Acta Physiol Scand 1990, 138, 259-262
Muscle carnitine metabolism during incremental dynamic exercise in humans K. S A H L I N Department of Clinical Physiology, Karolinska Institute, Huddinge University Hospital, Sweden
SAHLIN, K. 1990. Muscle carnitine metabolism during incremental dynamic exercise in humans. Acta Physiol Scand 138, 259-262. Received 5 October 1989, accepted 31 October 1989. ISSN 00014772. Department of Clinical Physiology, Karolinska Institute, Huddinge Hospital, Stockholm, Sweden. The changes in muscle content of carnitine and acetylcarnitine have been studied during incremental dynamic exercise. Six subjects exercised for 10 min on an ergometer at 40 and 75 yoof their maximal oxygen uptake ( VO,max) and to fatigue at 100%of VO, max (about 4 min). Muscle samples were taken from the quadriceps femoris muscle at rest and after exercise. Muscle content of free carnitine was (p+ SE) 15.9& 1.7 mmol kg d.wt (dry weight) at rest and remained unchanged after exercise at low intensity but decreased to 5.9fo.6 and 4.6fo.5 mmol kg-' d.wt after exercise at 75 and 100% of Vo, max respectively. Acetylcarnine content at rest was 6.9 I .9 mmol kg-' d.wt and increased during exercise in correspondence with the decrease in free carnitine. Muscle content of pyruvate and lactate was unchanged after exercise at 40% of Vo, max but increased at the higher intensities. The parallel increases in acetylcarnitine, pyruvate and lactate indicate that formation of acetylcarnitine is augmented when the availability of glycolytic three-carbon metabolites is high and is consistent with the idea that acetylcarnitine provides a sink for pyruvate and acetyl CoA. This could be of importance for the maintenance of an adequate level of CoA and thus function of the tricarboxylic acid cycle.
-'
Key mords ; acetylcarnitine, carnitine, lactate, pyruvate.
Carnitine is a co-factor for the transport of longchain fatty acids (FA) across the inner mitochondrial membrane and is thus essential for the mitochondria1 P-oxidation of fatty acids. A relation has been observed between the muscle concentration of carnitine and the in-vitro capacity for F A oxidation (Cederblad et al. 1976). However, carnitine supplementation to humans, resulting in a doubling of plasma carnitine, had no effect on substrate utilization during exercise (Soop et al. 1988) and indicates that the carnitine concentration was not limiting for the oxidation of FA under these conditions. I t has been shown in humans that intensive exercise results in a transformation of a large Correspondence : Dr Kent Sahlin, Department of Clinical Physiology, Karolinska Institute, Huddinge University Hospital, S-141 86 Huddinge, Sweden.
part of the muscle carnitine to acetylcarnitine (Harris et al. 1987, Hiatt et al. 1989). However, during prolonged submaximal exercise the proportion of the carnitine pool present as free carnitine has been shown either to be constant (Lennon et al. 1983, Hiatt et al. 1989) or to decrease (Carlin et al. 1986). Unfortunately, neither pyruvate nor lactate was measured in these studies. T h e aim of the present study was to investigate the influence of exercise intensity on the carnitine and acetyl carnitine content in human muscle and to elucidate the relation to pyruvate and lactate accumulation.
