Metabolic Differentiation of Distinct Muscle Types at the Level of Enzymatic Organization

Abstract

Activity levels of glycogen phosphorylase, hexokinase, triosephosphate dehydrogenase, lactate dehydrogenase, citrate synthase, 3‐hydroxyacyl‐CoA dehydrogenase, glycerolphosphate dehydrogenase (mitochondrial), and hexosediphosphatase have been determined in white (fast) muscles, red (slow) muscles, heart and smooth muscle of higher animals. The activities of these enzymes are taken as relative measures of metabolic capacities. Their ratios are interpreted as representing relations of different metabolic pathways or systems. In all muscles investigated comparable ratios exist for phosphorylase/triosephosphate dehydrogenase (glycogenolysis/glycolysis), glycerolphosphate dehydrogenase/triosephosphate dehydrogenase (mitochondrial glycerolphosphate oxidation/glycolysis), triosephosphate dehydrogenase/lactate dehydrogenase (glycolysis/lactate fermentation), hexokinase/citrate synthase (glucose phosphorylation/citric acid cycle) and 3‐hydroxyacyl‐CoA dehydrogenase/citrate synthase (fatty acid oxidation/citric acid cycle). With respect to the constancy of these ratios, consistent characteristics exist in the organization of the enzyme activity pattern. It is suggested that the more or less invariable coordination of these metabolic systems is not subject to metabolic differentiation. On the contrary, metabolic differentiation is reflected by extreme variations of the following ratios: triose‐phosphate dehydrogenase/3‐hydroxyacyl‐CoA dehydrogenase (glycolysis/fatty acid oxidation), triosephosphate dehydrogenase/citrate synthase (glycolysis/citric acid cycle), lactate dehydrogenase/citrate synthase (lactate fermentation/citric acid cycle), phosphorylase/hexokinase (glycogenolysis/glucose phosphorylation), and hexosediphosphatase/hexokinase (gluconeogenesis/glucose phosphorylation). These variable enzyme activity ratios are discriminative magnitudes and make it possible to discern distinct metabolic types of muscle. White (fast) muscle is characterized by high capacities of glycogenolysis, glycolysis and lactate fermentation, whereas the capacities of glucose phosphorylation, citric acid cycle and fatty acid oxidation are low. Red (slow) muscles, heart and smooth muscle show inverse characteristics. In white (fast) muscle, high activities of hexosediphosphatase and of mitochondrial glycerolphosphate dehydrogenase indicate that gluconeogenesis starting from glycerolphosphate or triosephosphate is probably important in this muscle type, and compensates for its low capacity of glucose phosphorylation.