Structure of Muscle and Enzymology Flashcards
What percentage of muscle is skeletal?
30-40
What is the function of skeletal muscle?
Attached to bones to provide posture and movement
Contributes to temperature control
What is the organisation of muscle filaments?
myofibril
Fibre
fasicule/bundle
muscle
What/where are the connective tissue layers?
Endomysium around fibres
Perimysium around bundles
Epimysium around muscle
Which level of muscle organisation contains blood vessels?
Bundles
What is the structure of fibres?
Multinucleate cells with 1 nucleus per 30µm
10-100µm diameter
What diameter are myofibrils?
1-3µm
What length is overall muscle?
> 300mm
What length is the sarcomere?
2-3µm
What is the ratio of M:A in a sarcomere?
2:1
How many myosin types are there?
12 classes
38 genes
What is the main myosin in contraction?
2
What is the structure of the myosir filaments?
Antiparallel myosin proteins
- 3nm axial repeat
- 9 helical repeat
What is the structure of a myosin dimer?
N terminal head
4 Light chains
155nm coiled heavy chain tail
What does titin bind?
Links myosin tail to Z disc
Spans half of sarcomere
What function does Titin have?
Provides 90-95% of elastic/passive force
What is the structure of a myosin head?
NBD U50 actin/cardiomyopathy loop L50 Relay helix with kink converter α helix lever arm regulatory and essential light chains
What is the structure of the actin filament?
Left helix
72nm pitch
5.5nm G-actin subunit repeat
4-7nm diameter
Where does the actin anchor to?
+ /fast growing end
α-actinin in Z disc
What does nebulin do?
Binds actin to regulate filament length
How frequently does tropomyosin bind to actin?
1 per 7 actin subunits
What is the troponin complex that binds Calcium?
TnC
Is all troponin calcium binding equal?
No! Different isoforms
What does tropomyosin do?
Binds in F-actin grooves to occlude the binding site f the myosin head
What is the structure of the the troponin-tropomyosin complex?
Actin TnI TnC TnT Tropomysoin
Outline the excitation contraction coupling?
Impulse arrives at motor end plate and passes across the synapse to the sarcolemma
Diffuses to T tubule to span into myofibrils
Conformational change in v-gated Dihydropyridine receptor transducted to RyR ER Calcium channel
Ca released into myofibrillar space to [10µM]
Ca binds to TonC
Conformational change removes tropomyosin
Myosin binds
How is the ER calcium store maintained?
Calsequestrin buffer proteins
SERCA ATPase pump
Is the cross bridge response immediate?
No, delay for exposure of binding sites
Is the cross bridge response uniform?
No, more binding sites exposed with [Ca]
What are the 3 types of fasicules?
parallel
unipinnate
bipinnate
What characteristics do parallel fasicules have?
Faster
greater range
What characteristics do pinnate fasicules have?
Larger area
Stronger
What is the equation for force?
F=(Vσ)/length
Where are tendons in bipinnate muscles?
Intramuscular
How fast is ATP hydrolysis in muscle?
10^9 faster than normal
How many ATP are hydrolysed per second?
4
What is Mg needed for in muscle?
Coordination of 4 Water and Phosphates of ATP
What is the structure of the ATP binding site in myosin?
P loop locks ATP in the active site
S/T residues coordinate H2O
How does ATP hydrolysis prime myosin to bind to actin?
Relaxes the P loop
By rotation of myosin
Allows stronger binding of actin to the cardiomyopathy loop upon tropomyosin removal
What phase of the cross bridge cycle has a straight relay helix?
Actin-Myosin
What drives the powerstroke?
Release of phosphate
What distance does the myosin head move in the power stroke?
12nm
How does ATP binding act in the cross bridge cycle?
Closure of P loop
Bends relay helix
Induces stress in conformation (high energy state)
When does ATP hydrolysis occur in the cross bridge cycle?
When detached
What form is most myosin in the cross bridge cycle?
ATP/ADP+Pi bound
Detached from actin
What stage of the actin-myosin cycle has tightest binding?
Straight relay helix of A.M
How many actin subunits bind per myosin head?
5
What residues control the relay helix kink?
Hydrophobic
How much energy does ATP hydrolysis provide?
-60kJ/mol
How much force does 1 Joule provide?
1N/m
How efficient is myosin ATPase?
60%