Contractile Proteins Flashcards
McArdle disease
a deficiency in in the muscle form of glycogen phosphorylase
Patients with McArdle disease are unable to supply what to muscles?
Glucose
Patients with McArdle disease suffer what?
fatigue, severe muscle cramping, and muscle breakdown. Myoglobin occurs in urine during intense exercise. Patients tolerate disease by decreasing strenuous physical activity.
Where are liver and muscle glycogen phosphorylase genes located?
Liver and muscle isoforms of phosphorylase are products of separate genes located on chromosomes 14 and 11, respectively
Liver glycogen phosphorylase mutations cause:
Liver isoform mutations cause Hers disease (GSD VI)
Muscle glycogen phosphorylase mutations cause
Muscle isoform mutations cause McArdle syndrome (GSD V)
Both muscle and liver glycogen phosphorylase are activated by:
PhK (phosphorylase kinase)
Both muscle and liver glycogen phosphorylase are inactivated by:
ATP and Glucose 6-phosphate
Muscle glycogen phosphorylase is activated by:
PhK, AMP, Ca2+ calmodulin complex and G-actin, Ca2+
LIver glycogen phosphorylase is inactivated by:
free glucose. Is not affected by AMP
Brain glycogen phosphorylase lacks a phosphorylation site for what?
PhK, but is responsive to AMP
Ca2+ - calmodulin is further capable of activating what?
Phosphorylase - alpha
Phsophorylase - alpha does what?
Degrades glycogen to produce ultimately produce ATP
What is Dantrolene?
A muscle relaxant that binds to ryanodine receptors
What does Dantrolene prevent?
Mobilization of Ca2+ and subsequent activation of phosphorylase alpha
Dantrolene is used to treat what?
Malignant hyperthermia caused by anesthesia in susceptible patients
Malignant hyperthermia is enhanced by mutations in what two proteins?
Ryanodine receptors or L-type voltage-gated Ca2+ channels
What is malignant hyperthermia caused by?
Reabsorption of mobilized Ca2+, which requires larges amounts of ATP
Myosin is a superfamily consisting of:
class II, two-headed myosins that form filaments.
Myosin is found in:
striated muscle, smooth muscle and non-muscle cells
Myosin is described as a ______ protein
hexameric
Myosin consists of:
two myosin heavy chain (MyHC) subunits and two pairs of non-identical light chain subunits
Myosin globular head domain binds:
actin and ATP (required for motor activity)
Myosin rod domain is:
near alpha-coiled and assembles into thick filaments of sacromeres
MyHC isoforms
MyHC I, MyHC IIa, MyHCIIx
MyHC I
slow, Type I muscle fibers and heart ventricles
MyHC IIa
fast, Type IIa fibers
MyHCIIx
fast, Type IIB fibers
Dermatomyositis
disappearance of myosin and other proteins with thick filaments
Dermatomyositis is frequently triggered by:
systemic corticosteroid hormone treatment, postsynaptic block of neuromuscular transmission and prolonged mechanical ventilation
Dystrophin is a:
rod shaped cytoplasmic protein
Dystrophin does what?
Connects cytoskeleton of a muscle fiber to the surrounding ECM through the cell membrane
Dystrophin stabilizes what?
Stabilizes the sarcolemma against mechanical forces experience during muscle contraction or stretch – a molecular shock absorber
Dystrophin is part of what complex?
costamere or dystrophin-associated protein complex
Duchenne muscular dystrophy
X linked, recessive disorder with incidence of 1 in 3500 boys and leads to progressive muscle wasting
Becker muscular dystrophy
milder than DMD with later onset
Duchenne and Becker muscular dystrophy are both due to:
mutations in dystrophin gene which codes for dystrophin
Becker muscular dystrophy is
in frame mutation - produces smaller dystrophin proteins
Duchenne muscular dystrophy is
Out-of-frame and results in little to no dystrophin expression
Desmin
muscle specific, type III intermediate filament that integrates the sarcolemma, Z disk and nuclear membrane in sarcomeres and regulates sarcomere architecture
High Ca2+ levels cause ____ in skeletal muscle
Contraction
Low Ca2+ levels cause ____ in skeletal muscle
relaxation
Troponin is
a trimeric protein complex that plays role in muscle contraction and relaxation triggered by elevated or depressed levels of intracellular Ca2+.
Subunits of troponin:
tropomysin-binding subunit (Tn-T), calcium-binding subunit (Tn-C) and the inhibitory subunit (Tn-I).
Describe sequence of events following calcium binding to troponin
When calcium binds, the protein changes conformation, which is transmitted to tropomysin, which allows myosin to bind the actin filaments, enabling muscle contraction.
Tn-I subunit comes in three isoforms
cTn-I: in cardiac muscle. Serum levels increase after myocardial infarction
sTn-I: in skeletal muscle (two isoforms of this)
MLCK/calmodulin is what kind of protein
Myosin light-chain kinase is a serine/threonine specific protein kinase that phosphorylates the regulatory chain of myosin II
MLCK/calmodulin is a muscle contraction alternative to troponin found in what kind of muscle
smooth muscle
MLCK is activated via:
Calcium binding to calmodulin in smooth muscle
Activated MLCK ______ myosin light chain causing a _______ change
phosphorylates/conformational
Contraction in smooth muscle occurs following myosin _____ binding to the _____ filament
cross bridge/actin
How is smooth muscle contraction terminated?
Only by dephosphorylating the myosin light chain (this is due to the induced conformational change)
How many poles does the myosin assembly have?
Two - it is bipolar
Myosin (head region) does what to ATP?
Hydrolyzes it
What is the P-loop?
It is the location of the ATPase domain within the S1 region of the myosin globular head region
Thin filaments are
Actin
G-actin –> what?
F-actin
Nebulin is
a 1mm long template for the length of actin polymerization
Tropomyosin is
wrapped around actin filaments and blocks the myosin binding sites
Titin is
involved in sarcomere organization. Balances the forces across sarcomere. Assists in passive elasticity and muscle signaling
The myosin binding site is exposed by:
calcium binding troponin complex (at site C) and inducing movement of tropomyosin out of the fucking way
Glycogen phosphorylase is an _____ enzyme
allosteric (for AMP)
