Download 45_Biochemistry of Muscles

MUSCLES
•40-45 % of
body mass
•only system
converting
chemical
energy into
mechanical
2 types
-skeletal
(striated)
-smooth
Structural
unit muscle fiber
(myocyte)
Contains
many nuclei
located along
the cell
Muscle
structure
Muscle
structure
Types of Muscle
Skeletal Muscle Organization
A single muscle fiber
Chemical composition of
skeletal muscles
Proteins of muscles
3 types:
•proteins of
sarcoplasma
•proteins of
miofibrils
•proteins of
stroma
ACTIN & THIN
FILAMENTS
G-actin is the monomer
which will form the thin
filament. It is a protein
with a molecular weight of
43,000. It has a prominent
site for cross-linkage with
myosin.
G-actin
↓
F-actin
(6-7 nm long polymerized
G-actin, double stranded
in structure)
↓
Thin filaments
PROTEINS OF MUSCLE:
Proteins of Sarcoplasma
•Miogen fraction
(enzymes of glycolysis
etc.)
•Albumins
•Globulins
•Myoglobin
(chromoprotein,
provides the red color
to muscles, responsible
for oxygen storage)
Proteins of Stroma
•collagen
•keratin
•elastin
are constituents of
connective tissue of
vessel walls, nerves,
sarcolema.
Proteins of Miofibrils
•Myosin (56-60 %)
•Actin (20-25 %)
•Tropomyosin (10-15 %)
•Troponin complex (4-6 %)
Regulatory Proteins of the Muscles
TROPOMYOSIN
TROPONIN
• Rod-like protein
• Mol. Weight: 70,000
• 2 chains: alpha & beta
chains
• Under resting conditions, it
covers the site for myosin
attachment on F-actin
molecule.
• Forms part of Thin filaments
• Globular protein complex
made of 3 polypeptides
• Forms part of thin filaments
Binds to Ca2+
Inhibitory in function
Attached to Tropomyosin
Structure of filaments and myofibrils
Sarcoplasma of
striated muscle
fibers contains
myofibrils
oriented along
which are built
of 2 types
protein
filaments: thick
and thin
•Muscle contraction is carried out due to the
sliding of thick and thin filaments
•Chemical energy – ATP hydrolysis
•Contraction is regulated by Ca2+ concentration
Structure of Thick Filament
•Thick filaments consist of myosin molecules
•Myosin molecule built of 2 heavy (200000 Da)
and 4 light (16000-25000 Da) chains
•Heavy chains are coiled around each other and
form the “tail” of the molecule
•2 light chains form the globular head of the
molecule
•The head has ATP-ase properties
About 400 molecules of myosin are
combined in the thick filament
About half of molecules is directed
to one end of filament, another half
– to another end
Structure of Thin Filament
Three proteins: actin, tropomyosin, troponin
Two forms of actin: globular G-actin and fibril F-actin
Molecules of globular actin are joined to form F-actin
Two chains of F-actin are coiled in spiral
In the groove of spiral of F-actin tropomiosin is located
One molecule of tropomiosine contacts with 7 pairs of
G-actin
1 molecule of troponin drops on 1 molecule of tropomiosin
There are three subunits of troponin
Miofibrils contain about 2500
filaments
There are 6 thin filaments for 1 thick
filament
•Structural unit of miofibril sarcomer
•Both ends of thick miosin filaments are free
•One end of thin filaments is attached to Z-plate
BIOMECHANISM OF MUSCLE
CONTRACTION
•Potential spreads along
miofiber
•Signal is transferred to
cisterna of endoplasmic
reticulum
•Permeability of membranes
for Ca2+ ions is changed and
they get out into sarcoplasma
•During the rest
concentration of Ca2+ in
sarcoplasma is less than 10-7
mol/L
•After Ca2+ exit from
cisternas the concentration
reaches 10-5 mol/L
•Ca2+ binds to Ca-binding subunit of troponin
•Conformation of protein is changed
•Molecule of
tropomiosin
moves along
groove of thin
filament
• As result
centers for
connection with
