Modeling biochemical aspects of energy metabolism in mammals.

A framework representing the major biochemical pathways of nutrient metabolism is developed allowing quantification of the energy efficiency of different nutritional scenarios. The model is based on a number of carbon chain pivots (glucose, pyruvate, acetyl coenzyme A, alpha-ketoglutarate, oxaloacetate and serine) and cofactors involved in metabolism. Excess pivots yield acetyl coenzyme A, which may be used for ATP or lipid synthesis. In contrast to previous work of this kind, the framework was constructed so that new insights in nutrient metabolism can be easily incorporated. Traditionally, integral values have been used to quantify mitochondrial ATP synthesis from cofactors (i.e., 3 ATP/NADH and 2 ATP/FADH(2)), but current estimates are approximately 0.20 lower than previously assumed. Based on the latter, the energy expenditure for ATP synthesis from glucose was 91.0 kJ/ATP. For lipid (tripalmitin), 96.3 kJ/ATP was required whereas for amino acids energy expenditures varied between 99.2 (glutamate) and 153.2 kJ/ATP (cysteine). Energy derived from amino acid catabolism is stored and transferred either via carbon chain pivots or cofactors. It is hypothesized that this may affect the ultimate utilization of this energy (e.g., for ATP or lipid synthesis). The energy cost of nitrogen transport appeared relatively modest for most nonessential amino acids. Likewise, the net cost of using dietary glutamate and glutamine for ATP synthesis (e.g., in the viscera) and de novo synthesis of these amino acids in muscle is relatively minor and of similar magnitude as the cost of storing glucose energy as glycogen.