section 21.3
Energy Supply in Muscle
469
to the cytochromes via
j3
-oxidation of fatty acids and via
glycolysis and the tricarboxylic acid (TCA) cycle. Type I
fibers usually have only modest activity of glycolytic en-
zymes and myokinase, and normally do not produce pyru-
vate at rates much in excess of the rate at which they can
oxidize it. Type lib fibers are metabolically the mirror
image of type I, and type Ha is a mixed fiber type meta-
bolically.
Ordinarily, slow-twitch oxidative fibers are the first re-
cruited, and if the force and speed thus produced are ad-
equate for the task, they are the only fibers recruited. The
relatively low actomyosin ATPase activity of these fibers
enables production of tension with less ATP expenditure
than in fast fibers, and so, at the low speeds characteristic of
prolonged work, they are more efficient than faster fibers.
Aerobic energy production in these fibers offers many im-
portant advantages over the low-oxidative high-glycolytic
strategy of lib fibers. First, complete oxidation of glucose
yields 18 times as much ATP per glucose as glycolysis
only. Second, the metabolites are CO
2
, which is easily
eliminated via the lung, and H
2
0, which is needed during
work. This is in contrast to the lactic acid produced in gly-
colysis, which lowers pH considerably until it can be me-
tabolized aerobically. Low intramuscular pH inhibits SR
Ca2+ release, impairs activation, and slows cross-bridge
cycling. Third, glucose is the only available substrate for
glycolysis, while oxidative metabolism can also consume
lipid and amino acids in addition to glucose. This latter
feature enables a vastly greater volume of work to be
performed aerobically than anaerobically, even when the
anaerobic work is intermittent to allow recovery from the
lactic acidosis. A typical value for glucose stored as glyco-
gen in muscle is about 430 g, and about 70 g in liver, equiv-
alent to
2 1 0 0
kcal total (or roughly the energy needed to
run
2 0
miles, assuming that all of it could be metabolized).
Lipid stores in adipose tissue, muscle, and elsewhere are
typically 5.5 kg in an active young adult male, equivalent
to almost 52,000 kcal (or enough energy to run more than
500 miles, again assuming that all of it could be metabo-
lized), and this is in a relatively lean person. The deriva-
tion of tricarboxylic acid (TCA) cycle intermediates from
some amino acids and the conversion of glycogenic amino
acids to glucose enables protein to also serve as an energy
source. For these reasons, the energy substrate available to
the slow oxidative fibers is almost inexhaustible, and, due
to their low actomyosin ATPase activity, replenishment of
ATP by oxidative phosphorylation can keep up with ATP
hydrolysis. Thus, SO fibers are fatigue-resistant, while fast
glycolytic fibers which use only glucose (and inefficiently
at that) are quite fatiguable. The intermediate FOG fibers
are much more fatigue-resistant than FG fibers, but less so
than SO fibers.
An additional consideration is that each gram of glyco-
gen stored is associated with 3—4 grams of water, so that the
energy per gram of wet weight (about 4 kJ/g) is much lower
than for lipid (39 kJ/g). Carrying stored energy around as
lipid is therefor less expensive than carrying it as carbohy-
drate, but only the aerobic fiber types draw significantly
upon this store. When malnourished persons are fed, there
is rapid synthesis of glycogen, with a corresponding move-
ment of water into the cells (primarily in muscle and liver,
where glycogen synthase activity is high). Potassium is the
predominant intracellular cation, so there is also a move-
ment of K+ into cells. Since muscle may be half the body
mass, and since malnourished persons are often hypov-
olemic, these movements are proportionately large. The
resulting
hypokalemia
and further
hypovolemia
may be
fatal unless adequate hydration and K+ supplementation
are provided.
Aerobic fiber types have high activities of the enzymes
for /
1
-oxidation of lipid, and their mitochondria also have
abundant acylcarnitine palmitoyltransferases and associ-
ated substances (Chapter 18). However, the low solubility
of fatty acids limits their rate of diffusion through aqueous
media, and the numerous steps involved in mobilizing fatty
acids from triacylglycerols, activating them to acyl-CoA
and transporting them into mitochondria, and splitting off
two-carbon pieces as acetyl-CoA, also slows flux through
fi
-oxidation. The net result is that the rate of ATP pro-
duction attainable by this pathway is about one half the
maximum rate achievable by aerobic glycolysis.
When the volume of work is such that glycogen is func-
tionally depleted, muscle power output must decrease to
the level that can be supported by fatty acid oxidation.
During prolonged moderate-intensity exercise, most of the
fatty acid oxidized is derived from lipolysis in adipose tis-
sue during the exercise. Regulation of lipolysis varies re-
gionally in humans: the exercise-induced lipolysis is 50%
greater in abdominal than in gluteal adipocytes, but the un-
derlying biochemical differences have not been explained.
Adipocyte lipolysis depends at least in part on activation
of lipoprotein lipase by catecholaminergic stimulation and
other hormonal changes accompanying exercise, and takes
many minutes (20—40) to fully accelerate. In the shorter
term, and in higher intensity work where the metabolic de-
mand exceeds the cardiovascular delivery of lipid, lipol-
ysis of triglyceride droplets stored in the muscle fibers
becomes the most important source of fatty acids. Type I,
and to a somewhat lesser extent type Ila, fibers store appre-
ciable triglyceride, presumably by esterifying fatty acids
from the blood since activity of enzymes involved in lipid
synthesis is low in human muscle. Lipid storage in muscle
increases with endurance training. Utilization of lipid pre-
viously present in the plasma as protein-bound fatty acids
