Fig. 11.

Glucose, fatty acids and calcium in skeletal muscle. The transport of glucose is shown to be affected by insulin, wortmannin, and caffeine, through the kinase akt (also known as protein kinase B). The latter is stimulated by phosphorylation through the activation of PI3K, stimulated by insulin, but inhibited by wortmannin and caffeine. Caffeine also stimulates Ca²⁺ release from the sarcoplasmic reticulum. An elevation of Ca²⁺ is also elicited by the selective ionophore ionomycin.Ca²⁺ has known stimulation points at glycogen phosphorylase, CaMKK, and α-Ketoglutarate dehydrogenase (αKGDH) which in turn activates the Krebs Cycle. The activation of AMPK by AMP and LKB1 is shared by CaMKK, although as indicated by the question mark, as the metabolic effects that would be exerted through AMPK on both glucose transport and fatty acid oxidation were not apparent in the present study. The connection between glucose and fatty acid metabolism is at malonyl-CoA, which inhibits the formation of the fatty acid-carnitine ester needed for transport and subsequent oxidation in the mitochondrion. The figure indicates inhibitory points as lines terminating in a perpendicular line; dotted arrows with plus signs indicate allosteric activation. Double lined arrows indicate transformations other than metabolic conversion, such as binding to elicit Ca²⁺ release or covalent activation through phosphorylation. Single arrows indicate metabolic transformation. The bidirectional arrows indicate near equilibrium reactions at lactate dehydrogenase and glucose phosphate isomerase. Also shown is the step catalyzing decarboxylation of the malonyl CoA back to acetyl CoA; this is the malonyl CoA carboxylase, abbreviated as MCD. Exogenous substrates (glucose and palmitate) are indicated in boxes.