M A T E R I A L S A N D METHODS Subjects. Six healthy men participated in the srudy. Their mean (range) age, height, weight and maximal
259
260
K. Sahlin
oxygen uptake (Vo, max) were respectively 27 (22-31) years, 183 (174-190) cm, 78 (71-85) kg and 4.34 (3.92-4.84) 1 min-' or 55.7 (48-63.4) ml min-' kg-'. The subjects were informed about the possible risks of the study before giving their voluntary consent. T h e experimental protocol was approved by the Ethics Committee of the Karolinska Institute at Huddinge University Hospital. Experimental. Subjects performed incremental bicycle exercise at intensities corresponding to 40 and 75*b of P'o, max for 10 min each, and at rooo/; Vo, max to fatigue (4.11 0 . 4 min). The workloads were rzz+4 W ( ~ O OVo,max),232+8 /~ W(75o/b Vo,max) and 309+10 W ( I O O O ~ Vo, max). Muscle samples were taken from the quadriceps femoris muscle with the needle biopsy technique at rest and after exercise at each workload. Subjects interrupted the exercise for about 30 s, during which the muscle biopsies were taken, before continuing the exercise at a higher workload. .4nalytical methods. T h e frozen muscle samples (stored in liquid N,) were freeze-dried, dissected free from visible connective tissue and blood, and powdered. The powder was extracted with perchloric acid " (PCA 0.jhi), which was neutralized with KIICO, ( 2 . 2 M) and thereafter analysed with enzymatic fluorometric methods, for acetylcarnitine (Pearson 40%100% 0 10 20 25 et al. 1974), lactate and pyruvate. Free carnitine was (rnln) determined by the method described by Marquis & Fritz (1964). Fig. I. Muscle content of lactate and pyruvate at rest Statistical method. For statistical evaluation, a one- and during exercise. " P < 0.05 uus rest. way analysis of variance (ANOVA) with a repeatedmeasure design was employed. When the ANOVA 201 resulted in a significant F Jralue (P< 0.05), the statistical significance of the difference between means was determined by the Newman-Keul test. Values are presented as means SE.
I
s
RESULTS Muscle lactate remained unchanged after exercise at 40% of Yo, max (P> 0.05) but increased 18-fold and jo-fold after exercise at 75 and ~ o o q bof Vo, max respectively (Fig. I ) . Muscle pyruvate was not significantly changed (P > 0.0j ) after exercise at 40% but increased a t the higher intensities to a value about fourfold higher than the value at rest. Muscle content of carnitine was I 5.9 f I .7 mmol kg-' d.wt at rest, did not change after exercise at low intensity but decreased to about f of the initial value after exercise at 7500 and 100% of Yo2 max (Fig. 2). Acetylcarnitine content at rest was 6.9 & 1.9 mmol kg-' d.wt and remained unchanged after low-intensity exercise but increased at the higher intensities
-E
CI
$ 0
0
J I
40%
0
I!
75%
10
11 100%I
20
25
(rnln)
Fig. 2 . Muscle content of carnitine ( 0 ) and acetylcarnitine (0) at rest and during exercise. " P < 0.05 t's rest.
reaching 18.1 1.0mmol kg-' d.wt at fatigue (Fig. 2). The increase in acetylcarnitine was similar to the decrease in carnitine and the sum (acetylcarnitine carnitine) was not changed by
+
Formation of acetylcarnitine
exercise (22.9+ 1 . 1 mmol kg-' d.wt at rest and 22.7 f 1.3 at fatigue).
261
acetylcarnitine may prevent a depletion of CoA. This is essential for the function of the tricarboxylic acid. Pyruvate dehydrogenase (PDH) is the fluxgenerating step for pyruvate oxidation and is DISCUSSION present in two interconvertible forms. TransThe data from the present study show that major formation of the inactive form of P D H to the changes occur within the carnitine pool in human active form is stimulated by Ca2+,thus providing skeletal muscle during intensive exercise. Thus, a link between muscle contraction and oxidative acetylcarnitine increased about threefold and metabolism. Transformation of the active form to free carnitine decreased correspondingly to about the inactive form is enhanced by increases in 30 yoof the initial value. The present data are in ATP/ADP, acetyl CoA/CoA, and mitochondrial