Carbohydrate supplementation
attenuates IMP accumulation
in human muscle during prolonged exercise
MARK
K. SPENCER,
ZHEN YAN, AND ABRAM
KATZ
Department
of Kinesiology, University of Illinois, Urbana, Illinois 61801
SPENCER,
MARK
K., ZHEN YAN, AND ABRAM
KATZ.
Carbohydrate supplementation
attenuates IMP accumulation
in human muscle during prolonged exercise. Am. J. Physiol. 261 (Cell
Physiol. 30): C71-C76,
1991. -The
effect of carbohydrate
(CHO) ingestion on metabolic responses to exercise has been
investigated.
Subjects cycled at -70% of maximal oxygen uptake to fatigue [135 t 17 (-I-SE) min] on the first occasion
(control, CON) and at the same work load and duration on the
second occasion but with addition of ingestion of CHO during
the exercise. Biopsies were taken from the quadriceps femoris
muscle before and after exercise. The sum of the hexose monophosphates (HMP), as well as lactate and alanine, in muscle
was higher after CHO exercise (P 5 0.05, P 5 0.05, and P 5
0.01, respectively).
Acetylcarnitine
increased during exercise
but was not significantly
different between treatments
after
exercise (CON, 6.6 t 1.7; CHO, 10.0 t 1.2 mmol/kg dry wt; P
= NS). The sum of the tricarboxylic
acid cycle intermediates
(TCAI; citrate + malate + fumarate)
was increased during
exercise and was higher after CHO exercise (2.34 t 0.32 vs.
1.68 t 0.17 mmol/kg dry wt; P 5 0.05). IMP was ~0.1 mmol/
kg dry wt at rest and increased to 0.77 t 0.26 (CON) and 0.29
t 0.11 mmol/kg dry wt (CHO) (P 5 0.05) during exercise. It
was recently found that during prolonged
exercise there is
initially a rapid and large expansion of TCAI and glycogenolytic
intermediates
in human muscle followed by a continuous
decline in TCAI and glycogenolytic
intermediates
[K. Sahlin, A.
Katz, and S. Broberg. Am. J. Physiol. 259 (Cell Physiol. 28):
C834-C841,
19901. Therefore,
the present data indicate that
administration
of exogenous CHO attenuates reversal of TCAI.
Presumably
this is achieved by increasing the availability
of
HMP for glycolysis. These effects of CHO supplementation
are
achieved at lower levels of physiological
stress, as evidenced by
an attenuated IMP accumulation
during the CHO experiment.
glycogenolysis; hexose phosphates; adenine nucleotides; acetylcarnitine; tricarboxylic
acid cycle intermediates;
amino acids;
fatigue; lactate
IS WELL
KNOWN
that consumption of a high carbohydrate diet before exercise results in an increased capacity to perform submaximal exercise (10). Also, physical work capacity is closely associated with the glycogen
content in muscle at exercise intensities of 6080% of
maximal oxygen uptake (Vozmax) (6, 14). However, the
link between carbohydrate (CHO) availability and physical work capacity, i.e., muscle fatigue, is poorly understood. It has recently been demonstrated that during
prolonged exercise there is initially a rapid and large
expansion of the tricarboxylic acid cycle intermediates
(TCAI), as well as large increases in glycogenolytic intermediates in human muscle. However, as the exercise
IT
0363-6143/91
$1.50
Copyright
progressed and the muscle glycogen content decreased,
the contents of TCAI and glycogenolytic intermediates
decreased continuously and IMP started to accumulate,
and by the point of fatigue IMP had increased GO-fold
(24). Because it is considered that expansion of the TCAI
is important to attain an optimal aerobic energy transduction (19), it was suggested that depletion of CHO
may impair aerobic energy production by reducing the
availability of TCAI in the muscle (24). If this hypothesis
is correct, one would expect that provision of exogenous
CHO would attenuate the decrease in TCAI and glycogenolytic intermediates, as well as the increase in IMP
during the latter stage of exercise. As a consequence,
exercise capacity should be enhanced. Consistent with
this hypothesis is the finding that administration of
exogenous CHO during exercise results in an increase in
exercise capacity (11, 12). Whether the enhanced exercise capacity is associated with higher levels of TCAI
and glycogenolytic intermediates and lower contents of
IMP in the muscle is not known.
