Muscle and Nonmuscle Contractile Systems
or as triglyceride can begin promptly, and is not dependent
on hormonal mechanisms. Activation of capillary lipopro-
tein lipase (e.g., by heparin) measurably increases muscle
lipid oxidation in endurance exercise.
Rate of lipid oxidation as a function of exercise intensity
is an inverted U shaped curve, increasing to a maximum
of roughly 40 /xM • kg
- 1
• min
- 1
at 60-70% of maximum
aerobic power, and decreasing to about three fourths of
this rate at 85% of maximum aerobic power. As the power
requirement approaches the limits of /3-oxidation, the flux
through glycolysis increases rapidly. In the rat, this has
been shown to cause increased citrate release from mi-
tochondria with a consequent increase in malonyl-CoA
synthesis via acetyl-CoA carboxylase (ACC). Malonyl-
CoA strongly inhibits carnitine palmitoyltransferase-1,
thereby inhibiting lipid oxidation (Chapter 18). However,
in humans, muscle ACC activity is low, as is malonyl-CoA,
and malonyl-CoA has not been found to be negatively cor-
related with rate of ^-oxidation. It seems unlikely that the
phenomenon is explained merely by competition for CoA
or for NAD, and so the mechanism is unclear. The signif-
icance is that as power output exceeds 70% of maximum,
aerobic glycolysis not only supplements /
-oxidation, it
progressively replaces it.
Type lib fibers rely on glycolytic rather than oxidative
metabolism for energy. In these fibers, glucose derived
from muscle glycogen and from glycogenolysis and glu-
coneogenesis in liver is split to pyruvate at rates far greater
than the rate at which pyruvate can be oxidized. Though
producing only 2 ATP per glucose molecule (3 per gluco-
syl unit from glycogen), these fibers can generate such a
high flux through glycolysis that the peak ATP production
rate is twice the maximum rate of oxidative ATP produc-
tion in type I fibers. Aerobic and anaerobic glycolysis are
discussed in Chapter 13.
phosphate to 1,3-bisphosphoglycerate by glyceraldehyde-
3-phosphate dehydrogenase (G3PD) requires reduction of
NAD to NADH. The NAD pool is small, and without rapid
oxidation of NADH back to NAD, glycolysis would im-
mediately stop at the G3PD step. Oxidation of NADH can
be accomplished by conversion of pyruvate to lactate via
lactate dehydrogenase (LDH). Maximum values of lactate
production in glycolytic fibers in humans range from 0.5
to 0.9 mM • g
• s_I, while in oxidative fibers it is only
0.25 mM • g
~ 1
s- 1. Since the maximal reported rates of ap-
pearance of lactate in blood are only one tenth the FG fiber
production rate, it is clear that the maximal production
rate far exceeds the efflux capacity and that high-intensity
exercise must necessarily produce high intramuscular lac-
tate concentration. Intramuscular lactate concentrations as
high as 45-50 mM/kg of cell water have been reported in
humans. Since the pK of lactic acid is 3.9, most (>95%)
of this acid will be dissociated in the physiological range
of pH, imposing an almost equimolar H+ load on the cell’s
buffer systems. Intracellular pH in muscle fibers is about
7.0, and decreases 0.4-0.8 pH unit during intense exercise.
Lactate efflux from muscle occurs by simple diffusion of
undissociated lactic acid and by carrier-mediated lactate-
proton cotransport. The latter probably accounts for
50-90% of the lactate efflux, depending on fiber type and
pH. It was thought that fast glycolytic fibers had an abun-
dant lactate transporter with a low
providing rapid ef-
flux to support continued glycolysis, while slow oxidative
fibers had a less abundant transporter or one with higher
or both, so that lactate would be retained as a redox
buffer. Retained lactate maintains an NAD/NADH ratio
that stimulates oxidation, and ensures subsequent oxida-
tion or gluconeogenesis in the muscle. There are three or
more muscle lactate transporters, one of which has been
sequenced in rat muscle and found to have 494 amino acids
(M.W. 53,000) and
8 6
% sequence identity with the cor-
responding protein from human erythrocytes. However,
for lactate has not been found to differ significantly
between fiber types, being around 30 mM. Moreover, the
transport capacity is almost twice as great in SO fibers as
in FG. The high
implies that most of the lactate pro-
duced will be retained during exercise regardless of fiber
type, and the relative amounts of carrier imply that lac-
tate efflux from FG fibers is greater than from SO fibers
only because the rate of production is usually much higher,
creating greater gradient for efflux. It follows that lactate
efflux from FG fibers is not adequate to prevent eventual
inhibition at the G3PD step and pronounced acidification
of the fibers. The greater lactate transport capacity of ox-
idative fibers also enhances lactate entry into these fibers
when blood lactate rises during moderate-intensity work
in which the SO fibers produce little lactate.
The fate of the lactate produced is primarily oxida-
tive (55-70%). Lactate released from muscle enters ex-
clusively oxidative tissues in which lactate concentration
is low (like heart, diaphragm and brain), is converted back
to pyruvate, and is oxidized. Retained lactate is oxidized to
generate ATP needed to replenish phosphocreatine stores
following exercise and to restore normal distribution of
Ca2+, Na+, and K+. About 15% is used in gluconeogene-
sis and subsequent glycogenesis. The balance is converted
to alanine, glutamate, or other substances.
Utilizing amino acids as fuel requires eventual elimina-
tion of an equimolar amount of ammonia, which may also
require eliminating more water. It also requires a longer re-
covery time, since replacement of the hydrolyzed proteins
may be slow, and requires higher dietary protein intake. In
most circumstances, protein is the macronutrient in least
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