“Anaplerosis” means “to fill up” and refers to substrates and reactions that fill up a metabolic pathway as its own substrates leak out for other purposes. The citric acid cycle is a central example of this because its intermediates are often used to synthesize other components the cell needs. On a mixed diet where carbohydrate provides much of the energy, pyruvate serves as the main anaplerotic substrate. During carbohydrate restriction, protein takes over. Fat is the least anaplerotic of the macronutrients because the main product of fatty acid metabolism, acetyl CoA, is not directly anaplerotic. There are several very minor pathways that allow some anaplerosis from fat, but they are unlikely to eclipse the need for protein to support this purpose during carbohydrate restriction. Thus, carbs and protein are the two primary sources of anaplerosis. This means carbs can spare the need for protein, and that protein requirements rise on a carb-restricted diet.

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