agreement with the results reported by Harris NADH/NAD while pyruvate inhibits the transet al. (1987) and Hiatt et al. (1989) where free formation (for references see Hansford (1980). carnitine after intensive bicycle exercise An increased availability of fat has been (8~~90% of Vo, max) decreased by about shown to induce an increased fat oxidation and a 5 ~ 7 0 % .The effect of prolonged submaximal decreased carbohydrate (CHO) oxidation. This exercise on carnitine metabolism has previously was originally described to occur in cardiac been studied (Lennon et' al. 1983, Carlin et al. muscle (Randle et al. 1963) but has also been 1986, Hiatt et al. 1989) but the results are shown in skeletal muscle (Rennie et al. 1976, divergent. Unfortunately neither muscle Costill et al. 1977). Randle et al. (1963) suggested pyruvate nor lactate was measured in these that the decreased rate of CHO oxidation was studies, and a comparison with the present data caused by an inhibition of P D H and phosphofructokinase through increases in acetyl is therefore difficult. An important finding in the present study was CoA and citrate respectively (the Randle hythat an exercise-induced increase in pothesis). acetylcarnitine occurred only when muscle Exercise at 75 and 100% VO, max results in pyruvate and lactate were elevated. Thus, increased mitochondrial NADH levels (Sahlin exercise at low intensity induced an increase in et al. 1987) and probably in an increased acetyl neither acetylcarnitine nor in pyruvate and CoA/CoA ratio as indicated by the increase in lactate. These data are consistent with the idea acetylcarnitine/carnitine ratio observed in the (Harris et a/. 1987) that acetylcarnitine is formed present study. These metabolic changes would during conditions of excess pyruvate and lactate favour a transformation of the active form of and therefore acetylcarnitine may function as a PDH to the inactive form. However, it is well sink for pyruvate, or rather acetyl CoA. This known that during intensive exercise the reshypothesis is supported by recent findings piratory exchange ratio is increased, and thus the (Sahlin et al., unpublished data) in myo- oxidation of pyruvate is increased both in phosphorylase-deficient patients (McArdle's absolute terms and in proportion to the total disease) where acetylcarnitine at rest was very substrate oxidation. The presumed inhibitory low (corresponding to about 17% of the value effects of acetyl CoA and NADH on PDH are observed in the present study in healthy subjects therefore adequately overcome, possibly due to at rest). Furthermore, the concentration of increases in the mitochondrial concentration of acetylcarnitine in muscle remained low during pyruvate, ADP and Ca2+.I t is possible that the intensive exercise in the McArdle patients (when Randle hypothesis is valid for skeletal muscle muscle lactate and pyruvate also remained low), only during exercise at low intensity. whereas a pronounced increase occurred in The decrease in free carnitine during intensive healthy subjects (Fig. I). Since acetylcarnitine/ exercise may limit the transport of FA into the carnitine can function as a buffer of the acetyl mitochondria and could therefore provide a CoA/CoA ratio (for references see Bieber 1988) mechanism whereby an increased availability of it is likely that an increase in acetylcarnitine also pyruvate and lactate slows down the oxidation of corresponds to an increased acetyl CoA/CoA fat. Since oxidation of CHO requires less 0, for ratio. Since the total carnitine level is much a given amount of produced ATP than oxidation larger than the total CoA level, formation of of fat, a change from fat to CHO oxidation could
262
K. Sahlin
