Regulation of enzyme levels in the blood. Influence of environmental and genetic factors on enzyme clearance.

Since its discovery, lactic dehydrogenase virus (LDV) has remained unique as a model of long-term enzyme elevation due to impairment of enzyme clearance. The present study shows that mice inoculated with silica develop an increase in plasma lactate dehydrogenase (LDH) lasting for at least 6 months and that the enzyme elevation is due, at least in part, to impairment of clearance. The extent of the enzyme elevation is dependent on both the dose and route of silica administration and mice that had received both silica and LDV showed a more profound impairment of LDH clearance than mice that had received silica or LDV alone. Examination of the factors that regulate circulating enzyme levels in normal mice revealed that whereas there was no difference in resting enzyme levels among several inbred strains of mice (BALB/cAnN, NZBWF1/J,B10.D2/nSnN, and A/J mice), when mice were stressed by the administration of an enzyme load, certain inbred strains (BALB/cAnN) cleared the enzyme rapidly and others (B10.D2/nSnN) cleared the enzyme slowly. Moreover, in B10.D2/nSnN mice, enzyme clearance was age-related. When different strains of mice were infected with LDV, LDH levels were substantially higher in the circulation of slow enzyme clearers as compared to rapid enzyme clearers. It is concluded that both environmental and genetic factors influence the clearance of LDH and that impairment of enzyme clearance may be a more important factor than previously suspected in regulating enzyme levels in disease states.