The purpose of this study was to determine the role of
CHO availability in the development of muscle fatigue
during contraction. Specifically, the effects of CHO
ingestion during exercise on the contents of TCAI, glycogenolytic intermediates, and IMP in human skeletal
muscle have been examined.
MATERIALS
AND
METHODS
Subjects. Nine healthy endurance-trained cyclists (8
men, 1 woman), whose mean age (range), height, weight,
and VOW maxwere, respectively, 28 yr (19-47), 175 cm
(164-185), 74 kg (59-85), and 4.67 l/min (3.33-5.29),
participated in the study. The subjects were informed of
the possible risks involved before giving voluntary consent. The experimental protocol was approved by the
University of Illinois Institutional Review Board.
Experimental design. Vozmax was determined -1 wk
before the experiment by graded cycling on an electrically
braked cycle ergometer (Bosch ERG-551) in the upright
position at 90 revolutions per minute (rpm) to fatigue.
The peak VO, was considered to be Voz max.
Subjects were instructed not to exercise for 2 days
before each experiment and reported to the laboratory
after an overnight fast. After the subject assumed the
supine position, a plastic catheter was placed in an
antecubital vein, and incisions were made over the lateral
aspect of the quadriceps femoris muscle of both thighs
at -35% of the distance from the superior margin of the
0 1991 the American
Physiological
Society
C71
C72
CARBOHYDRATE
AND
patella to the anterior iliac spine. Subjects then rested
for -20 min, during which expired gases were collected.
Thereafter, the first blood sample and muscle biopsy (5)
were obtained. Subjects then cycled (90 rpm) for 2 min
at a power output calculated to correspond
to 50% of
vo 2 max (132 t 7 W); thereafter,
the work load was
immediately increased to one calculated to correspond to
70% Of V02max (204 t 10 W). The subjects cycled at this
work load to fatigue (point at which 50 rpm could not be
maintained). After the first 15 min of exercise, and every
15 min thereafter,
the subjects ingested cold orangeflavored and artificially
sweetened
(aspartame)
water
(3.6 ml/kg body wt). This was the control condition
(CON). Respiratory
exchange and heart rate were determined, and blood samples were drawn throughout
exercise. A second biopsy was obtained at fatigue. After the
second biopsy, the subjects resumed cycling at the higher
work load to fatigue. The subjects were not given any
drink during the second ride.
Approximately
1 wk later, the same experimental
protocol was repeated, with the exception that a glucose
polymer plus fructose
(ratio of 1.8/1.0; exceed fluid,
replacement energy drink, Ross Laboratories,
Columbus,
OH) was added to the CON drink at a concentration
of
7.5% (0.27 g CHO/kg body w-t). Thus the drink volume,
flavoring, and times of ingestion were identical to those
of the CON trial. Although initially the subjects were
told that they were going to ride to fatigue, they were
stopped at the same time that they fatigued on the first
ride during the CON trial. As in the CON trial, once the
subjects were biopsied after exercise, they were asked to
continue cycling to fatigue; again, no drink was ingested
during the second ride.
The biopsy order between legs was rotated between
treatments
[in CON, biopsies were from the right leg at
rest in 4 subjects and from the left leg in the other 5
subjects; in CHO, the first biopsy was always taken from
the contralateral
leg (vs. CON)]. In all cases, postexercise
biopsies were taken while the subject was still seated on
the ergometer. The time between termination
of exercise
and freezing of the biopsy averaged 18 t 2 and 19 t 2 s
during the CON and CHO trials, respectively
(P > 0.05).
The time between the end of the first ride and beginning
of the second ride within a treatment
(due to the biopsy)
was -30-60 s on both occasions.
