E. A. Newsholme

This outstanding text, written in a clear, concise and easy-to-read style, provides students with an in-depth explanation of how each metabolic pathway is directly related to physiology, pharmacology, and clinical medicine. Emphasis is given to those medical problems encountered most frequently in daily clinical practice. Basic metabolism is presented as a coherent part of physiology and reference is made to the matabaolic aberrations seen in clinical situations.

In alloxan-diabetes in the rat the uptake of glucose by heart and diaphragm muscle in vitro is impaired both in the absence and in the presence of insulin. The defect in glucose uptake in the absence of the hormone has been explained by the low rate of membrane transport of glucose in the insulin- deficient tissue (insulin accelerates the membrane transport of glucose); the defect in the membrane transport of glucose may be corrected by the addition of high concentrations of insulin in vitro but not by hypophysectomy or adrenalectomy (see Morgan, Cadenas, Regen & Park, 1961 b; Morgan, Regen, Henderson, Sawyer & Park, 1961 c; Kipnis, 1959). Two other defects cannot be ex- plained in this way: first, an impaired ability of low concentrations of insulin to stimulate membrane transport of glucose; and, secondly, a decreased rate of phosphorylation of glucose. These defects are corrected by hypophysectomy or adrenalectomy or by treatment of the diabetic rat -with insulin (Morgan et al. 1961b, c; Park et al. 1961; Kipnis, 1959; Riddick, Reisler & Kipnis, 1962); they can be restored in muscles of hypo--physectomized diabetic rats by treatment, of the animals with growth hormone and corticosteroids. The development of these defects in glucose meta- bolism in muscle in diabetes is thus favoured by a deficiency of circulating insulin together with a sufficiency of growth hormone and corticosteroids.

1. The activities of fructose 1,6-diphosphatase were measured in extracts of muscles of various physiological function, and compared with the activities of other enzymes including phosphofructokinase, phosphoenolpyruvate carboxykinase and the lactate-dehydrogenase isoenzymes. 2. The activity of phosphofructokinase greatly exceeded that of fructose diphosphatase in all muscles tested, and it is concluded that fructose diphosphatase could not play any significant role in the regulation of fructose 6-phosphate phosphorylation in muscle. 3. Fructose-diphosphatase activity was highest in white muscle and low in red muscle. No activity was detected in heart or a deep-red skeletal muscle, rabbit semitendinosus. 4. The lactate-dehydrogenase isoenzyme ratio (activities at high and low substrate concentration) was measured in various muscles because a low ratio is characteristic of muscles that are more dependent on glycolysis for their energy production. As the ratio decreased the activity of fructose diphosphatase increased, which suggests that highest fructose-diphosphatase activity is found in muscles that depend most on glycolysis. 5. There was a good correlation between the activities of fructose diphosphatase and phosphoenolpyruvate carboxykinase in white muscle, where the activities of these enzymes were similar to those of liver and kidney cortex. However, the activities of pyruvate carboxylase and glucose 6-phosphatase were very low in white muscle, thereby excluding the possibility of gluconeogenesis from pyruvate and lactate. 6. It is suggested that the presence of fructose diphosphatase and phosphoenolpyruvate carboxykinase in white muscle may be related to operation of the alpha-glycerophosphate-dihydroxyacetone phosphate and malate-oxaloacetate cycles in this tissue.