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

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Chapter | 15 Skeletal Muscle Function
(a)
(b)
(c)
FIGURE 15-2 Muscular contraction involves the shortening of sarcomeres
by sliding of the overlapping arrays of thick (myosin) and thin
(actin) myofilaments. The energy for contraction is derived from the
hydrolysis of ATP in the presence of an actin-activated ATPase present
within the head regions of the myosin thick filament cross-bridges. The
ATP is generated by the energy metabolism of the myofiber, principally
by anaerobic glycolysis or oxidative phosphorylation. The utilization of
ATP may be direct from those sources or indirect from the phosphorylation
of ADP from creatine phosphate by creatine kinase (CK).
of constituent proteins that form the sarcomere: contractile,
regulatory, and structural.
FIGURE 15-3 Schematic presentation of myosin cross-bridges on thick
myofilaments. Portions of the myosin molecules (cross-bridges) project
from the thick myofilaments and make contact with the thin myofilaments
(a). The light meromyosin (LMM) portion of myosin molecules forms the
major structural component (backbone) of the thick myofilament, whereas
the heavy meromyosin (HMM) component forms the cross-bridge connections
between the thick and thin myofilaments (b). The cross-bridges
of myosin are composed of two fractions: (1) the S 1 fraction, a globular
protein fraction composed of two heads, each possessing binding capacities
for ATP and actin and the actin-activated ATPase activity of myosin,
and (2) the S 2 fraction, a fibrous protein fraction that forms the flexible
linkage between the S 1 fraction and the LMM portion of myosin (b). The
force for sliding of the myofilaments results from a change in the angle of
attachment (i.e., a change from 90 to 45 degrees) between the S 1 globular
head and actin filament (c).
1 . Myofi laments and Contractile Proteins
Together, myosin, the principal contractile protein component
of thick myofilaments, and actin, the principal component
of thin myofilaments, account for more than 70% of
myofibrillar protein. Lateral projections of the myosin thick
myofilaments (myosin cross-bridges) form reactive sites
with actin, which cyclically associate and disassociate during
contraction and relaxation. The force-generating step for
sliding of the filaments past each other results from changes
in the angle of the cross-bridge attachments ( Fig. 15-3 ).
a . Thick Myofilaments and Myosin
To understand the physicochemical changes that occur at
the cross-bridges, the composition and properties of myosin
need to be considered. Myosin is an asymmetric protein with
both structural and enzymatic properties. It is composed
of two identical heavy chains (polypeptide chains with an
approximate molecular mass of 200kDa) and two pairs of
light chains (polypeptide chains with molecular masses
ranging from 16 to 27kDa). The two myosin heavy chains
are arranged in a double helix to form a long stable tail at
one end, and at the other end each heavy chain is folded to
form one globular pear-shaped head. The four myosin light
chains are contained within the globular heads (two per
head) near the junction of the head and neck domains.
The composition of myosin heavy chains within sarcomeres
varies among species, among individual muscles, and
among individual muscle cells. Mammalian skeletal muscle
cells may express six distinct heavy chain genes: perinatal
(or neonatal), fast type IIa, fast type IIx (or IId), fast type
IIb, and extraocular. The speed of contraction of these myosin
heavy chain isoforms increases in the order listed here.
Three additional sarcomeric myosin heavy chain genes
(super fast, slow A, and slow B) exist, but their expression
is unknown, with the exception of expression of superfast
myosin in jaw muscles ( Sweeney and Houdusse, 2004 ).
A range of myosin light chain isoforms also exist in
skeletal muscle that may affect their function. Skeletal
muscle possesses both fast skeletal and slow skeletal muscle
isoforms of essential light chains as well as regulatory
light chains. Biochemically, two classes of light chains
can be distinguished: (1) two identical DTNB light chains,
which disassociate from their globular heads with the thiol
reagent 5,5 -dithiobis(2-nitrobenzoic acid) (DTNB), which
correspond to regulatory light chains, and (2) two related