Analytical methods. All biopsies were quick frozen (~2
s after excision) in the needle in liquid Freon, maintained
at its freezing point (-150°C)
with liquid N2. The biopsies were stored in liquid N2 until analysis. Biopsies were
freeze-dried, dissected free of solid nonmuscle constituents (connective tissue and blood), powdered, and thoroughly mixed. The powder was divided into several aliquots. These aliquots were extracted and analyzed for
metabolites by enzymatic methods (4, 20) as previously
described (24). In addition, acid extracts were also analyzed for aspartate (20). Quantitation
of adenine nucleotides, nucleosides, NAD+, hypoxanthine,
and xanthine
was performed by reverse-phase
high-performance
liquid
chromatography
(28). Muscle metabolites, except for lactate, pyruvate, and glucose (due to their extracellular
presence), were normalized
to the mean total creatine
content [sum of phosphocreatine
(PCr) and creatine
IMP
IN
MUSCLE
(Cr)] for the whole material (117.1 t 1.9 mmol/kg dry
wt) to correct for variability
in solid nonmuscle constituents between biopsies.
Blood samples were drawn, anaerobically,
and immediately injected into tubes containing EDTA. The samples were left on ice for 10 min and centrifuged
at 4°C.
The plasma was aspirated and stored at -80°C until
analysis.
Plasma was analyzed for insulin by radioimmunoassay
(Diagnostics
Products, Los Angeles, CA),
free fatty acids by an enzymatic method (Zl), and glucose
and lactate as described for muscle (24).
Whole body respiratory
exchange was measured by
continuous
collection of 30-s aliquots of expired air and
analyzed for fractional components
of 0, and CO2 (Applied Electrochemistry
S-3Al and CD-3A, respectively,
Sunnyvale, CA) with an on-line system. Ventilation
was
measured with a turbine transducer
gas flow meter
(Pneumoscan
S-300, Sylmar, CA). Heart rate was monitored by telemetry.
Statistics. Significant differences between means were
determined with Student’s paired t test. Statistical
significance was set at P 5 0.05. Values are reported as
means t SE unless otherwise
indicated.
RESULTS
Performance
and cardiorespiratory
variables. During
the first ride in the CON treatment,
exercise duration
averaged 135 t 17 min (time to fatigue). The subjects
were thoroughly fatigued as evidenced by their ability to
cycle for only 0.6 t 0.2 min during the second CON ride.
During the first ride in the CHO treatment,
exercise
duration was identical to that during the first ride of the
CON treatment. However, the subjects were able to cycle
for 21.6 t 3.7 min during the second CHO ride (P 5
0.001 vs. CON), demonstrating
the performance-enhancing effect of exogenous CHO.
Heart rate and Vo2 increased steadily during exercise,
as previously observed (24), with no differences between
treatments,
with the exception of a slightly lower Vo2 at
the end of exercise in the CHO trial (Table 1). This may
be due to the higher rate of CHO oxidation, which results
in a higher caloric yield per 1 O2 consumed (vs. fat
oxidation). There were no significant differences between
treatments
in respiratory
exchange or substrate utilization during the initial phase of exercise. However, during
the latter phase of CHO exercise, the subjects relied more
heavily on CHO oxidation for aerobic ATP production.
These results are in agreement with those previously
observed under similar conditions (11).
