Plasma and Muscle Glutamine Levels in Catabolic Stress

One of the early responses to stress that occurs in skeletal muscle is the increased rate of export of glutamine from the intracellular free amino acid pool. This lowers the intracellular glutamine concentration, leading to protein breakdown and de novo synthesis of glutamine from other amino acids. Glutamine synthetase in skeletal muscle is up-regulated by glucocorticoids (Max et al., 1988) and by TNF-a (Chakrabarti, 1998), and glucocorticoids increase glutamine efflux from skeletal muscle (Muhlbacher et al., 1984; Parry-Billings et al., 1990b). Thus, there appears to be an attempt in stress states to increase the supply of glutamine from muscle to the rest of the body. Nevertheless, glucocorticoid treatment decreases skeletal muscle and plasma glutamine concentrations (Muhlbacher et al., 1984; Parry-Billings et al., 1990b), suggesting that the demand for glutamine exceeds the supply.

Animal studies indicate that intramuscular and plasma glutamine concentrations are decreased in catabolic-stress situations, such as in sepsis and cancer cachexia and following burn injury and surgery (Table 6.3). In humans, plasma glutamine levels are lowered (by up to 50%) by sepsis, major injury and burns and following surgery (see Table 6.4). A recent study reported that low plasma glutamine concentration (< 0.42 mM) at admission to intensive care was associated with higher severity of illness and higher mortality (Oudemans-van Straaten et al., 2001). In humans, the skeletal-muscle glutamine concentration is lowered by more than 50% in catabolic stress (see Table 6.4). These observations indicate that a significant depletion of the skeletal-muscle glutamine pool is characteristic of catabolic stress. The lowered plasma glutamine concentrations that occur are most probably the result of demand for glutamine (by the liver, kidney, gut and immune system) exceeding the supply, and it is proposed that glutamine be considered a conditionally essential amino acid during cata-bolic stress (Lacey and Wilmore, 1990; Wilmore and Shabert, 1998). It has been suggested that the lowered plasma glutamine availability contributes, at least in part, to the immunosuppression that accompanies such situations (Newsholme and Calder, 1997). Because of the apparent immunostimulatory actions of glutamine described above, it seems sensible to provide glutamine for patients following surgery, radiation treatment or bone-marrow transplantation or suffering from injury, sepsis or burns.

Table 6.3. Effect of catabolic stress on plasma and muscle glutamine concentrations in animals. Values separated by ^ indicate the concentrations observed in control and stressed animals, respectively.

Plasma glutamine

Skeletal-muscle

Model

(mM)

glutamine (mM)

Reference

Rat injury

ND

9.9 ^ 5.9

Albina et al. (1987)

Rat sepsis

1.1 ^ 0.8

3.8 ^ 1.5

Parry-Billings et al. (1989)

Rat cancer cachexia

1.0 ^ 0.8

5.1 ^ 2.3

Parry-Billings et al. (1991)

Rat burn injury

0.7 ^ 0.5

4.1 ^ 2.7

Ardawi (1988b)

Dog burn injury

0.7 ^ 0.5

7.6 ^ 6.0

Stinnett et al. (1982)

Pig post-surgery

0.3 ^ 0.2

ND

Deutz et al. (1992)

ND, not determined.

ND, not determined.

Table 6.4. Effect of stress on plasma and muscle glutamine concentrations in humans. Values separated by ^ indicate the concentrations observed in healthy controls and in patients with the indicated catabolic stress, respectively.

Plasma glutamine

Skeletal-muscle

Catabolic stress

(mM)

glutamine (mM)

Reference

Trauma/burns

0.60 ^ 0.70

20.0 ^ 10.0

Furst et al. (1979)

Injury

0.78 ^ 0.51

20.5 ^ 9.1

Askanazi et al. (1980)

Sepsis

0.53 ^ 0.37

19.3 ^ 6.7

Roth et al. (1982)

Sepsis

0.78 ^ 0.62

20.5 ^ 9.5

Askanazi et al. (1980)

Sepsis

0.38 ^ 0.30

22.0 ^ 4.0

Milewski et al. (1982)

Burns

0.62 ^ 0.30

ND

Parry-Billings et al. (1990a)

Burns

0.83 ^ 0.50

ND

Stinnett et al. (1982)

Surgery

0.65 ^ 0.48

ND

Parry-Billings et al. (1992a)

Surgery

0.46 ^ 0.36

ND

Lund et al. (1986)

Surgery

0.69 ^ 0.59

18.8 ^ 9.5

Askanazi et al. (1978)

Surgery

0.60 ^ 0.70

20.0 ^ 10.0

Askanazi et al. (1980)

Surgery

0.62 ^ 0.48

ND

Powell et al. (1994)

ND, not determined.

There are also reports of decreased plasma glutamine concentrations after endurance exercise (Parry-Billings et al., 1992b; Rohde et al., 1996b; Castell et al., 1997) and athletic training (Keast et al., 1995; Hack et al., 1997) and in the overtrained athlete (Parry-Billings et al., 1992b).

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