MUSCLES

 Muscle is a major biochemical transducer

 Converts potential energy into kinetic energy

 Largest single tissue in the human body

 CLASSIFICATION OF MUSCLES

There are 3 basic types of muscle

• Skeletal muscle
• Cardiac muscle
• Smooth muscle
They are also divided into 2 based on
electron microscope appearance

•Striated eg cardiac and skeletal

•Non striated eg smooth muscles
Divided based on control from
the CNS
•Voluntary muscles eg skeletal muscles
• Involuntary muscles eg cardiac and
smooth muscles
 MUSCLE STRUCTURE
• Striated muscle is composed of multinucleated
muscle cells
• Surrounded by electrically excitable plasma
membrane , the sarcolemma
• A muscle fibre contains bundles of myofibril
arranged in parallel
• Embedded in ICF called sarcoplasm
• The sarcoplasm contains glycogen, ATP,
phosphocreatine and enzymes of glycolysis
 CONTD
• The sarcomere is the functional unit of the
muscle cell.
• The myofibril show alternating light(I)and
dark (A) bands.
• The central region of the A band (H zone) is
less dense.
• The (I) band is bisected by a dense and narrow
Z line.
Muscle Structure
• Each myofibril have a thick filament confined
to A band
• And a thin filament in the I band
• The thick filament contains myosin protein.
• The thin filament contains mainly ACTIN, with
TROPOMYOSIN and TROPONIN
• The thick and thin filaments interact via cross
bridges on the thick filament.
• Interaction between this cross bridges and
actin filament cause contraction
• The filaments slide pass one another during
contraction
• When muscles contract there is no change in the
length of the thick filament or of the thin filament
but the H zone and the I bands shorten.
• when a sarcomere contract, the z lines come
closer together and the I band becomes smaller.
• The A band stays the same width.
• At full contraction, the thin and thick filament
overlap.
 MUSCLE PROTEINS
THE BASIC MUSCLE PROTEINS ARE:
 ACTIN and MYOSIN
 Others are TROPOMYOSIN,TROPONIN and
alpha ACTININ
 ACTIN
• The major protein in the light band or thin
filament of the myofibril
• Comprises 25% of muscles protein by wgt
• The monomeric globular component is G-
actin.
• This polymerises non covalently to form F-
actin
• F-actin is an insoluble double helical filament
• G -actin contains ADP and forms the active site
for binding of the cross bridges.
• The myosin cross bridges attach to this active
site.
• It also has an ATP binding site
• Neither G nor F- actin exhibit any catalytic
activity
 MYOSIN
• Contributes 55% of muscle protein by wgt
• Forms the thick filament in the dark band
• Has a fibrous portion consisting of 2 intertwined helices
• Each has a globular head attached at one end
• The hexamer consist of one pair of heavy chain and 2
pairs of light chain.
• Skeletal muscle myosin exhibit ATPase activity
• It binds to F-actin during contraction via the cross
bridges.
 CONTD
• The protein is digested with trypsin to give 2
segments
• Light meromysin (LMM) and heavy
meromyosin(HMM)
• LMM are insoluble alpha- helical fibres
• They exhibit no ATPase activity and do not
bind to F-actin
• HMM can be further digested by papain
• 2 subfragment S1 and S2 are formed
• S1 fragment exhibit ATPase activity and bind
readily to actin
• S2 fragment is fibrous, no ATPase activity, does
not bind to actin
 TROPOMYOSIN
 This consists of two chains alpha and beta
chains.
 Attached in groove between the two actin
polymers.
 Blocks attachment sites of cross bridges on
actin filaments.
 Functions as a regulatory protein in muscle
contraction.
 Present in muscular and muscle like structures
 TROPONIN
 Found mainly in striated muscles.
 Also a regulatory protein in muscle contraction
 Consists of three components
 Troponin T
• Binds to tropomyosin and other troponin molecules
 Troponin I
• Has a strong affinity for actin
• Involved in inhibition F-actin –myosin interactions
• Binds to other troponin molecules
 CONTD
• Troponin C
• a calcium binding protein similar to
calmodulin in function
• Binds 4 molecules of calcium
 ALPHA-ACTININ
 An actin binding protein on the Z line
 F-actin molecules attach here
 MECHSM OF MUSCLE CONTRACTION
 Consist of cyclic attachment and detachment
of myosin to F-actin
 Actin filament and myosin slide pass one
another
 Energy utilized is supplied by ATP when
hydrolysed by myosin ATPase
 This is accelerated by binding to actin
 Ca2+ released from Sarcoplasmic Reticulum
binds to Troponin C(4mols)
 CONTD

