissues. VKORC1 and GGCX are highly expressed in liver, lung and exocrine tissues including mammary gland, salivary gland and prostate suggesting important extrahepatic roles for the vitamin K cycle. Interestingly, VKORC1L1 showed highest transcription levels in brain. Due to the absence of detectable NQO1 transcription in liver, we assume this enzyme has no bypass function with respect to activation of VKD coagulation proteins. Our data strongly suggest diverse functions for the vitamin K cycle in extrahepatic biological pathways.
Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, 53105 Bonn, Germany.
Michael
M
Caspers
Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, 53105 Bonn, Germany.
Katrin J
KJ
Czogalla
Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, 53105 Bonn, Germany.
Kerstin
K
Liphardt
Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, 53105 Bonn, Germany.
Jens
J
Müller
Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, 53105 Bonn, Germany.
Philipp
P
Westhofen
Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, 53105 Bonn, Germany. Electronic address: Matthias.Watzka@ukb.uni-bonn.de.
Matthias
M
Watzka
Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, 53105 Bonn, Germany. Electronic address: johannes.oldenburg@ukb.uni-bonn.de.
Johannes
J
Oldenburg
D000818:Animals; D001921:Brain / Q000378:metabolism; D019735:Carbon-Carbon Ligases / Q000235:genetics / Q000378:metabolism; D005088:Exocrine Glands / Q000378:metabolism; D005260:Female; D008099:Liver / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008861:Microsomes / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D014812:Vitamin K / Q000378:metabolism; D064417:Vitamin K Epoxide Reductases / Q000235:genetics / Q000378:metabolism*
D008565:Membrane Proteins; D012333:RNA, Messenger; D014812:Vitamin K; C000597964:VKORC1 protein, mouse; D064417:Vitamin K Epoxide Reductases; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase
NAD(P)H:quinone oxidoreductase 1 (NQO1); vitamin K 2,3-epoxide reductase (VKOR); vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1); vitamin K 2,3-epoxide reductase complex subunit 1-like 1 (VKORC1L1); γ-glutamyl carboxylase (GGCX)