Muscle metabozites. Glycogen contents were not significantly different
between treatments
at rest but were
significantly
higher after exercise in the CHO group
(Table 2). However,
we could not detect a significant
difference
in glycogen utilization
between treatments
(CON, 539 t 22; CHO, 506 t 32 mmol glucosyl units/kg
dry wt; P > 0.05). Intracellular
glucose was low in all
cases. Lactate and alanine contents were similar at rest
but were significantly
higher after exercise in the CHO
group. The sum of the post-phosphofructokinase
(PFK)
intermediates
(lactate + pyruvate + alanine) was significantly higher in the CHO group after exercise (12.0 +-
CARBOHYDRATE
TABLE
AND
IMP
IN
c73
MUSCLE
1. Cardiorespiratory variables at rest and during exercise
Duration
Parameter
Heart
rate,
beats/min
CON
CHO
CON
CHO
CON
CHO
CON
CHO
CON
CHO
VO,, l/min
RER
Carbohydrate
oxidation,
Fat oxidation,
g/min
g/min
Rest
15
60
60t3
66t3
157t3
160t3
2.96t0.14
3.04t0.15
0.88kO.01
0.88rtO.01
2.06t0.21
2.25t0.18
0.59t0.05
0.60t0.06
169k4
16823
3.30t0.18
3.22t0.17
0.86t0.01
0.89t0.01'"
2.27t0.22
2.20t0.28
0.72t0.05
0.66t0.10
0.29~0.01
0.31~10.02
0.82kO.04
0.78t0.02
0.10t0.04
0.06t0.02
0.07t0.02
0.09Ik0.01
Values are means t SE from 5-8 subjects. RER,
was 135 t 17 min. *P 5 0.05, j-P 5 0.01 vs. CON.
respiratory
exchange
2. Muscle contents of glycogen,
glycolytic intermediates, and amino acids
TABLE
Rest
Exercise
CON
Glycogen
Glucose
Intracellular
glucose
Pyruvate
Lactate
Alanine
Glutamate
Aspartate
CHO
CON
CHO
642t43
2.4t0.5
73t20
1.8t0.3
135t38*
4.lkO.45
612t21
1.7t0.1
0.25t0.11
0.46kO.15
0.13-+0.02
4.1t0.6
0.12t0.02
4.1t0.9
0.16t0.04
6.6t0.9
5.7t0.5
5.2t0.9
4.5kO.4
2.6t0.2
5.0t0.4
14.4kO.5
l.OkO.1
0.78kO.31”
-0.50t0.28
15.2t0.9
1.1t0.2
ratio
min
17lk4
172t4
3.44t0.24
3.37t0.22
0.83t0.02
0.86+0.01-j1.83t0.26
2.18+0.25"f
0.93kO.08
0.74+0.08-f
control;
CHO,
of exercise
176t3
176t3
3.52t0.19
3.42t0.17*
0.8320.02
0.86*0.01*
1.8lt0.21
2.llkO.17"f
0.96rtO.07
0.86t0.09"
carbohydrate.
End of exercise
9.5tl.l*
A
2-50
n
Garbo
hydrate
3n - B
3-U
Exercise
CON
CHO
CON
CHO
20.0tl.7
16.7kl.8
20.3tl.6
17.821.7
19.4tl.6
8.9tl.6
18.7tl.3
6.2k0.9
2.2rt0.6
0.47t0.03
0.25t0.03
1.5t0.3
0.47t0.03
0.28kO.03
6.6tl.7
0.43t0.05
l.Olt0.12
lO.Ortr:l.2
0.54rto.04
1.49t0.27
0.09t0.02
0.11t0.02
0.24&0.03
0.32t0.04
and are given
-*Control
3. Contents of carnitines and tricarboxylic
acid cycle intermediates in muscle
8 or 9 subjects
carbohydrate.
End
0.20t0.03
TABLE
Values are means & SE from
kg dry wt. CON, control;
CHO,
120
exercise in the CHO group, but the differences did not
reach statistical significance. However, the sum of these
three TCAI was significantly higher after exercise in the
CHO group (Fig. 1). This probably reflects an expansion
of the total TCAI pool since these TCAI account for
>70% of the total TCAI pool (3). The sum of the hexose
monophosphates (HMP) was also significantly higher
after exercise in the CHO group, whereas the accumulation of IMP was markedly attenuated.
8.5+0.8-f
5.3t0.3*
2.8k0.2
Rest
CON,
(VCO,/VO,);
Values are means ~fi SE from 8 or 9 subjects and are given in mmol/
kg dry wt, except glycogen
which is given in mmol glucosyl
units/kg
dry wt. CON, control;
CHO, carbohydrate.