LENNON,D.L.F., STRATMAN, F.W., SHRAGO, E., NAGLE, F.J., MADDEN, M., HANSON,P. & CARTER, -4.L. 1983. Effects of acute moderate intensity exercise on carnitine metabolism in men and The present study was supported bl- grants from the women. 3 -4ppl Physiol 55, 489-495. Karolinska Institute and the Swedish Medical ReLOWRY, O.H. & PASSONNEAU, J.V. 1972. A Flexible search Council (8671). Sjlsrem of Enzymatic Analysis. New York, Academic Press. REFERENCES MARQUIS, N.R. & FRITZ, I.B. 1964.Enzymological determination of free carnitine concentrations in rat BIEBER, L.L. 1988.Carnitine. .4nn Rez: Biochern 57, tissues. 3 Lipid Res 5, 184-187. 261-283. D.J., TUBBS, P.K. & CHASE,F.A. 1974. CARLIN, J . I . , REDDAS,W.G., SANJAK, hf. & HODACH. PEARSON, Carnitine and acylcarnitine. In : H.V. Bergmeyer R. 1986.Carnitine metabolism during prolonged (ed.) Methods ofEnzymatic Analysis, pp. 1758-1771. cvrrcise and recover!- in humans. .4m 3 Ph.ysiol 61, London, Academic Press. lZ7j-1278. P.B., HALES,C.N. & CEDERMAD, G., BYLUND, .4,-C., HOLM, J. 8i RANDLE, P.J., GARLAND, NEWSHOLME, E.A. 1963. T h e glucose fatty-acid SCHERSTEN, T. 1976. Carnitine concentration in cycle: Its role in insulin sensitivity and the metabolic relation to enzyme activities and substrate disturbances ofdiabetes mellitus. Lancet I, 785-789. utilization in human skeletal muscles. S c u m 1 3 Clin RENNIE,M.J.,WINDER,W.N. &HOLLOSZY, J.O. 1976. Lub Inrest 36, 547-552. COSTII.L, D.L., COYLE, E., DALSKY, G., EVANS, W., h sparing effect of increased plasma fatty acids on muscle and liver glycogen content in the exercising FINK,W. & HOOPES, D. 1977.Effects of elevated rat. Biorhern f 156, 647455. plasma FF.4 and insulin on muscle glycogen usage SAHLIN, K., KATZ,A. & HENRIKSSON, J. 1987.Redox during exercise. 'j.4ppl Physiol 43, 695-699. state and lactate accumulation in human skeletal HANSFORD, R.G. 1980. Control of mitochondria1 muscle during dynamic exercise. Biochem 3 245, substrate oxidation. Curr Top Bioenerg 10,217-278. HARRIS, R.C., FOSTER, C.V.L. & HULTMAN, E. 1987. 55 '-556. G., Acetylcarnitine formation during intense muscular SOOP, M., BJORKMAN,O., CEDERBLAD, HAGENFELDT, I,. & WAHREN, J. 1988.Influence of contraction in humans. 3.4ppl Physiol63,440-..~2. carnitine supplementation on muscle substrate and HIATT,W.R., REGENSTEINER, J.G., WOLFEL, E.E. & carnitine metabolism during exercise. J A p p l Ph.ysio1 BRASS,E.P. 1989. Carnitine and acetylcarnitine metabolism during exercise in humans. 3 Clin 643 2394-2399, Invest 84, 1167-1173.
be advantageous during conditions of 0, deficiency.
Muscle carnitine metabolism during incremental dynamic exercise in humans K. S A H L I N Department of Clinical Physiology, Karolinska Institute, Huddinge University Hospital, Sweden
SAHLIN, K. 1990. Muscle carnitine metabolism during incremental dynamic exercise in humans. Acta Physiol Scand 138, 259-262. Received 5 October 1989, accepted 31 October 1989. ISSN 00014772. Department of Clinical Physiology, Karolinska Institute, Huddinge Hospital, Stockholm, Sweden. The changes in muscle content of carnitine and acetylcarnitine have been studied during incremental dynamic exercise. Six subjects exercised for 10 min on an ergometer at 40 and 75 yoof their maximal oxygen uptake ( VO,max) and to fatigue at 100%of VO, max (about 4 min). Muscle samples were taken from the quadriceps femoris muscle at rest and after exercise. Muscle content of free carnitine was (p+ SE) 15.9& 1.7 mmol kg d.wt (dry weight) at rest and remained unchanged after exercise at low intensity but decreased to 5.9fo.6 and 4.6fo.5 mmol kg-' d.wt after exercise at 75 and 100% of Vo, max respectively. Acetylcarnine content at rest was 6.9 I .9 mmol kg-' d.wt and increased during exercise in correspondence with the decrease in free carnitine. Muscle content of pyruvate and lactate was unchanged after exercise at 40% of Vo, max but increased at the higher intensities. The parallel increases in acetylcarnitine, pyruvate and lactate indicate that formation of acetylcarnitine is augmented when the availability of glycolytic three-carbon metabolites is high and is consistent with the idea that acetylcarnitine provides a sink for pyruvate and acetyl CoA. This could be of importance for the maintenance of an adequate level of CoA and thus function of the tricarboxylic acid cycle.
-'
Key mords ; acetylcarnitine, carnitine, lactate, pyruvate.
