Fuels for immune cells

Fuel for immune cells at rest and during proliferation. Enhances T-lymphocyte responses to infection. 

The long tail of myosin contains a high proportion of the amino acids leucine, isoleucine, aspartate and glutamate. These are released upon the degradation of myosin by intracellular proteases and peptidases and they provide nitrogen for the synthesis of glutamine. It is then stored in muscle and is a very important fuel for immune cells (Chapter 17). 

Glutamine Glutamine is the most frequently discussed nutraceutical in the cUnical literature as it is an essential fuel for immune and other proliferating cells and the plasma concentration decreases in a number of clinical conditions (Table 18.5). Provision of glutamine (or a dipeptide that contains glutamine), either enterally or parenteraUy, has... 

The catabolic state of sepsis (acute, generalized, febrile infection) is one of enhanced mobilization of fuels and amino acids to provide the energy and precursors required by cells of the immune system, host defense mechanisms, and wound heahng. The amino acids must provide the substrates for new protein synthesis and cell division. Glucose synthesis and release are enhanced to provide fuel for these cells, and the patient may become mildly hyperglycemic. 

Tumour cells also require glutamine as a fuel for energy generation and as a precursor for the synthesis of purine and pyrimidine nucleotides for DNA and RNA synthesis. The roles and importance of glutamine in tumour cells and possible competition between the cells for glutamine are discussed in Chapter 21. The pathway for the metabolism of glutamine is similar to that in the immune cells. 

The physiological usefulness of this method for identifying the fuels that are used and their rates of utilisation in different cells is discussed in other chapters (Chapter 3). For example, measurement of the activity of the enzymes hexokinase and glutaminase in immune cells showed, for the first time, that glucose and glutamine are the major fuels utilised by these cells. This finding has had clinical significance (Chapter 17). 

They stimulate response of the whole body (e.g. increase the rates of glycogenolysis in the liver and proteolysis in mnscle) to provide fuels for the immune cells (see below for details). 

Fuels and generation of ATP in immune cells consequences for a patient... 

The response of the body to an invasion by a pathogen involves not only the immnne system bnt other tissnes in which changes in metabolism are essential for a satisfactory response. These inclnde adipose tissne, mnscle and liver, all of which provide precnrsor molecnles (i.e. bnilding materials) for the synthesis of the macromolecnles required for proliferation (Table 17.5). In addition, they provide fuels, the oxidation of which generates ATP for the immune cells, particnlarly to snpport proliferation of the cells in the lymph nodes bnt also for the precnrsor cells in the bone marrow where proliferation increases to prodnce new immune and other cells (Table 17.6). 

FUELS AND GENERATION OF ATP IN IMMUNE CELLS CONSEQUENCES FOR A PATIENT... 

Fig. 42.3. Interorgan amino acid exchange after an overnight fast. After an overnight fast (the postabsorptive state), the utilization of amino acids for protein synthesis, for fuels, and for the synthesis of essential functional compounds continues. The free amino acid pool is supported largely by net degradation of skeletal muscle protein. Glutamine and alanine serve as amino group carriers from skeletal muscle to other tissues. Glutamine brings NH4 to the kidney for the excretion of protons and serves as a fuel for the kidney, gut, and cells of the immune system. Alanine transfers amino groups from skeletal muscle, the kidney, and the gut to the liver, where they are converted to urea for excretion. The brain continues to use amino acids for neurotransmitter synthesis.

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