In vivo regulation of muscle glycogen synthase and the control of glycogen synthesis.

The activity of glycogen synthase (GSase; EC 2.4.1.11) is regulated by covalent phosphorylation. Because of this regulation, GSase has generally been considered to control the rate of glycogen synthesis. This hypothesis is examined in light of recent in vivo NMR experiments on rat and human muscle and is found to be quantitatively inconsistent with the data under conditions of glycogen synthesis. Our first experiments showed that muscle glycogen synthesis was slower in non-insulin-dependent diabetics compared to normals and that their defect was in the glucose transporter/hexokinase (GT/HK) part of the pathway. From these and other in vivo NMR results a quantitative model is proposed in which the GT/HK steps control the rate of glycogen synthesis in normal humans and rat muscle. The flux through GSase is regulated to match the proximal steps by "feed forward" to glucose 6-phosphate, which is a positive allosteric effector of all forms of GSase. Recent in vivo NMR experiments specifically designed to test the model are analyzed by metabolic control theory and it is shown quantitatively that the GT/HK step controls the rate of glycogen synthesis. Preliminary evidence favors the transporter step. Several conclusions are significant: (i) glucose transport/hexokinase controls the glycogen synthesis flux; (ii) the role of covalent phosphorylation of GSase is to adapt the activity of the enzyme to the flux and to control the metabolite levels not the flux; (iii) the quantitative data needed for inferring and testing the present model of flux control depended upon advances of in vivo NMR methods that accurately measured the concentration of glucose 6-phosphate and the rate of glycogen synthesis.

Geographic and climatic control of primate diversity.

Although the comparative ecology of primates has been relatively well studied and there have been a number of outstanding studies of individual primate communities, the factors determining primate species diversity on either a local or regional level are largely unexplored. Understanding the determinants of species abundance is an important aspect of biodiversity and is critical for interpreting the comparative ecology of these different communities and for designing effective strategies of conservation. Comparative analysis of species diversity in more than 70 primate communities from South America, Africa, Madagascar, and Asia shows that on major continental areas and large tropical islands, there is a high positive correlation between the number of primate species and the area of tropical forest. Within major continental areas, the species diversity at individual sites is highly correlated with mean annual rainfall for South America, Africa, and Madagascar, but not Asia.