1.17.4.5 evolution VKORL1, EC 1.1.4.2, is more highly conserved among vertebrates than its evolutionary relative VKOR, EC 1.1.4.1. The human paralogous proteins are 42-60% identical 1.17.4.5 metabolism vitamin K cycle, overview 1.17.4.5 additional information conserved loop cysteines in VKOR are not required for active site regeneration after each cycle of oxidation. Missense mutations identified in the VKOR coding region, especially hotspot mutation at position 139, lead to a VKOR molecule more resistant to warfarin inhibition, thus requiring higher therapeutic warfarin doses 1.17.4.5 physiological function vitamin K dependent oxidative protection is independent of VKOR inhibition by warfarin and GGCX inhibition by 2-chloro-vitamin K1, which indicates that vitamin K plays potential physiological roles outside of the realm of carboxylation. The hVKORL1 turnover rate for vitamin K 2,3-epoxide reductase activity is significantly slower than for hVKOR, EC 1.1.4.1. the physiological role for VKORL1 reduction of vitamin K 2,3-epoxide is minimal