Contractile Proteins

Question 1

McArdle disease

Answer 1

a deficiency in in the muscle form of glycogen phosphorylase

Question 2

Patients with McArdle disease are unable to supply what to muscles?

Answer 2

Glucose

Question 3

Patients with McArdle disease suffer what?

Answer 3

fatigue, severe muscle cramping, and muscle breakdown. Myoglobin occurs in urine during intense exercise. Patients tolerate disease by decreasing strenuous physical activity.

Question 4

Where are liver and muscle glycogen phosphorylase genes located?

Answer 4

Liver and muscle isoforms of phosphorylase are products of separate genes located on chromosomes 14 and 11, respectively

Question 5

Liver glycogen phosphorylase mutations cause:

Answer 5

Liver isoform mutations cause Hers disease (GSD VI)

Question 6

Muscle glycogen phosphorylase mutations cause

Answer 6

Muscle isoform mutations cause McArdle syndrome (GSD V)

Question 7

Both muscle and liver glycogen phosphorylase are activated by:

Answer 7

PhK (phosphorylase kinase)

Question 8

Both muscle and liver glycogen phosphorylase are inactivated by:

Answer 8

ATP and Glucose 6-phosphate

Question 9

Muscle glycogen phosphorylase is activated by:

Answer 9

PhK, AMP, Ca2+ calmodulin complex and G-actin, Ca2+

Question 10

LIver glycogen phosphorylase is inactivated by:

Answer 10

free glucose. Is not affected by AMP

Question 11

Brain glycogen phosphorylase lacks a phosphorylation site for what?

Answer 11

PhK, but is responsive to AMP

Question 12

Ca2+ - calmodulin is further capable of activating what?

Answer 12

Phosphorylase - alpha

Question 13

Phsophorylase - alpha does what?

Answer 13

Degrades glycogen to produce ultimately produce ATP

Question 14

What is Dantrolene?

Answer 14

A muscle relaxant that binds to ryanodine receptors

Question 15

What does Dantrolene prevent?

Answer 15

Mobilization of Ca2+ and subsequent activation of phosphorylase alpha

Question 16

Dantrolene is used to treat what?

Answer 16

Malignant hyperthermia caused by anesthesia in susceptible patients

Question 17

Malignant hyperthermia is enhanced by mutations in what two proteins?

Answer 17

Ryanodine receptors or L-type voltage-gated Ca2+ channels

Question 18

What is malignant hyperthermia caused by?

Answer 18

Reabsorption of mobilized Ca2+, which requires larges amounts of ATP

Question 19

Myosin is a superfamily consisting of:

Answer 19

class II, two-headed myosins that form filaments.

Question 20

Myosin is found in:

Answer 20

striated muscle, smooth muscle and non-muscle cells

Question 21

Myosin is described as a ______ protein

Answer 21

hexameric

Question 22

Myosin consists of:

Answer 22

two myosin heavy chain (MyHC) subunits and two pairs of non-identical light chain subunits

Question 23

Myosin globular head domain binds:

Answer 23

actin and ATP (required for motor activity)

Question 24

Myosin rod domain is:

Answer 24

near alpha-coiled and assembles into thick filaments of sacromeres

Question 25

MyHC isoforms

Answer 25

MyHC I, MyHC IIa, MyHCIIx

Question 26

MyHC I

Answer 26

slow, Type I muscle fibers and heart ventricles

Question 27

MyHC IIa

Answer 27

fast, Type IIa fibers

Question 28

MyHCIIx

Answer 28

fast, Type IIB fibers

Question 29

Dermatomyositis

Answer 29

disappearance of myosin and other proteins with thick filaments

Question 30

Dermatomyositis is frequently triggered by:

Answer 30

systemic corticosteroid hormone treatment, postsynaptic block of neuromuscular transmission and prolonged mechanical ventilation

Question 31

Dystrophin is a:

Answer 31

rod shaped cytoplasmic protein

Question 32

Dystrophin does what?

