Comparison of glycolytic enzyme activities in a series of human and rodent hepatomas

Abstract

Activities of all the enzymes of the glycolytic pathway were determined under concordant conditions in a series of rat hepatomas of varying growth rates and in a group of human hepatomas. Similar determinations were done for comparison on normal human and rat livers. Human and rat liver on the whole are similar with respect to the glycolytic enzymes, both on an absolute and relative basis. In human liver the activities of glucose-6-phosphate dehydrogenase, glycerolphosphate dehydrogenase and fructose-1,6-diphosphatase are lower than in rat liver, while phosphoglucomutase is higher in the human tissue than in the rat tissue. Glucokinase of low glucose affinity was readily demonstrable in normal rat livers, but only glucokinase with high glucose affinity could be demonstrated in normal human livers. In a series of ten human hepato-cellular carcinomas an attempt was made to compare the abnormalities of glycolytic enzymes with those found in a series of slowly and rapidly growing rat hepatomas. Glucokinase and phosphofructokinase showed patterns similar to those of the slowly growing rat hepatomas, that is, levels similar to those found in normal liver. The majority of the human hepatomas had pyruvate kinase activities similar to those of the liver, a pattern that had also been found for the slowly growing rat hepatomas. Some of the human tumors had clearly increased pyruvate kinase levels, which are characteristic of rapidly growing rat hepatomas. Glycerolphosphate dehydrogenase was drastically reduced or absent in the human hepatomas in a pattern closely similar to that observed for the rapidly growing rat hepatomas. Fructose-diphosphatase was predominantly depressed in the human hepatomas similar to the finding in rapidly growing rat hepatomas. Glucose-6-phosphate dehydrogenase is either normal or elevated in both fast- and slow-growing rat hepatomas, but it is drastically reduced or absent in the majority of the human hepatomas. With respect to phosphoglucomutase the human hepatomas are similar to the fast-growing rat hepatomas showing generally quite low levels. Even within the group of the glycolytic enzymes, it is not possible to fit the abnormalities found in the human hepatomas uniformly into the pattern found in either the slowly or rapidly growing hepatomas. Extrapolation from the enzyme pattern of either type of rat hepatoma to the pattern of the human tumor, therefore, is quite uncertain and extrapolation to other types of human malignant tissues should not be attempted.