• This uncovers the active sites of the actin for

myosin attachment
The biochemical cycle of muscle contraction
that follows consist of the following
• Myosin head attaches to the ATP molecule
• ATP is hydrolysed to ADP +Pi but not released
• myosin cross bridges attach to the active site
on the actin exposed by TpC
 Product of ATP hydrolysis released from Actin-
myosin complex
 Energy produced moves the angle of the cross
bridge head from 90 to 45 degrees.
 Causes pulling of the actin towards center of
the sarcomere
 Another ATP molecule binds to the myosin-
actin complex
 Myosin-ATP complex has a poor affinity for
actin
 Myosin head detaches from the actin causing
relaxation.
 ATP attached to the Myosin-ATP complex is
broken down again and another cycle continues
Note that ATP powers contraction and relaxation
of muscles
The biochemical cycle of muscle contraction
 Regulation of muscle contraction and
relaxation
• There are 2 basic mechanism
• Ca2+ plays a key role in this mechanisms
 ACTIN BASED REGULATION
• These occurs mainly in striated muscles
• The inhibitor of striated muscles is the
troponin system
• TpI prevents binding of myosin head to F-
actin active site
• this is by altering the conformation of F-actin
• Or by pulling in the tropomysin to block the
active site
• Thus preventing contraction
• This activity is regulated by the level of ca2+
released into the sarcoplasm
• when upto 10_5 mol/l it activates exposure of
active site
• When it decreases to about 10_7 mol/l
inhibition of the site continues
 MYOSIN BASED REGULATION
• This is synonymous with smooth muscle(sm)
• The troponin system is absent
• Contraction is also regulated by calcium ion
concentration
• Myosin attachment to actin does not generate
ATPase activity
• This is due to absence of other muscle
proteins
• A light chain is found in the SM myosin(p_light
chain)
• This prevents binding of the myosin head to
F- actin
• Phosphorylation of the P-light chain activates
the myosin –actin binding
• This activates myosin ATPase which
commences contraction cycle
• P-light chain is phosphorylated by a myosin light
chain kinase
• This is calcium dependent
• Found in the sarcoplasm of smooth muscles
• Calcium attaches to a protein calmodullin
forming calmodullin -4ca 2+
• when Ca2+ level is upto 10_5 mol/l the activated
light chain kinase phosphorylates the p-light
chain
 Cont’d
• This ceases the inhibition of the myosin –F-actin
interaction
• Then the contraction cycle begins
• Relaxation occurs when Calcium level falls below
10-7 mol/l.
• Ca2+ dissociates from the myosin light chain kinase
hence inactivating it.
• Thus stopping the phosphorylation of p-light chain.
• Also a light chain phosphatase removes existing
phosphates from p-light chain
• The dephosphorylated p-light chain inhibits
the binding of myosin to Actin
• In effect deactivates the ATPase activity
• The myosin detaches from F-actin in the
presence of ATP
• Relaxation then occurs
 COLLAGEN
• The name was derived from the greek word kolla
which means glue
• The most abundant protein in the body
• It provides an extracellular frame work for all
metazoan animals
• Forms a scaffold to provide strength and structure
• Although these molecules are found throughout the
body, their types and organization are dictated by
the structural role collagen plays in a particular
organ.
• It’s a triple helix coiled structure of
polypeptide subunits.
• Each chain contain about 1000AA
• Features a sequence consisting of glycine,
proline and hydroxyproline
• There 28 types of collagen but 5 distinct types
in the mammalian tissue
• Type 1- skin, tendon, vascular ligament, bone
• Type 11- cartilage
• Type 111- reticular fibres
• Type 1V- basal laminar, epithelium secreted
layer of the basement membrane
• Type V- cell surfaces, hair and placenta
• The polypeptides are bound in helices to form a stiff
rodlike molecule
• These associated longitudinally and bilaterally into
fibril
• Collagen fibril range from 10-100nm in diameter
• In the molecular structure glycine constitutes every
third residue in the triple helical structure of each
alpha chain
• This is represented by (gly-x-y) n where x and y are
other AAs
• In mammalian collagen about 100 of the x
position are proline and 100 of the y positions
are hydroxy proline
• The rigid amino acids increases the stability of
the triple helix by limiting rotation of the
polypeptide backbone
• The Hydroxyproline residue contribute
additional stability by forming intra molecular
hydrogen bonds b/w the polypeptide chains.
 COLLAGEN SYNTHESIS
• Collagen is synthesized as an intracellular
precursor by the fibroblast, osteoblast and
chondroblast
• This undergoes a post translational
modification b/4 becoming a mature fibril
• The earliest precursor is preprocollagen or
preproalpha chain
• This contains a signal or leader sequence of 100
AAs at its amino or N terminus
• Preprocollagen is generated by ribosomes
attached to the Endoplasmic Reticulum(ER)
• Released into the lumen of the ER, the signal
peptides are cleaved off
• The peptide chain is now called proalpha
chains
• Then hydroxylation of lysine and proline AA
occur inside the lumen
• Hydroxy proline is important in stabilizing the
triple-helical structure of collagen because it
maximizes interchain hydrogen bond
formation.
• Here ascorbic acid serves as a cofactor
• Then glycosylation of specific hydroxylysine
residues occur using glucose or galactose
• A triple helical structure is formed inside the
ER from combination of the alpha chains
• This determines the type of collagen fibre
produced viz:
• Type 1- two α1 and one α2 chain
Type 2- three α1 chains
• This is called procollagen
• Procollagen is transported into the golgi apparatus
• Here it is packaged and secreted by exocytosis
into the EC matrix
• Once outside the cell the registration peptides are
cleaved from the C and N termini forming
tropocollagen by action of procollagen peptidase

• Tropocollagen molecules gather to form collagen

fibrils via covalent cross linking by lysyl oxidase
• This links OHlysine and lysine residues.

• Multiple collagen fibrils form collagen fibres.

• Collagen are attached to cell membranes by

several types of protein including fibronectin
and integrin.