Estimation of the Fractional Catabolic Rate Constants for the Elimination of Cytosolic Liver Enzymes From Plasma

Abstract

Pathological elevations of the plasma activities of liver enzymes are not simply related to the quantitative release of such enzymes from the liver. Several enzymatic indices, such as the well-known de Ritis quotient, may be determined by differences in the time course of hepatic enzyme release, rather than reflecting true differences in the released quantities of various enzymes. A more quantitative use of enzymatic data is hampered by the fact that the fractional catabolic rate constants for the elimination of enzyme activities from plasma are unknown. In the present study, three of these constants are estimated by comparison of the time-activity curves in plasma with the corresponding curve of a simultaneously released, more slowly eliminated reference enzyme. This method can be applied in patients with an acute short period of hepatic enzyme release. Values obtained for the cytosolic isoforms of lactate dehydrogenase, AST and ALT are: fractional catabolic rate constant (lactate dehydrogenase isoenzyme 5) = 0.13 +/- 0.01 hr-1, fractional catabolic rate constant (cytosolic AST) = 0.088 +/- 0.016 hr-1 and fractional catabolic rate constant (cytosolic ALT) = 0.034 +/- 0.004 hr-1 (mean +/- S.E., n = 10). These values are much higher than the apparent disappearance rate constants, because of extravascular return of activity and tailing release of enzymes during the major part of the elimination phase. It is shown that these results are consistent with earlier published data on the disappearance rates from plasma of lactate dehydrogenase, AST and ALT after acute liver injury. Cumulative release of various cytosolic enzymes occurred in proportion to the corresponding activities in human control livers.

Use of Hy's Law and a New Composite Algorithm to Predict Acute Liver Failure in Patients With Drug-Induced Liver Injury

“…The AST half-life (mostly cytoplasmic) is shorter (about 8 hours) than that of ALT (about 21 hours). 32 the reliability of predicting ALF risk since there is clearly a tendency for the liver injury pattern to shift to cholestatic/mixed status. This tendency has also been observed previously.…”

Rat Liver Enzyme Release Depends on Blood Flow‐Bearing Physical Forces Acting in Endothelium Glycocalyx rather than on Liver Damage

“…The rate of enzyme release into the perfusates from isolated liver was calculated by means of the kinetics Enzfitter Program, based on the consideration of the simultaneity of enzyme release observed in isolated liver preparations [28]. Significance of the differences between groups was analysed by two-way ANOVA and, in case of significance, Student's t -test was applied.…”

The role of calcium and nitric oxide during liver enzyme release induced by increased physical forces as evidenced in partially hepatectomized rats

“…The rate of enzyme release into the perfusates from isolated liver was calculated by means of the kinetics EnzFitter program (Biosoft, Cambridge, UK), based on the consideration of the simultaneity of enzyme release observed in isolated liver preparations 5. Significance of the differences between groups was analyzed by 2‐way analysis of variance and, in case of significance, a Student t test was applied.…”

“…In fact, this phenomenon usually follows a respective gradient of concentration between an organ, such as the liver, and the blood compartments 2‐4. Moreover, values of released enzymes are much higher than the apparent disappearance rates constants and are consistent akin to decreasing concentration levels within the plasma, as reported for lactate dehydrogenase (LDH) and aspartate (AST) and alanine (ALT) aminotransferases after acute liver injury 5. However, the mechanisms controlling cellular enzyme release remain poorly understood.…”