Carnitine is a co-factor for the transport of longchain fatty acids (FA) across the inner mitochondrial membrane and is thus essential for the mitochondria1 P-oxidation of fatty acids. A relation has been observed between the muscle concentration of carnitine and the in-vitro capacity for F A oxidation (Cederblad et al. 1976). However, carnitine supplementation to humans, resulting in a doubling of plasma carnitine, had no effect on substrate utilization during exercise (Soop et al. 1988) and indicates that the carnitine concentration was not limiting for the oxidation of FA under these conditions. I t has been shown in humans that intensive exercise results in a transformation of a large Correspondence : Dr Kent Sahlin, Department of Clinical Physiology, Karolinska Institute, Huddinge University Hospital, S-141 86 Huddinge, Sweden.
part of the muscle carnitine to acetylcarnitine (Harris et al. 1987, Hiatt et al. 1989). However, during prolonged submaximal exercise the proportion of the carnitine pool present as free carnitine has been shown either to be constant (Lennon et al. 1983, Hiatt et al. 1989) or to decrease (Carlin et al. 1986). Unfortunately, neither pyruvate nor lactate was measured in these studies. T h e aim of the present study was to investigate the influence of exercise intensity on the carnitine and acetyl carnitine content in human muscle and to elucidate the relation to pyruvate and lactate accumulation.
M A T E R I A L S A N D METHODS Subjects. Six healthy men participated in the srudy. Their mean (range) age, height, weight and maximal
259
260
K. Sahlin
oxygen uptake (Vo, max) were respectively 27 (22-31) years, 183 (174-190) cm, 78 (71-85) kg and 4.34 (3.92-4.84) 1 min-' or 55.7 (48-63.4) ml min-' kg-'. The subjects were informed about the possible risks of the study before giving their voluntary consent. T h e experimental protocol was approved by the Ethics Committee of the Karolinska Institute at Huddinge University Hospital. Experimental. Subjects performed incremental bicycle exercise at intensities corresponding to 40 and 75*b of P'o, max for 10 min each, and at rooo/; Vo, max to fatigue (4.11 0 . 4 min). The workloads were rzz+4 W ( ~ O OVo,max),232+8 /~ W(75o/b Vo,max) and 309+10 W ( I O O O ~ Vo, max). Muscle samples were taken from the quadriceps femoris muscle with the needle biopsy technique at rest and after exercise at each workload. Subjects interrupted the exercise for about 30 s, during which the muscle biopsies were taken, before continuing the exercise at a higher workload. .4nalytical methods. T h e frozen muscle samples (stored in liquid N,) were freeze-dried, dissected free from visible connective tissue and blood, and powdered. The powder was extracted with perchloric acid " (PCA 0.jhi), which was neutralized with KIICO, ( 2 . 2 M) and thereafter analysed with enzymatic fluorometric methods, for acetylcarnitine (Pearson 40%100% 0 10 20 25 et al. 1974), lactate and pyruvate. Free carnitine was (rnln) determined by the method described by Marquis & Fritz (1964). Fig. I. Muscle content of lactate and pyruvate at rest Statistical method. For statistical evaluation, a one- and during exercise. " P < 0.05 uus rest. way analysis of variance (ANOVA) with a repeatedmeasure design was employed. When the ANOVA 201 resulted in a significant F Jralue (P< 0.05), the statistical significance of the difference between means was determined by the Newman-Keul test. Values are presented as means SE.
I
s
RESULTS Muscle lactate remained unchanged after exercise at 40% of Yo, max (P> 0.05) but increased 18-fold and jo-fold after exercise at 75 and ~ o o q bof Vo, max respectively (Fig. I ) . Muscle pyruvate was not significantly changed (P > 0.0j ) after exercise at 40% but increased a t the higher intensities to a value about fourfold higher than the value at rest. Muscle content of carnitine was I 5.9 f I .7 mmol kg-' d.wt at rest, did not change after exercise at low intensity but decreased to about f of the initial value after exercise at 7500 and 100% of Yo2 max (Fig. 2). Acetylcarnitine content at rest was 6.9 & 1.9 mmol kg-' d.wt and remained unchanged after low-intensity exercise but increased at the higher intensities
-E
CI
$ 0
0
J I
40%
0
I!
