Considerations of Veristic and Quasi-biological Activities for Coenzyme Q and Vitamins E and K

CONSIDERATIONS OF VERISTIC AND QUASI-BIOLOGICAL ACTIVITIES FOR COENZYME Q AND VITAMINS E AND K ARTHUR F. WAGNER AND KARL FOLKERS* The coenzyme Q group of compounds was elucidated just over five years ago. Their biochemical significance received prompt attention in vitro, but biological research on experimental animals and medical research have progressed more slowly. As in vivo animal data become available , however, a new facet of activity relationships between coenzyme Q and vitamins E and K is apparent, and a new appraisal ofthe literature is timely. It has been well known that the activities of the coenzyme Q and vitamins E and K groups are shared by the several structurally related compounds in each group. Today, it becomes strikingly apparent that members ofthe coenzyme Q and vitamins E and K groups have certain biological activities in common. For example, coenzyme Q and vitamin K both function [i] as cofactors ofa steroidal i-dehydrogenase; a-tocopherol and the 6-chromanol of hexahydrocoenzyme Q4 both greatly extend [2] the motility ofsperm; a 6-chromanol of the coenzyme Q group is apparently active in preventing [3] the gestation-résorption syndrome in the tocopherol-deficient rat; and the 6-chromanol ofhexahydrocoenzyme Q4 and a-tocopherol exhibit similar biological activity in the anemic and dystrophic monkey [4]. If these exemplary activities do not entirely reflect an antioxidant property or another non-specific functional characteristic of these compounds, the following question may be asked. When compounds ofthe E, K, and Q groups exhibit a similar biological activity , should the activity ofeach group be defined according to the intrinsic or extrinsic relationship ofeach group to the biologicalsystem? Considera- * Merck Sharp & Dohme Research Laboratories Division, Merck & Co., Inc., Rahway, New Jersey. This paper is contribution XL in the Coenzyme Q Series. 347 tion of this question may lead one to designate an activity as veristic (true) when the compound is intrinsically functional; in contrast, the activity may be considered as quasi (similar) when the compound is extrinsically functional. To demonstrate the principle, consider thiamine, which is an essential dietary factor for man and the lower animals; its role in man and experimental animals is considered intrinsically functional. The development ofthis consideration for the E, K, and Q groups is described herein since the over-all interpretation may reorientand stimulate research. The results ofrecent studies [i] with Bacillus sphaericus provide a sound basis to illustrate veristic and quasi activities in the K and Q groups. The cells of B. sphaericus contain vitamin K2(3S); this compound apparently functions as a cofactor for a steroidal i-dehydrogenase which converts appropriate substrates into corresponding A'^-dienone analogs. It has beenestablished beyond doubt thatB. sphaericus does not containa member of the coenzyme Q group, but it is noteworthy that a member of the coenzyme Q group has shown coenzymic activity comparable to that of vitamin K2(35) in the cell-free system. Therefore, one may say that vitamin Kj(35) has veristic activity in this dehydrogenase system because it is native to B. sphaericus and appears to have an intrinsically fundamental role. On the other hand, one may say that coenzyme Q has a comparable but quasi activity since coenzyme Q is not native to these cells and thus is extrinsically functional. If there can be one such example of quasi activity for coenzyme Q in a biological system, might there not be other such examples of quasi activity for E, K, and Q in vitro and, especially, in vivo? In view ofthis possibility, it would appear that in vitro and in vivo data on common biological activities in the E, K, and Q groups should be re-interpreted on the basis ofsuch considerations ofveristic and quasi activity. The interpretation of data on the apparent veristic and quasi activity of K and Q, respectively, in the B. sphaericus system is clear-cut, and in general the interpretation of data from microbial systems will be relatively simple. Considerable difficulty, however, may be anticipated in interpreting data fromanimaland human studies because oftheir greater complexity. Therefore , the relationship between a compound and a system may frequently be more definite in a microorganism than in an animal or human. It is important to recognize this difference...