Protein-Energy Interactions (International Dietary Energy Consultative Group - IDECG, 1991, 437 pages): Nutrition of immune cells: The implications for whole body metabolism: 10. Branched-point sensitivity, substrate cycles and thermogenesis

Protein-Energy Interactions (International Dietary Energy Consultative Group - IDECG, 1991, 437 pages)

Nutrition of immune cells: The implications for whole body metabolism

		(introductory text...)
		1. Introduction
		2. An introduction to metabolic-control logic and its application to the structure of a biochemical pathway
		3. Use of maximum activities of enzymes as quantitative indices of maximum flux through metabolic pathways
		4. Enzyme activities as indication of the capacity of major energy providing pathways in immune cells
		5. Glutamine and the immune cells
		6. Glutamine - A link between muscle and the immune system
		7. Large decreases in the concentration of glutamine in plasma
		8. The clinical significance of the role of glutamine in immune cells
		9. The effects of glutamine provision for the patient
		10. Branched-point sensitivity, substrate cycles and thermogenesis
		References

10. Branched-point sensitivity, substrate cycles and thermogenesis

Branched-point sensitivity provided by the glutamine pathway in immune cells may be vitally important for control. It is also possible that it expends energy. However, how much energy is expended to maintain such branched-point sensitivity in these cells is not known. Thus, the maintenance of the plasma glutamine concentration via synthesis and release from muscle will require energy but whether branched-point sensitivity imposes a rate of metabolism that is high and energy-demanding, is unclear. Thus, the high rate of glycolysis in tumour cells and in immune cells has been proposed by the author to provide branched-point sensitivity (NEWSHOLME et al., 1985a; b).

The process involves the conversion of glucose to lactate and unless lactate can be completely oxidised by other tissues it will be converted to glucose in liver. The conversion of glucose to lactate in one tissue (immune cells) and re-conversion to glucose in the liver is known as the Cori cycle and is equivalent to a large inter-tissue substrate cycle. It therefore leads to expenditure of energy. Its quantitative importance in energy expenditure is still uncertain, but it may be quite large.

Further work is needed on the fate of the end-products of the glutamine pathway in the immune cells. It is possible that if glutamate, aspartate and alanine, which may be released by immune cells, are reconverted to glutamine in other tissues, such as muscle or liver, the extra energy expenditure required for these biosynthetic processes could be high. It is also possible that only a small proportion is recycled, and most of these end-products are converted to glucose and urea in the liver. This would supply glucose for these tissues and explain why urea excretion may increase under such conditions. If the end-products are not recycled, it may decrease energy requirements, but it will increase the drain on body protein to provide nitrogen for glutamine synthesis.