Biochemistry of Muscle

Question 1

Muscle cells + Muscle Type

Answer 1

• Contract
• Actin and Myosin
• Sarcomere- unit of muscle from one Z line to the next. About 2.5um in
  length

1) Skeletal
- Striated due to sarcomeres
- Voluntary
- Each skeletal muscle fibre innervated by a motor neuron that
instructs it to contract
2) Cardiac
- Striated due to sarcomeres
- Involuntary
3) Smooth
- No sarcomeres
- Involuntary

Question 2

Thick Filament - Myosin

Answer 2

• Myosin has globular head and long tail
• Tails of 2 Myosins wind around each other
• Dimers of myosin bundled to form Thick filament
• Head of Myosin can bind two molecules: ATP and Actin
• Myosin head has enzyme activity ATPase
• In skeletal and cardiac muscle, Myosin ATPase activity is always on
• In smooth muscle, Myosin ATPase needs activation

Question 3

Thick Filament - Actin

Answer 3

• Filament organisation-two
  chains composed of actin monomers wound around
  each other
• Each Actin monomer has single Myosin Binding Site
  (MBS) on external surface covered by Tropomyosin
• Ca2
  + binds Troponin which moves Tropomyosin off
  the MBS of Actin
• Exposed MBS allows binding of myosin

Question 4

Sliding Filament Model of Muscle Contraction

Answer 4

1) Myosin high energy state allows head binds to Actin (cross-bridging)
2) ADP and Pi bound to Myosin head released. Same time, stored energy used to flex myosin head, (power stroke)pulling thin filament towards centre of sarcomere (M-line). Myosin head now low energy state
3) ATP binds Myosin head and allowing myosin to detach from actin
4) ATP hydrolysed to ADP and Pi. Energy transferred to Myosin- High Energy State

Ca2+ released from SR, unveils Myosin Binding Site on Actin. Myosin head binds to actin- cross-bridging. Start cycle again

Question 5

Skeletal Muscle Fibre

Answer 5

• responsible for the movement of the body
• Skeletal muscle contracts by excitation contraction
  coupling- AP induces Ca2+ release allowing contraction
  as long as ATP is available

4 types of fibres:
- Type 1, IIa, IIx, IIb

Slow fibres -contract slowly, generating low
levels of force. Use aerobic respiration to make ATP and
contract for long periods of time
Fast fibres - contract quickly, generating high levels of
force. Use anaerobic respiration to make ATP and
contract only for short periods of time

Question 6

Cardiac Muscle

Answer 6

• Mono or binucleated cells => Cell joined at intercalated discs, secured by
  desmosomes, Cells linked through Gap junction opening
• Action
  potential originates from sino-atrial (SA) node,
  spreads throughout heart through Gap junctions
• sympathetic nervous system increase SA
  firing through norepinephrine. Parasympathetic
  decreases SA firing
• epinephrine increases SA firing,
  hyperthyroidism induces tachycardia and
  hypothyroidism induces

Question 7

Cardiac Muscle Contraction

Answer 7

1) Action potential from SA node allows Extracellular[Ca2+]
to enter cell
2) Small amount of Extracellular Ca2+ entry sparks Ca2+
release from SR
3) Ca2+ binds troponin (as in skeletal muscle) allowing cross
bridging
4) Once AP stopped, one Ca2+ is exported for 3 Na+
imported through Na/Ca transporter
Cross bridging stops

Question 8

Smooth Muscle

Answer 8

• Found in blood vessels, lines organs

Contraction:
1) nervous system action potential to activate voltage operated Ca channel
2) binding of agonists to receptors
3) Nitric oxide
4) Elevated ca2+ levels
5) Ca2+ binds calmodulin leading to its activation Calmodulin activates Myosin light chain kinase (MLCK)Myosin in SM (called Myosin II) is inactive and needs to be phosphorylated to start ATP mediated cross bridging MLCK activates Myosin by phosphorylation

Question 9

ATP

Answer 9

1) Contraction
2) Move Ca2+ from cytosol back into SR
3) Re-establish Na+ and K+ gradients
allowing next Action potential to be
generated

Question 13

Sources of ATP

Answer 13

Breakdown of Creatine
Phosphate: CrP

Glycolysis: Glucose and
Glycogen

Oxidative phosphorylation:
Pyruvate, Fatty acids and
Amino Acids

Question 13

Oxygen Deficit

Answer 13

more oxygen used that can be delivered

Excess Post-Oxygen Consumption (EPOC) => difference between O2 used after exercise and level at rest

Rapid EPOC (high O2 use/ATP generation) => Resynthesis of PhosCreatine, Replenish muscle and blood O2

Slow EPOC (low O2 use/ATP generation) => Servicing increased metabolic rate; exercise increases all metabolic process, these use more energy than at rest. Driven mainly by epinephrine
Convert muscle lactic acid to pyruvic acid to glucose
Synthesize glycogen from glucose from muscle and circulation