75%
10
11 100%I
20
25
(rnln)
Fig. 2 . Muscle content of carnitine ( 0 ) and acetylcarnitine (0) at rest and during exercise. " P < 0.05 t's rest.
reaching 18.1 1.0mmol kg-' d.wt at fatigue (Fig. 2). The increase in acetylcarnitine was similar to the decrease in carnitine and the sum (acetylcarnitine carnitine) was not changed by
+
Formation of acetylcarnitine
exercise (22.9+ 1 . 1 mmol kg-' d.wt at rest and 22.7 f 1.3 at fatigue).
261
acetylcarnitine may prevent a depletion of CoA. This is essential for the function of the tricarboxylic acid. Pyruvate dehydrogenase (PDH) is the fluxgenerating step for pyruvate oxidation and is DISCUSSION present in two interconvertible forms. TransThe data from the present study show that major formation of the inactive form of P D H to the changes occur within the carnitine pool in human active form is stimulated by Ca2+,thus providing skeletal muscle during intensive exercise. Thus, a link between muscle contraction and oxidative acetylcarnitine increased about threefold and metabolism. Transformation of the active form to free carnitine decreased correspondingly to about the inactive form is enhanced by increases in 30 yoof the initial value. The present data are in ATP/ADP, acetyl CoA/CoA, and mitochondrial agreement with the results reported by Harris NADH/NAD while pyruvate inhibits the transet al. (1987) and Hiatt et al. (1989) where free formation (for references see Hansford (1980). carnitine after intensive bicycle exercise An increased availability of fat has been (8~~90% of Vo, max) decreased by about shown to induce an increased fat oxidation and a 5 ~ 7 0 % .The effect of prolonged submaximal decreased carbohydrate (CHO) oxidation. This exercise on carnitine metabolism has previously was originally described to occur in cardiac been studied (Lennon et' al. 1983, Carlin et al. muscle (Randle et al. 1963) but has also been 1986, Hiatt et al. 1989) but the results are shown in skeletal muscle (Rennie et al. 1976, divergent. Unfortunately neither muscle Costill et al. 1977). Randle et al. (1963) suggested pyruvate nor lactate was measured in these that the decreased rate of CHO oxidation was studies, and a comparison with the present data caused by an inhibition of P D H and phosphofructokinase through increases in acetyl is therefore difficult. An important finding in the present study was CoA and citrate respectively (the Randle hythat an exercise-induced increase in pothesis). acetylcarnitine occurred only when muscle Exercise at 75 and 100% VO, max results in pyruvate and lactate were elevated. Thus, increased mitochondrial NADH levels (Sahlin exercise at low intensity induced an increase in et al. 1987) and probably in an increased acetyl neither acetylcarnitine nor in pyruvate and CoA/CoA ratio as indicated by the increase in lactate. These data are consistent with the idea acetylcarnitine/carnitine ratio observed in the (Harris et a/. 1987) that acetylcarnitine is formed present study. These metabolic changes would during conditions of excess pyruvate and lactate favour a transformation of the active form of and therefore acetylcarnitine may function as a PDH to the inactive form. However, it is well sink for pyruvate, or rather acetyl CoA. This known that during intensive exercise the reshypothesis is supported by recent findings piratory exchange ratio is increased, and thus the (Sahlin et al., unpublished data) in myo- oxidation of pyruvate is increased both in phosphorylase-deficient patients (McArdle's absolute terms and in proportion to the total disease) where acetylcarnitine at rest was very substrate oxidation. The presumed inhibitory low (corresponding to about 17% of the value effects of acetyl CoA and NADH on PDH are observed in the present study in