This study was undertaken to search for the endogenous dithiol cofactor of the reductases of the vitamin K cycle. As a starting point, the redox-active lipophilic endogenous compounds lipoic acid and lipoamide were looked at. The study shows that microsomes contain NADH-dependent lipoamide reductase activity. Reduced lipoamide stimulates microsomal vitamin K epoxide reduction with kinetics comparable with those for the synthetic dithiol dithiothreitol (DTT). Reduced lipoic acid shows higher (4-fold) Km values. No reductase activity with lipoic acid was found to be present in microsomes or cytosol. The reduced-lipoamide-stimulated vitamin K epoxide reductase is as sensitive to warfarin and salicylate inhibition as is the DTT-stimulated one. Both vitamin K epoxide reductase and lipoamide reductase activity are recovered in the rough microsomes. NADH/lipoamide-stimulated vitamin K epoxide reduction is uncoupled by traces of Triton X-100, suggesting that microsomal lipoamide reductase and vitamin K epoxide reductase are associated. The results suggest that the vitamin K cycle obtains reducing equivalents from NADH through microsomal lipoamide reductase.
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January 1994
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Research Article|
January 15 1994
Microsomal lipoamide reductase provides vitamin K epoxide reductase with reducing equivalents Available to Purchase
H H W Thijssen;
H H W Thijssen
1Department of Pharmacology, University of Limburg, Maastricht, The Netherlands
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Y P G Janssen;
Y P G Janssen
1Department of Pharmacology, University of Limburg, Maastricht, The Netherlands
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L T M Vervoort
L T M Vervoort
1Department of Pharmacology, University of Limburg, Maastricht, The Netherlands
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Publisher: Portland Press Ltd
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 1994 The Biochemical Society, London
1994
Biochem J (1994) 297 (2): 277–280.
Citation
H H W Thijssen, Y P G Janssen, L T M Vervoort; Microsomal lipoamide reductase provides vitamin K epoxide reductase with reducing equivalents. Biochem J 15 January 1994; 297 (2): 277–280. doi: https://doi.org/10.1042/bj2970277
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