Intracellular
glucose was
calculated
from total muscle glucose minus extracellular
glucose, assuming 0.3 1 extracellular
water/kg
dry wt at rest and 0.52 1 extracellular
water/kg
dry wt after exercise and that the plasma glucose concentration at the time of biopsy reflects the glucose concentration
in the
extracellular
space (16). * P I 0.05, t P 5 0.01, $ P 5 0.001 vs. CON.
Total carnitine
Carnitine
Acetylcarnitine
Citrate
Malate
Fumarate
of Exercise,
Treatment
r’
i?
u
F
1.5
-
5
i
0
in mmol/
1.5 vs. 18.2 t 3.0 mmol/kg dry wt; P 5 0.01). Glutamate
decreased and aspartate increased to similar extents in
both treatments during exercise.
Total carnitine remained constant, whereas free carnitine decreased during exercise under both conditions
(Table 3). Acetylcarnitine increased during exercise under both conditions, but there was no significant difference between treatments. This suggests that the availability of acetyl CoA was also not different between treatments, since the carnitine acetyltransferase reaction is
close to equilibrium (see Ref. 8). The individual TCAI
(citrate, malate, and fumarate) tended to be higher after
0.6
Rest
End of Exercise
x
II
I.
*
A 1
1
FIG. 1. Sum of hexes le monophosphates
(A; glucose
l-phosphate,
cTllrncIo
G-nhncnhatP
snC
,J
fructose
6-phosphate),
sum of tricarboxylic
Y~“~~
acid cvcle” rL~“ur~~u”v’
intermediates
(B). and IMP contents
(C) in muscle. Values
are means rt SE from 9 subjects. * P 5 0.05.
' '
c74
CARBOHYDRATE
AND
There were no significant
differences between groups
in high-energy
phosphates,
nor in the catabolites
of
adenine nucleotides
(except for IMP) at rest or after
exercise (Table 4). The NAD+ content was slightly but
significantly
higher after exercise in the CHO group.
Plasma met&o&es.
During exercise in the CON condition, plasma glucose decreased from 4.90 t 0.06 mmol/
1 at rest to 4.38 t 0.18 mmol/l at fatigue (Fig. 2). In
TABLE 4. Muscle contents of high-energy phosphates,
purine nucleotide catabolites, and NAD+
Rest
Exercise
CON
PCr + creatine
PCr
ATP*
ATP
ADP
AMP
NAD’
Adenosine
Inosine
Hypoxanthine
Xanthine
114.7t2.1
79.5t1.7
25.2t0.6
23.1-b0.5
2.8kO.l
0.12t0.01
CHO
CON
112.1t2.8
78.4t1.3
25.8t0.7
24.7t0.7
3.OkO.2
0.13-t-0.02
CHO
40.3&-4.0
118.4t4.8
43.3t2.9
23.3t0.8
22.0&l..
2.9kO.l
O.lltO.O1
24.2t0.7
23.3t0.6
2.8-tO.l
O.llt0.01
123.2k4.1
1.9tO.l
2.1kO.2
1.8tO.l
0.02t0.01
0.28t0.02
0.05t0.01
0.12t0.02
0.03t0.01
0.21-1-0.03
0.05kO.01
O.lltO.O1
0.04t0.01
0.25t0.03
0.08~0.02
0.10t0.02
1.9+0.1$
0.03+0.01j0.24t0.03
0.06kO.01
0.09t0.02
Values are means t SE from 9 subjects and are given in mmol/kg
dry wt. CON,
control;
CHO,
carbohydrate;
PCr, phosphocreatine.
* Measured
enzymatically.
T P 5 0.05, $ P 5 0.001 vs. CON.
