Harper's Illustrated Biochemistry, Volume 1 - Murray R. 1993

Bioenergetics and Metabolism of Carbohydrates and Lipids
Regulation of Lipid Metabolism and Energy Sources in Tissues
Economics of Carbohydrate and Lipid Metabolism in the Organism

Glucose Demand

Many details of the interplay between carbohydrate and Lipid METABOLISM IN various Tissues are well understood. Under optimal nutritional conditions, The conversion of glucose into fat proceeds readily. Fat (triacylglycerol), with the exception of its glycerol moiety, cannot be converted into glucose (see above). Certain tissues and Cells—most notably Central Nervous system cells and erythrocytes—depend far more heavily on a continuous supply of glucose than others. A minimum amount of glucose is also likely required by extrahepatic tissues for the proper functioning of The Citric Acid Cycle. Furthermore, glucose appears to serve as the primary source of glycerol-3-phosphate in tissues lacking glycerokinase. A baseline (minimum) level of glucose oxidation is essential for cellular function. Substantial quantities of glucose are required to support fetal development and milk production. A series of regulatory mechanisms, alongside Gluconeogenesis, guarantees an adequate glucose supply during periods of shortage, with glucose sparing through alternative substrates playing a crucial role.

Preferential Utilization of Ketone Bodies and Free Fatty acids

Ketone bodies and free fatty acids spare glucose in Muscle tissue by indirectly inhibiting its cellular uptake, its phosphorylation to glucose-6-phosphate, as well as The activity of Phosphofructokinase and The oxidative decarboxylation of Pyruvate. The oxidation of free Fatty Acids and ketone bodies elevates intracellular citrate concentrations, which in turn inhibits phosphofructokinase. These findings, supported by perfusion experiments in isolated hearts showing that acetoacetate is oxidized in preference to fatty acids, align with the Conclusion that when carbohydrate availability is limited, potential Energy Sources are oxidized in the following order: (1) ketone bodies (and possibly other short-chain fatty acids, such as acetate), (2) free fatty acids, (3) glucose. This does not imply that the oxidation of one energy source completely halts the oxidation of others (Fig. 28.8). The mechanisms governing this hierarchical use of energy sources are particularly critical in tissues with a high capacity for aerobic Fatty acid oxidation (such as The Heart and slow-twitch muscle fibers), while playing a less significant role in tissues with low oxidative capacity, such as fast-twitch muscle fibers.

The combination of the glucose-sparing effect in skeletal and cardiac muscle induced by free fatty acids, and the inhibitory effect on free fatty acid mobilization in adipose tissue driven by the spared glucose, is known as the "glucose-fatty acid cycle".