muscle contraction - seidler

Question 1

GSD V/ McArdle disease DM, s/s

Answer 1

• autosomal recessive disorder
• deficiency in muscle glycogen phosphorylase, rate limiting enzyme of glycogen degradation cleaving glucose residues from glycogen for release as glucose 1-phosphate
• suffer from fatigue, severe muscle cramping, myoglobinuria
• tolerate by reducing strenuous physical activity

Question 2

mutations in liver phosphorylase causes

Answer 2

Hers disesae (GSD VI)

Question 3

mutations in muscle phosphorylase causes

Answer 3

McArdle syndrome (GSD V)

Question 4

Duchenne muscular dystrophy (DMD)

Answer 4

X-linked recessive disorder
1 in 3500 incidence
- progressive muscle wasting, wheel chair by age 12, respiratory failure death within 10 years
-

Question 5

dystrophin

Answer 5

rod-like protein connecting cytoskeleton to basal lamina and stabilizing membranes and participating in calcium handling
partially absent in BMD, in frame mutation
completely absent in DMD, out of frame deletion

Question 6

milder form of DMD with later onset

Answer 6

Becker muscular dystrophy (BMD)

Question 7

cTn-I

Answer 7

cardiac muscle isoform of Tn-I, inhibitory, subunit of troponin
serum levels increase after myocardial infarction!

Question 8

sTn-I

Answer 8

has two forms

skeletal muscle isoform of Tn-I, inhibitory, subunit of troponin

Question 9

troponin subunits and importance

Answer 9

trimeric protein complex
- Tn-T tropomysin binding subunit; positions complex on filament
- Tn-C Calcium binding subunit; binds Ca2+ and relieves inhibition
- Tn-I inhibitory subunit; binds actin, inhibts myosin binding
Ca2+ binding changes proteins conformation, change transmitted to tropomyosin, allowing myosin to bind to actin filaments, resulting in muscle contraction

Question 10

area of just thin filaments/ actin

Answer 10

I band

Question 11

area of just thick filaments/ myosin

Answer 11

H zone

Question 12

extends entire length of thick filaments

Answer 12

A band

Question 13

disk off of which myosin chains coming ooff

Answer 13

M disk

Question 14

disk off of which thin filaments coming off

Answer 14

Z disk

Question 15

myosin head and tail

Answer 15

head region can hydrolyze ATP

self assembles at tails - bipolar assembly

Question 16

myosin is made up of

Answer 16

6 polypeptide chains (2 heavy chains; 4 light chains)
rod domain (helical)
two globular heads

Question 17

myosin heads are at ?? degree rotational symmetry

and surrounding thin filaments are at ??

Answer 17

myosin 30 degrees
thin filaments 60 degrees apart
so 6 thin filaments surrounding each actin 360 degrees circle

Question 18

in myosin structure, a and d are always positioned next to each other leading to

Answer 18

strong hydrophobic intreactions -> high structural integrity

Question 19

binding of ATP to myosin allows it to??

messed in what process??

Answer 19

• allows it to disengage thin filament

whats happening in rigormortis! no o2, atp

Question 20

how can a point mutation in myosin lead to a DOMINANT NEGATIVE mutation?

Answer 20

• one normal protein still being pumped out however A to D and D to A lining up of myosin messe dup leading to dominant illness
• so one bad copy messed you up

Question 21

each G acti nmonomer interacts with

Answer 21

4 neighbors

Question 22

mature actin filament contains

Answer 22

ADP bound to monomeric G-actin units

Question 23

caps the minus end (not at Z-disc) of thin filament preventing further polymerization

Answer 23

tropomodulin

Question 24

caps at plus end of thin filament

Answer 24

CapZ (or b-actinin, a heterodimer) associates with a-actinin

Question 25

"ruler" and template for actin polymerization

Answer 25

nebulin

Question 26

length of actin

Answer 26

1 mm ABSOLUTE | 180 repeats of 35 aa residues

Question 27

monomeric form of thin filament?? once polymerize??

Answer 27

G actin monomer | F actin polymerized

Question 28

at Z disc, what arranges actin in hexagonal bundle around myosin?

Answer 28

a-actinin!

Question 29

rope-ish protein tying z disc and thus myofibrils to one another, turns sarcomeres into "rib-like" costameres

Answer 29

desmin

Question 30

"ruler" for sarcomeres

Answer 30

titin

Question 31

titin is involve din

Answer 31

``` muscle ruler - sarcomere organization balances forces across sarcomere passive elasticity (after contraction, sarcomere needs to get back to rest, does it through titin) muscle signaling ```

Question 32

how does hypocalcemia lead to tetany when Ca+ is involved in muscle ocntraction?

Answer 32

Ca++ automatic inhibitor of VG Na+ channels - when Ca++ low, Na+ channel inhibition removed - mkaes it more responsive leading to spontaneous firing, get AP and muscle contractions

Question 33

mechanically inhibits ryanadine receptor; changes conformation and releases inhibition upon depolarization of cell

Answer 33

dihydropyridine receptor

Question 34

molecular events leading to smooth muscle contraction

Answer 34

Ca+ binds to calmodulin Ca++ - calmodulin complex binds to myosin light-chain kinase and both phosphorylate myosin with nonphosphorylated light chain to activate it

Question 35

chanes active site of muscle glycogen phosphorylase b to increase activity of enzyme leading to G6P, ATP formation

Answer 35

binding of AMP | phosphorlation by Ca++-calmodulin complex