Fractional synthetic rate lh j

CHO CHO+PRO CHO+PRO+LEU

FIGURE 13.4 Fractional synthetic rate (FSR) of mixed muscle protein in the recovery phase during trials in which carbohydrate only (CHO), carbohydrate with protein (CHO + PRO), and carbohydrate with protein and leucine (CHO + PRO + LEU) were consumed by men following a 45-min bout of resistance exercise. Co-ingestion of protein and leucine with carbohydrate stimulated muscle protein synthesis (and optimized whole-body protein balance) compared to the intake of carbohydrate only after the resistance exercise bout. Values are means ± SE. *, p < 0.05 significantly different from CHO. (From Koopman, R. et al., Am. J. Physiol. Endocrinol. Metab., 288, 645-653, 2005. Used with permission from the American Physiological Society.)

the rate at which the plasma BCAA pool is replenished through breakdown of whole-body proteins. The decline in plasma BCAA concentration during exercise will result in a further increase in the fTRP:BCAA ratio. Experimental studies in humans have confirmed that these events occur. The central fatigue hypothesis predicts that the increase in fTRP:BCAA ratio results in an increased fTRP transport across the blood-brain barrier because BCAA and fTRP compete for carrier-mediated entry into the central nervous system by the large neutral amino acid (LNAA) transporter.1819 Once taken up, the conversion of tryptophan to serotonin (5-hydroxy-tryptamine, or 5-HT) occurs and leads to a local increase of this neurotransmitter.19 Serotonin has been shown to depress motor neuron excitability, influence autonomic and endocrine function, and suppress appetite in both animal and human studies. Furthermore, serotonin plays a role in the onset of sleep and is a determinant of mood and aggression. Therefore, the increase in serotoninergic activity might subsequently lead to the development of central fatigue, forcing athletes to stop exercise or reduce the exercise intensity. Of course, the assumption that increased fTRP uptake leads to increased serotonin synthesis and activity of serotoninergic pathways (i.e., increased synaptic serotonin release) is a rather large leap of faith.

The central fatigue hypothesis also predicts that ingestion of BCAAs will raise the plasma BCAA concentration, and hence reduce transport of fTRP into the brain. Subsequent reduced formation of serotonin may alleviate sensations of fatigue (Figure 13.5b) and, in turn, improve endurance exercise performance.

CHO CHO+PRO CHO+PRO+LEU

FIGURE 13.4 Fractional synthetic rate (FSR) of mixed muscle protein in the recovery phase during trials in which carbohydrate only (CHO), carbohydrate with protein (CHO + PRO), and carbohydrate with protein and leucine (CHO + PRO + LEU) were consumed by men following a 45-min bout of resistance exercise. Co-ingestion of protein and leucine with carbohydrate stimulated muscle protein synthesis (and optimized whole-body protein balance) compared to the intake of carbohydrate only after the resistance exercise bout. Values are means ± SE. *, p < 0.05 significantly different from CHO. (From Koopman, R. et al., Am. J. Physiol. Endocrinol. Metab., 288, 645-653, 2005. Used with permission from the American Physiological Society.)

blood

"Central fatigue" hypothesis brain

FFA (Alb FFA FFA

fTrp fTrp BCAA

fTrp fTrp

Serotonin

blood fTrp, fatigue

Effect of BCAA ingestion brain fTrp BCAA -BCAA BCAA

BCAA fTrp ffa ^tr^

(Alb FFA FFA

Serotonin in

fatigue

FIGURE 13.5 Central fatigue hypothesis. (a) The central fatigue hypothesis proposes that during exercise free fatty acids (FFAs) are mobilized from adipose tissue and transported via the blood to the muscles to serve as fuel. Because the rate of mobilization is greater than the rate of uptake by the muscle, the circulating FFA concentration increases. Both FFA and the free amino acid tryptophan (fTRP) bind to albumin (ALB) and compete for the same binding sites. fTRP is displaced from binding to albumin by the increasing FFA concentration and, therefore, the fTRP concentration and the fTRP:BCAA ratio in the blood rise. Experimental studies in humans have confirmed that these events occur. The central fatigue hypothesis predicts that the increase in this ratio results in an increased fTRP transport across the blood-brain barrier because BCAAs and fTRP compete for carrier-mediated entry into the central nervous system by the large neutral amino acid (LNAA) transporter. Once taken up, the conversion of fTRP to serotonin (5-hydroxytryptamine, or 5-HT) occurs and leads to a local increase of this neurotransmitter. It has been well established that serotonin plays a role in the onset of sleep, and that it is a determinant of mood and aggression. It was therefore hypothesized that the increase in serotoninergic activity subsequently leads to central fatigue, forcing athletes to stop exercise or reduce exercise intensity. (b) The involvement of plasma fTRP and BCAAs in the central fatigue hypothesis also predicts that ingestion of BCAAs will raise the plasma BCAA concentration, and hence reduce transport of fTRP into the brain. Subsequent reduced formation of serotonin may alleviate sensations of fatigue, and hence improve endurance exercise performance.

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