7
Glucose
**
4
40
Insulin
IMP
IN
MUSCLE
general, those subjects who had the lowest plasma glucose
concentrations at fatigue (CON) also had the lowest
glycogen and highest IMP contents in muscle. During
the CHO trial, glucose increased from 4.96 t 0.10 mmol/
1 at rest to 6.54 +- 0.31 mmol/l after 1 h of exercise and
was 5.75 & 0.19 mmol/l at the end of exercise. Insulin
was significantly higher during exercise in the CHO
group. The increase in free fatty acids seen during exercise in the CON condition was completely abolished
during the CHO experiment. Presumably, this can be
attributed to the higher insulin concentration (a potent
antilipolytic hormone) and/or a lower epinephrine concentration (12, 25), epinephrine also being a potent lipolytic hormone. Plasma lactate was fairly constant during exercise but increased slightly at the end of exercise
in the CON condition. This has been observed previously
(11) and may be attributed to a catecholamine-mediated
stimulation of glycogenolysis (and glycolysis) in muscle
not participating in the exercise (1).
Relationship between muscle metabolites. There was an
inverse relationship between the muscle glycogen and
IMP contents during exercise, regardless of the treatment (Fig. 3). These results indicate that a marked
acceleration of IMP formation would occur when a glycogen content of -50 mmol glucosyl units/kg dry wt is
reached. When we plotted the results from a recent study,
where multiple biopsies were taken throughout exercise
(24), a similar curve was observed (data not shown). At
the end of the CON exercise there was an inverse relationship between IMP and HMP, but the relationship
was not apparent after CHO exercise (Fig. 4). There was
a linear relationship between HMP and glycogen after
CON exercise (r = 0.85; P 5 0.05), but again the relationship was not present after CHO exercise (r = 0.41;
P > 0.05).
*
DISCUSSION
E
3
3
20
CHO and fatigue. We have recently presented the
following scenario to describe the link between glycogen
depletion and muscle fatigue during submaximal prolonged exercise (24). The decrease in the availability of
CHO results in decreased levels of post-PFK intermediates, resulting in a decreased flux through some of the
anaplerotic reactions (alanine aminotransferase and pyruvate carboxylase), and hence a decrease in the TCAI.
0
4
Lactate
I
I
0
1.2
Free fatty acids
Rest
60
Duration
18;
Glycogen
(min)
and insulin concentrations
in plasma.
means & SE from 5-8 subjects. l , Control;
0, carbohydrate.
** P L 0.01, *** P 5 0.001 vs. control.
FIG.
2. Metabolite
12;
of Exercise
Values are
* P 5 0.05,
(mmol
glucosyl
units/kg
3. Relationship
between IMP and glycogen
at the end of exercise. l , Control;
0, carbohydrate.
y = 1.481 - (0.605
log [xl).
FIG.
dry
wt)
contents
in muscle
r = 0.74; P 5 0.01;
CARBOHYDRATE
AND
IMP
IN
MUSCLE
c75
of acetyl CoA (see RESULTS) but can apparently reverse
or attenuate many of the changes observed during the
latter stages of prolonged exercise (e.g., decrease in HMP,
3-carbon intermediates, and TCAI and increase in IMP)
and delay muscle fatigue. It should be noted that the
reversal of TCAI in our previous study was found in
untrained subjects, whereas the present study was performed on endurance-trained subjects. It is likely however that a reversal of TCAI will also occur in trained
subjects because they show an increase in malate during
the initial several minutes of submaximal exercise (-70%
vo 2max) that is even greater than that of untrained
subjects (l5), and is approximately fourfold higher than
the value at fatigue (CON) in the present study.
Using another model of CHO deficiency (McArdle’s
0
disease), others have shown that increasing the availa0
bility of glucose [by intravenous infusion of glucose or
glucagon (stimulates hepatic glycogenolysis)] decreases
0 0 O0
0
the formation of purine nucleotide catabolites during
0
0
0-c
1
exercise (18, 22). Thus our current data suggest that the
0
2
previous hypothesis describing the link between CHO
I: HMP (mmol/kg
dry wt)
availability and fatigue (24) is correct.
The present data also indicate that the immediate link
FIG. 4. Relationship
between
IMP and the sum of hexose monobetween glycogen and the post-PFK intermediates is the
phosphates
(HMP)
in muscle at the end of exercise.
l , Control;
0,
carbohydrate.
