Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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Chapter | 15 Skeletal Muscle Function
the rate-limiting step in glycolysis, and possibly impair muscle
contractile mechanisms ( Sahlin et al. , 1981 ). Muscle pH
can fall as low as 6.4 following maximal exercise. However,
more recent studies show that PKF activity is not inhibited at
pH 6.4 ( Spriet, 1991 ), and hydrolysis of ATP, which generates
ADP, free phosphate, and hydrogen ion, is a more likely
source of acidosis than lactic acidosis ( Lindinger et al. ,
2005 ; Robergs et al. , 2004 ). When ATP demands of muscle
are met by mitochondrial respiration, hydrogen ions are used
by the mitochondria for oxidative phosphorylation. With
maximal exercise, when ATP is largely generated by glycolysis,
hydrogen ions accumulate creating an acidosis. Under
more current thinking, lactate is generated to prevent pyruvate
accumulation and generate NAD to facilitate glycolysis
and serves as an anion to actually buffer hydrogen ion
accumulation ( Lindinger et al. , 2005 ). Thus, lactate serves
as a marker for acidosis but is not directly involved in acidotic
conditions within muscle cells ( Lindinger et al. , 2005 ).
The ability to buffer or remove hydrogen ions remains very
important for muscle function during maximal exercise.
Further metabolic limitations to maximal high intensity
exercise may relate to the demand for ATP outstripping the
myofiber ’ s innate ability to produce ATP at maximal speeds.
Under these circumstances, the cell turns to its last venue of
energy production, the purine nucleotide cycle ( Harris et al. ,
1991 ). Short term, this produces ATP for muscle contraction
from the accumulated ADP. However, the total nucleotide
pool becomes depleted from deamination of AMP to IMP.
For intracellular stores of ADP and ATP to be replenished, at
least 30 to 60 min is required for reamination of IMP. Whole
muscle concentrations of ATP rarely decline by more than
50% with maximal exercise; however, ATP in individual
fibers during maximal exercise can be minimal, and concentrations
in individual fibers may be more important for the
onset of fatigue than the measured concentrations in whole
muscle samples ( Essen-Gustavsson et al. , 1997 ).
A more complex model of fatigue has recently been
developed that refutes the classic model of peripheral fatigue
of muscle contraction arising from inadequate oxygen delivery
or substrate depletion. In this newly proposed model,
fatigue is not a physical limit within muscle but rather a sensation
that arises from conscious perception of subconscious
regulatory processes in the brain that control muscle fiber
recruitment. Termination of exercise occurs when a conscious
desire to continue exercising is overridden by the summation
of negative sensations arising from afferent feedback
from physiological systems that would include sensors of
substrate availability and muscle pain ( Noakes et al. , 2004 ).
B . Adaptations to Exercise Training
Exercise induces major biochemical adaptations in skeletal
muscle. The nutritional state, intensity and duration
of exercise, and degree of physical fitness are all factors
that qualitatively and quantitatively affect the metabolic
pathways used in the generation of energy for muscular
contraction.
The principal metabolic adaptation of skeletal muscles
to training is an increase in the oxidative capacity to utilize
fat, carbohydrate, and ketones ( Grobler et al. , 2004 ; Hurley
et al. , 1986 ). Muscle glycogen content often increases with
training ( Gollnick et al. , 1972 ), whereas glycogenolytic and
glycolytic enzyme activities are largely unchanged ( Baldwin
et al. , 1973 ; Holloszy, 1982b ). In contrast, the mitochondrial
protein content increases approximately 60% with training
( Holloszy, 1982b ). The activities of enzymes that transport
FFA into the mitochondria, the capacity for oxidation of
FFA, as well as the activities of oxidative enzymes in the
citric acid cycle increase in response to a training program
(Gollnick et al. , 1972 ; Holloszy, 1982b ; Mole et al. , 1973 ;
Saltin et al. , 1977 ). In horses, training studies most frequently
show increased activities of oxidative enzyme markers
such as citrate synthase and variable to no measurable
increase in markers for fat oxidation such as 3-OH-acyl-
CoA dehydrogenase and glycolysis ( Cutmore et al. , 1986 ;
Golland et al. , 2003 ; Hodgson, 1985 ).
Histochemical studies show that the increase in oxidative
capacity that occurs with training occurs most notably
in type 2 and particularly type 2x (IIB) fibers of horses and
the capillarization of all fiber types increases ( Henckel,
1983 ; Serrano et al. , 2000 ; Yamano et al. , 2005 ). Most
studies indicate that over time the cross-sectional area of
type 2x (IIB) muscle fibers decreases with training and
type 1 and type 2a fibers increase in size ( Rivero et al. ,
1993 ). These metabolic adaptations favor the delivery of
oxygen and blood-borne substrates, the early activation
of oxidative metabolism, and the utilization of FFA in
muscle fibers. By sparing muscle glycogen, endurance is
enhanced, and fatigue is delayed. At high exercise intensities,
improved oxidative capacity decreases the rate of
hydrogen and lactate ion accumulation in trained versus
untrained subjects performing the same exercise. Although
an increase in oxidative capacity may be metabolically
advantageous, a decrease in the percentage of type 2x
fibers and a decrease in their cross-sectional areas may also
deleteriously affect their speed and force of contraction.
Obviously a balance is required between skeletal muscle
fiber metabolic and contractile properties for optimum
speed and endurance. Because the muscle fiber composition
and fiber properties vary so greatly among individuals,
achievement of this balance may be different for each
horse and each type of equestrian competition.
In summary, the major metabolic consequences of the
adaptations of muscle to endurance exercise are a slower
utilization of muscle glycogen and blood glucose, a greater
reliance on fat oxidation, and less lactate production during
a given intensity. At workloads below maximal O 2
utilization, aerobic pathways are the principal sources of
energy through the oxidation of FFA and glucose. This