healthy subjects therefore adequately overcome, possibly due to at rest). Furthermore, the concentration of increases in the mitochondrial concentration of acetylcarnitine in muscle remained low during pyruvate, ADP and Ca2+.I t is possible that the intensive exercise in the McArdle patients (when Randle hypothesis is valid for skeletal muscle muscle lactate and pyruvate also remained low), only during exercise at low intensity. whereas a pronounced increase occurred in The decrease in free carnitine during intensive healthy subjects (Fig. I). Since acetylcarnitine/ exercise may limit the transport of FA into the carnitine can function as a buffer of the acetyl mitochondria and could therefore provide a CoA/CoA ratio (for references see Bieber 1988) mechanism whereby an increased availability of it is likely that an increase in acetylcarnitine also pyruvate and lactate slows down the oxidation of corresponds to an increased acetyl CoA/CoA fat. Since oxidation of CHO requires less 0, for ratio. Since the total carnitine level is much a given amount of produced ATP than oxidation larger than the total CoA level, formation of of fat, a change from fat to CHO oxidation could
262
K. Sahlin
LENNON,D.L.F., STRATMAN, F.W., SHRAGO, E., NAGLE, F.J., MADDEN, M., HANSON,P. & CARTER, -4.L. 1983. Effects of acute moderate intensity exercise on carnitine metabolism in men and The present study was supported bl- grants from the women. 3 -4ppl Physiol 55, 489-495. Karolinska Institute and the Swedish Medical ReLOWRY, O.H. & PASSONNEAU, J.V. 1972. A Flexible search Council (8671). Sjlsrem of Enzymatic Analysis. New York, Academic Press. REFERENCES MARQUIS, N.R. & FRITZ, I.B. 1964.Enzymological determination of free carnitine concentrations in rat BIEBER, L.L. 1988.Carnitine. .4nn Rez: Biochern 57, tissues. 3 Lipid Res 5, 184-187. 261-283. D.J., TUBBS, P.K. & CHASE,F.A. 1974. CARLIN, J . I . , REDDAS,W.G., SANJAK, hf. & HODACH. PEARSON, Carnitine and acylcarnitine. In : H.V. Bergmeyer R. 1986.Carnitine metabolism during prolonged (ed.) Methods ofEnzymatic Analysis, pp. 1758-1771. cvrrcise and recover!- in humans. .4m 3 Ph.ysiol 61, London, Academic Press. lZ7j-1278. P.B., HALES,C.N. & CEDERMAD, G., BYLUND, .4,-C., HOLM, J. 8i RANDLE, P.J., GARLAND, NEWSHOLME, E.A. 1963. T h e glucose fatty-acid SCHERSTEN, T. 1976. Carnitine concentration in cycle: Its role in insulin sensitivity and the metabolic relation to enzyme activities and substrate disturbances ofdiabetes mellitus. Lancet I, 785-789. utilization in human skeletal muscles. S c u m 1 3 Clin RENNIE,M.J.,WINDER,W.N. &HOLLOSZY, J.O. 1976. Lub Inrest 36, 547-552. COSTII.L, D.L., COYLE, E., DALSKY, G., EVANS, W., h sparing effect of increased plasma fatty acids on muscle and liver glycogen content in the exercising FINK,W. & HOOPES, D. 1977.Effects of elevated rat. Biorhern f 156, 647455. plasma FF.4 and insulin on muscle glycogen usage SAHLIN, K., KATZ,A. & HENRIKSSON, J. 1987.Redox during exercise. 'j.4ppl Physiol 43, 695-699. state and lactate accumulation in human skeletal HANSFORD, R.G. 1980. Control of mitochondria1 muscle during dynamic exercise. Biochem 3 245, substrate oxidation. Curr Top Bioenerg 10,217-278. HARRIS, R.C., FOSTER, C.V.L. & HULTMAN, E. 1987. 55 '-556. G., Acetylcarnitine formation during intense muscular SOOP, M., BJORKMAN,O., CEDERBLAD, HAGENFELDT, I,. & WAHREN, J. 1988.Influence of contraction in humans. 3.4ppl Physiol63,440-..~2. carnitine supplementation on muscle substrate and HIATT,W.R., REGENSTEINER, J.G., WOLFEL, E.E. & carnitine metabolism during exercise. J A p p l Ph.ysio1 BRASS,E.P. 1989. Carnitine and acetylcarnitine metabolism during exercise in humans. 3 Clin 643 2394-2399, Invest 84, 1167-1173.
be advantageous during conditions of 0, deficiency.