heads of myosin
are opened on
the molecules of
G-actin
•Myosin heads combined with ATP bind to
the closest molecules of G-actin
•ATPase center is activated and ATP is
hydrolized
•Head bent
•Sliding of thin filament along myosin
•New ATP molecule binds to head of
myosin
•Bridge is torn
•In the condition of Ca presence the
head binds to the next actin molecule
•Frequency - 50 times/s
•Heads works not synchronously
•Nervous impulses stop to come
•Ca-ATPase transfers Ca2+ from
sarcoplasma into cisternas
•Complex Ca2+-troponin is dissotiated
•Tropomiosin moves
•Molecules of actin are blocked
•Bridges are torn
•Muscle relaxation
•ATP is required
both for contraction
and relaxation of
muscles
•In ATP deficiency
the bridges between
actin and myosin are
not torn
•Filaments are fixed
in connected state –
muscle contraction
(cadaver rigidity)
SOURSES OF ENERGY FOR MUSCLE
WORK
•ATP (5 umol for 1 g of
tissue) – enough for 2-3
s
•Kreatinphosphate – till
10 s
•Glycolysis
•Oxidative
phosphorylation
RED AND WHITE MUSCLES
Res fibers
•Lot of myoglobin and mitochondria
•Oxidative phosphorylation is active
•Are contracted slowly, for a long time, no
tiredness for long time
White fibers
•Little hemoglobin and mitochondria
•More glycogen
•Glycolisis is specific
•Are contracted fast, fast tiredness
Summary of major features of the biochemistry of
skeletal muscle related to its metabolism
• Skeletal muscle functions under both aerobic (resting) and anaerobic
(eg, sprinting) conditions, so both aerobic and anaerobic glycolysis
operate, depending on conditions.
• Skeletal muscle contains myoglobin as a reservoir of oxygen.
• Skeletal muscle contains different types of fibers primarily suited to
anaerobic (fast twitch fibers) or aerobic (slow twitch fibers) conditions.
• Actin, myosin, tropomyosin, troponin complex (TpT, Tpl, and TpC),
ATP, and Ca2+ are key constituents in relation to contraction.
• The Ca2+ ATPase, the Ca2+ release channel, and calsequestrin
are proteins involved in various aspects of Ca2+ metabolism in
muscle.
Summary of major features of the biochemistry of
skeletal muscle related to its metabolism
• Insulin acts on skeletal muscle to increase uptake of glucose.
• In the fed state, most glucose is used to synthesize glycogen,
which acts as a store of glucose for use in exercise; “preloading”
with glucose is used by some long-distance athletes to build up
stores of glycogen.
• Epinephrine stimulates glycogenolysis in skeletal muscle, whereas
glucagon does not because of absence of its receptors.
• Skeletal muscle cannot contribute directly to blood glucose
because it does not contain glucose-6-phosphatase.
• Lactate produced by anaerobic metabolism in skeletal muscle
passes to liver, which uses it to synthesize glucose, which can then
return to muscle (the Cori cycle).
Summary of major features of the biochemistry of
skeletal muscle related to its metabolism
• Skeletal muscle contains phosphocreatine, which acts as an energy store
for short-term (seconds) demands.
• Free fatty acids in plasma are a major source of energy, particularly
under marathon conditions and in prolonged starvation.
• Skeletal muscle can utilize ketone bodies during starvation.
• Skeletal muscle is the principal site of metabolism of branched-chain
amino acids, which are used as an energy source.
• Proteolysis of muscle during starvation supplies amino acids for
gluconeogenesis.
• Major amino acids emanating from muscle are alanine (destined
mainly for gluconeogenesis in liver and forming part of the glucose-alanine
cycle) and glutamine (destined mainly for the gut and kidneys).