Muscle and Nonmuscle Contractile Systems
F IG U R E 2 1-11
A simplified model of the interactions thought to occur during the cross-bridge cycle. Four major structural states are
depicted, but the actual number of structurally and energetically distinct states through which this system transitions is
uncertain. The vertical drop in the figure crudely represents the free-energy change in the transitions shown. The
functional change in myosin structure is shown as a change in the relative orientation of the neck (cross-hatched) to the
catalytic head region (hatched). A is actin,
is myosin, and P, is phosphate. M ■
ATP represents myosin complexed
with ATP immediately after detachment from actin. Here, the neck is shown in the same configuration as at the end of
the power stroke. Hydrolysis of ATP leads to M ■
with weak bonding to actin both before and after hydrolysis.
ATP hydrolysis is energetically favored, but due to the products remaining bound, the free-energy change is not large.
Hydrolysis is shown here as eliciting a change in orientation of the neck, producing the conformation thought to exist at
the initiation of the power stroke, but the relationship between the hydrolysis events and the mechanical events is still
speculative. Release of Pj from A ■
• ADP ■
Pj following binding to actin is associated with conformational changes
that produce the strained, or force-producing, state A M* - ADP. Transition from A ■
M* • ADP to A ■
coincides with
performance of mechanical work and formation of a very strong A •
bond, and a reorientation of the neck region is
thought to occur during this transition. In striated muscle, a large part of the free energy driving the cross-bridge cycle is
lost between these two states. A ■
M ■
ADP and A • M are thought to differ little in configuration, and the energy change
associated with ADP release is small. Subsequent binding of ATP to A ■
M dramatically lowers the affinity of myosin for
actin, probably producing release of M • ATP from A without altering the neck orientation, returning the system to the
state shown at the upper left. [Adapted from: R. Cooke, Actomyosin interaction in striated muscle.
Physiol. Rev.
671-697, 1997.]
hydrolysis is associated with return of the substrate bind-
ing site to its original orientation, and ADP and Pj are
released into solution.
It is important to note that this model predicts the hy-
drolysis of one ATP for every cross-bridge cycle of every
myosin head: there is evidence that, in high-speed con-
tractions at least, there may be multiple attachments and
detachments per hydrolysis. Thus, our understanding is
obviously not complete. Nevertheless, the ATP consump-
tion associated with contraction can be enormous. The
metabolic scope
(ratio of maximal to resting energy con-
sumption) of skeletal muscle can reach
1 0 0
, and there
must necessarily be metabolic specializations to meet this
peak demand and to do so quickly. Energy metabolism is
discussed in Chapters 13-15 and 18.
21.3 Energy Supply in Muscle
During muscle activation, ATP consumed by the myofib-
rils must be replaced by aerobic and/or anaerobic resyn-
thesis. The magnitude of the task is increased by the aug-
mentation of the SR Ca2+-ATPase activity that must also
take place. SERCA activity is not very great at rest, being
only about 7% of the resting energy consumption, but it
increases more than ten-fold during contraction. Na+, K+-
ATPase activity also increases due to the ion fluxes accom-
panying repeated action potentials. The metabolic special-
izations for meeting these demands vary by fiber type (see
Organization and Properties of Muscle Fibers,
p. 462).
Type I fibers are generally oxidative. Their ATP resynthe-
sis is largely dependent on supplying reducing equivalents
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