Answer 32

Connects cytoskeleton of a muscle fiber to the surrounding ECM through the cell membrane

Question 33

Dystrophin stabilizes what?

Answer 33

Stabilizes the sarcolemma against mechanical forces experience during muscle contraction or stretch – a molecular shock absorber

Question 34

Dystrophin is part of what complex?

Answer 34

costamere or dystrophin-associated protein complex

Question 35

Duchenne muscular dystrophy

Answer 35

X linked, recessive disorder with incidence of 1 in 3500 boys and leads to progressive muscle wasting

Question 36

Becker muscular dystrophy

Answer 36

milder than DMD with later onset

Question 37

Duchenne and Becker muscular dystrophy are both due to:

Answer 37

mutations in dystrophin gene which codes for dystrophin

Question 38

Becker muscular dystrophy is

Answer 38

in frame mutation - produces smaller dystrophin proteins

Question 39

Duchenne muscular dystrophy is

Answer 39

Out-of-frame and results in little to no dystrophin expression

Question 40

Desmin

Answer 40

muscle specific, type III intermediate filament that integrates the sarcolemma, Z disk and nuclear membrane in sarcomeres and regulates sarcomere architecture

Question 41

High Ca2+ levels cause ____ in skeletal muscle

Answer 41

Contraction

Question 42

Low Ca2+ levels cause ____ in skeletal muscle

Answer 42

relaxation

Question 43

Troponin is

Answer 43

a trimeric protein complex that plays role in muscle contraction and relaxation triggered by elevated or depressed levels of intracellular Ca2+.

Question 44

Subunits of troponin:

Answer 44

tropomysin-binding subunit (Tn-T), calcium-binding subunit (Tn-C) and the inhibitory subunit (Tn-I).

Question 45

Describe sequence of events following calcium binding to troponin

Answer 45

When calcium binds, the protein changes conformation, which is transmitted to tropomysin, which allows myosin to bind the actin filaments, enabling muscle contraction.

Question 46

Tn-I subunit comes in three isoforms

Answer 46

cTn-I: in cardiac muscle. Serum levels increase after myocardial infarction sTn-I: in skeletal muscle (two isoforms of this)

Question 47

MLCK/calmodulin is what kind of protein

Answer 47

Myosin light-chain kinase is a serine/threonine specific protein kinase that phosphorylates the regulatory chain of myosin II

Question 48

MLCK/calmodulin is a muscle contraction alternative to troponin found in what kind of muscle

Answer 48

smooth muscle

Question 49

MLCK is activated via:

Answer 49

Calcium binding to calmodulin in smooth muscle

Question 50

Activated MLCK ______ myosin light chain causing a _______ change

Answer 50

phosphorylates/conformational

Question 51

Contraction in smooth muscle occurs following myosin _____ binding to the _____ filament

Answer 51

cross bridge/actin

Question 52

How is smooth muscle contraction terminated?

Answer 52

Only by dephosphorylating the myosin light chain (this is due to the induced conformational change)

Question 53

How many poles does the myosin assembly have?

Answer 53

Two - it is bipolar

Question 54

Myosin (head region) does what to ATP?

Answer 54

Hydrolyzes it

Question 55

What is the P-loop?

Answer 55

It is the location of the ATPase domain within the S1 region of the myosin globular head region

Question 56

Thin filaments are

Answer 56

Actin

Question 57

G-actin --> what?

Answer 57

F-actin

Question 58

Nebulin is

Answer 58

a 1mm long template for the length of actin polymerization

Question 59

Tropomyosin is

Answer 59

wrapped around actin filaments and blocks the myosin binding sites

Question 60

Titin is

Answer 60

involved in sarcomere organization. Balances the forces across sarcomere. Assists in passive elasticity and muscle signaling

Question 61

The myosin binding site is exposed by:

Answer 61

calcium binding troponin complex (at site C) and inducing movement of tropomyosin out of the fucking way

Question 62

Glycogen phosphorylase is an _____ enzyme

Answer 62

allosteric (for AMP)