Top panel: r = 0.95; P IS 0.001; y = 1.027 - (2.662 log
HMP pool. As the glycogen content approaches low
[xl). Bottom panel: r = 0.41; P > 0.05.
levels, the formation of HMP will decrease, and consequently, flux through PFK and formation of three-carConsequently, flux through the TCA cycle should debon intermediates will drop. Consequently, increases in
crease (see the introduction),
and the mitochondrial
the relevant species of ADP and AMP will occur (actiNADH content should drop. This should result in a
vators of PFK), and this will also result in deamination
decrease in the rate of oxidative phosphorylation. However, the NADH content remains elevated, which coupled of AMP to IMP (17). The inverse relationship between
IMP and HMP (Fig. 4, top) and the fact that other
with the finding that the acetyl CoA content is-not
treatments which result in attenuated contents of HMP
reduced (probably due to the increase in fat oxidation)
(e.g., infusing propranolol or depleting the muscle glysuggests that flux through the TCA cycle is maintained
cogen
store before the exercise) during exercise also
(24). Presumably, this is explained by increases in the
free concentrations of ADP during contraction at the result in excessive accumulation of IMP (7, 26) support
enzymatic site [PFK, creatine kinase, AMP deaminase this explanation. The observation that the relationship
between IMP and HMP at the end of exercise was not
(in cytosol), and isocitrate and Z-oxoglutarate dehydroapparent during the CHO treatment may be related to
genases (in mitochondria)]. The increase in ADP will
result in a further decrease of PCr and an increase in Pi, the finding that the “critical” content of HMP was not
as well as activate the mitochondrial dehydrogenases (13, reached. Thus it would be difficult to detect a relation29), resulting in a maintained level of NADH. ADP and ship under conditions in which only small and relatively
Pi will also stimulate oxidative phosphorylation (9, 30), uniform changes are occuring in a variable (IMP).
The anaplerotic reactions that are potentially involved
resulting in a maintained rate of aerobic ATP synthesis.
However, the increase in free ADP (in cytosol), coupled in expansion of the TCAI have been described previously
with a decreased capacity to rephosphorylate ADP Tdue (3, 24). It has been suggested that the alanine aminoto low PCr content and decreased glycolytic flux (see transferase reaction (pyruvate + glutamate + alanine +
2-oxoglutarate) plays an important role in expansion of
below)], will result in an increase in free AMP (in cytosol) (via adenylate kinase). When the increases in the TCAI in human skeletal muscle (24, 27). The present
findings are consistent with this hypothesis.
relevant species of ADP and AMP (free concentrations
Source of H2Mp. The present findings demonstrated
during the contraction in the immediate vicinity of AMP
deaminase) become excessive, AMP will be deaminated that the HMP pool was significantly lower after exercise
to IMP (17). [It should be noted that the creatine kinase in the CON group. The relationship between HMP and
and adenylate kinase equilibria cannot be used to calcu- glycogen contents in muscle at the end of exercise in the
late the relevant increases in ADP and AMP (23).] Thus
CON trial suggests that in this case glycogen was the
the increase in IMP reflects a decline in cellular phos- major source of HMP formation. However, the relationphate potential (ATP/[ADP
X Pi]), and it is likely that
ship between HMP and glycogen was no longer apparent
the decrease in phosphate potential is related to the at the end of CHO exercise, which suggests that at least
impairment of the contractile process (24).
part of the increase in HMP was due to greater utilization
The present data demonstrate that the supply of ex- of extracellular glucose (2), or that some other factor
ogenous CHO does not significantly affect the content
obscured the relationship.
1
C76
CARBOHYDRATE
AND
We are grateful
to Nancy Cain, Paul Crowley,
and Glen Daniels for
technical
assistance.
This research was supported
by a grant from Ross Laboratories.
Address for reprint
requests: A. Katz, Dept. of Kinesiology,
Univ. of
Illinois,
906 S. Goodwin
Ave., Urbana,
IL 61801.
Received
19 October
1990; accepted
in final
form
11 February
1991.
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