Question 14

AMP

Answer 14

• ATP can also be generated without respiration by enzyme Adenylate
  kinase (AK)
• AK converts two molecules of ADP to generates ATP and AMP
• AMP levels are high when the energy levels of muscle are low

Question 15

IMP

Answer 15

AMP can can be converted to IMP (inosinic acid) by
AMP deaminase

Supports exercise by:
1) IMP generation liberates ammonia, which helps
prevent large decreases in cellular pH during exercise
2) . Ammonia also activates phosphofructokinase which
activates glycolysis- generates more energy

Question 16

AMP - Kinase

Answer 16

• Senses AMP
• Activated by exercise and high levels of AMP

Question 17

Creatine

Answer 17

• dipeptide made from glycine and arginine and methyl group from modified methionine (SAM)
• can be phosphorylated to form phosphocreatine (PCr) – Rapidly accessible energy store
• Phosphocreatine donates phosphate to ADP producing ATP
  (Creatine Kinase)

Question 18

Glycolysis

Answer 18

Glucose => ATP
- ATP produced 2.5x faster than Aerobic Resp
- No o2 use
- Rapid but but generates little energy per carbon atom (2)
Glucose- substrate for glycolysis cannot be stored
in cells- it would disturb osmotic pressure. stored as osmotically inert polymer - Glycogen

Question 19

Aerobic Respiration

Answer 19

• Glucose broken down to pyruvate before
  being used for aerobic respiration
• Slower process but 38 ATP per glucose, co2 and h20
• Energy source : AAs and FAs

Question 20

Glycogenolysis (Adv + Dis)

Answer 20

• Branched => - lots of points where it can be broken down
• Energy can be developed anaerobically

Glycogen is hydrous = absorbs water = energy to volume ratio is low,
(unlike fats).

Question 21

Glycogen Phosphorylase

Answer 21

Catalyses 1st step
1) Breaks glycogen to produce G-1-P
2) G-1-P converted by isomerase into G-6-P
3) G-6-P enters glycolysis

Liver GP => maintained in active form. Helps make glucose. Glucose is released into circulation to be used by other organs esp Brain and muscle esp during exercise.

Question 22

Muscle GP

Answer 22

Inactive Form
Isoenzymes
- GP-A = phosphorylated
- GP-B = unphosphorylated
GPB =(phosphorylase kinase)=> GPA
GPA =(phosphoprotein phosphatase)=> GPB

Relaxed state > Tense state

High energy decreases GP activity - When muscle has energy (High ATP or G-6-P) keep GP
activity low. Don’t breakdown glycogen

Low energy increases GP activity - When muscle has little energy (High AMP) GP activity
increased. Breakdown glycogen

Question 23

Fats as energy source

Answer 23

• High energy source
• Fatty acid molecules have more carbon atoms
• Fatty acid molecules have less oxygen and therefore can be oxidised more
  readily
• Fats stored mainly in adipose tissue (97%) and muscle (3%) as Triglycerides
• tored adipose triglycerides converted to Free Fatty Acid (FFA) by exercise
  induced Epinephrine that ultimately activates hormone sensitive lipase

Question 24

FFA generation

Answer 24

1)FFA entry into muscle cells - CD36
2) Activation of FFA in cytosol - Activation is a two step
process resulting in FAA attached to AcylCoA. ATP essential
for 1st step
3) Transport of activated fatty acid into mitochondria - CoA removed replaced with Carnitine => Acylcarnine, Carnitine moved out of matrix by Translocase transporter
as Acylcarnitine come in
4) β-oxidation in mitochondrial matrix - sequentially removes 2 carbons as Acetyl-CoA

Question 25

Muscle Protein Metabolism

Answer 25

• Amino acids stored as contractile proteins in skeletal muscle
• Muscle proteins and organelles broken down to amino acids by Proteosomes and Autophagy

Question 26

Fatigue

Answer 26

Exercise induced reduction in power generating capacity of muscle
- Muscle become less responsive to brain stimuli
Lactic Acid

Question 27

Cori Cycle

Answer 27

Managing muscle Lactic acid and maintaining glucose

Slow twitch fibres do not fatigue easily
Lactate does not induce fatigue

Question 28

Longer term adaptations to differing exercise regimes

Answer 28

Endurance Training = results in gene expressions
changes that promote mitochondria biogenesis and
blood vessel formation- support aerobic respiration
- induces PGC-1α1 isoform which supports increase specific protein synthesis ofmitochondrial proteins, angiogenic factors and MHC I and MHC IIa. Muscle fibres are small, full ofmitochondria and contract slowly

Resistance Training = induces genes that support
increased protein synthesis esp contractile proteins,
increases muscle mass
- induces transcription of PGC-1α4 isoform which supports increase inglobal proteinsynthesis and expression of MHC IIx and MHC IIB. Muscle fibres become bigger and faster contracting

Greatest elevation of protein synthesis occurs within
an hour following workout- greatest benefit of
protein supplements after exercise

BCAAs = activate protein
synthesis pathways