BCHE4090

Biochemistry for
Sport and Exercise
 Biochemistry of
skeletomuscular tissues
 Textbooks

Pages 192-199; Pages 100-101;

338-349; 356; 153-162;
 Contents in brief
1) The sliding filament mechanism
2) The neuromuscular junction
3) Control of muscle tension
4) Motor units and twitch contraction
5) Frequency of stimulation
6) Exercise and skeletal muscle tissue
7) Skeletal-articular tissue turnover
8) Molecular pathways for skeletal muscle hypertrophy
The sliding filament mechanism
The sliding filament mechanism
 Muscle contraction
 Myosin heads attach to + slide along the thin filaments
 Consumption of ATP
The sliding filament mechanism
2
 The contraction cycle
 ATP hydrolysis
Myosin head includes ATP-binding site + ATPase
ATPase hydrolyze ATP
 Myosin head activated + reoriented

(Tortora & Derrickson 2006)

The sliding filament mechanism
3
 The contraction cycle
 Attachment of myosin to actin to form cross-
bridges
 ATP hydrolysis activates
myosin head
 Activated myosin head
attaches to myosin-binding
site on actin

(Tortora & Derrickson 2006)

The sliding filament mechanism
4
 The contraction cycle
 Power stroke
Occur after cross-bridge formation
Force generated
Slide thin filament towards the M line

(Tortora & Derrickson 2006)

The sliding filament mechanism
5
 The contraction cycle
 Detachment of myosin from actin
At the end of power stroke, ATP binds to myosin
head
 Myosin head detaches
from actin
 Return to Step : ATP
hydrolysis

(Tortora & Derrickson 2006)

 Summary

Invest ATP on myosin head

Cross bridge formation

Powered movement
The sliding filament mechanism
6
 Excitation-contraction coupling
 Storage Ca2+ of in sarcoplasmic reticulum (SR)
 Muscle action potential opens SR Ca2+ release
channels
 Ca2+ flows into sarcoplasm
 Ca2+  contraction
 Ca2+ transported back to SR by Ca2+ active transport
pump

 Length-tension relationship
 Force generated by muscle
contraction related to length
of sarcomere
The sliding filament mechanism

7
Length-tension relationship
 Force generated by muscle contraction related to
length of sarcomere
 Too short/too
long: weak
 Between short
and long: strong
The neuromuscular junction
(NMJ)
The neuromuscular junction
(NMJ)
 The synapse between somatic motor
neuron and skeletal muscle fibre
 NMJ 2
 Action potential at axonal terminal
① Release acetylcholine (ACh)
② Activation of ACh receptors
③ Production of muscle action potential
④ Termination of ACh activity

(Cecilia Phillips; Tortora & Derrickson 2006)

 NMJ 3
① Release acetylcholine
(ACh)
 Voltage-gated channel
opened
 Ca2+ flow into the neuron
 Synaptic vesicles undergo
exocytosis of ACh
 Enough ACh activates to
ACh receptors on muscle
fibre

(Tortora & Derrickson 2006)

 NMJ 4
② Activation of ACh receptors
 Ligand(ACh)-gated channel in muscle fibre opened
 Small cations, eg. Na+ flow into the fibre
 Accumulation of positive charge inside fibre
 Muscle action potential generated

(Tortora & Derrickson 2006)

 NMJ 5
③ Production of muscle
action potential
 Muscle action potential
spread along muscle fibre
(transverse tubules)
 Stored Ca2+ in SR released
 Contraction cycle initiated

(Tortora & Derrickson 2006)

 ④ Termination of ACh activity NMJ 6
 Acetylcholine esterase (AChE) present around synaptic
cleft
 ACh rapidly broken down by AChE
 Short effect of ACh-receptor binding
 Muscle action potential reduced
 Ca2+ channel in SR closed
 Troponin-tropomyosin of thin filament back to resting
position
 Contraction cycle terminated

(Tortora & Derrickson 2006)

 Summary 2

Neuronal action potential

ACh release to synaptic cleft

ACh esterase
Muscle fibres activated
 Summary 3

ACh-gated channel

Active transport of Na+

Muscle fibre Na+ influx

Muscle action potential

 Summary 4

Muscle action potential

Ca2+ channel closed

Ca2+ release from SR

Muscle contraction
Muscle regulation
 Control of muscle tension
 One action potential  one muscle potential

  frequency of action potential   force of

muscle contraction

(Tortora & Derrickson 2010)

 Twitch contraction
 Twitch contraction
 ~2 msec latent period:
 Spread of muscle potential
 Ca2+ release from SR

 10-100 msec contraction period:

 Ca2+ binds to troponin
 Actin exposed to myosin
 Cross-bridge formed

(Tortora & Derrickson 2010)

 Twitch contraction 2
 Twitch contraction
 10-100 msec relaxation period
 Ca2+ transported back to SR
 Myosin-binding site of actin covered by
tropomyosin
 Myosin detached from actin

 5 msec refractory period

 When 1 action potential applied immediately after
another
 Muscle fibre responds to the first NOT second
 Fibre temporarily loses excitability
(Tortora & Derrickson 2010)
 Exercise and skeletal muscle
tissue
 Various types of exercise induce changes in
skeletal muscle fibres
 Endurance-type exercises
 Fast glycolytic transformed to oxidative-glycolytic
fibres
  mitochondria number, blood supply, etc

 Exercises for strength

  synthesis of actin and myosin
  fast glycolytic fibre size and strength
Bone modelling and remodelling
Skeletal-articular tissue turnover
 Bone
 Most dynamic skeletal-articular tissue:
 Turnover ~3 years

 Bone turnover occurs through

 Modeling
 Remodeling

 Osteoblasts and osteoclasts work

independently on
 Periosteal surface (outer surface)
 Endocortical surface (inner surface bordering
marrow cavity)
Skeletal-articular tissue turnover
2
 Modeling
 Cellular activation  bone formation/resorption 
changes in size/shape of bones
 Common during growth

 Remodeling
 Local process:
 Osteoclasts activated  resorb bone
 Osteoblasts activated  fill up the cavity with
new organic matrix and minerals
Summary 5

(Kyoto University)
 Molecular pathways for
skeletal muscle hypertrophy
 Molecular pathways for
skeletal muscle hypertrophy
 Overview
 Mechanical overload (MOV)  activation of
numerous signals
 Responses include
①  electrical activation (Ca2+)
② Autocrine signals, eg. IGF-1, prostaglandins, etc
③ Acute immune response, eg cytokine secretion
④  enzymes, eg. glycolytic enzymes, etc
⑤ Activation of signaling cascades
⑥ Activation of satellite cells to generate muscle
fibres
 Molecular pathways for
skeletal muscle hypertrophy 2
 Molecular pathways
 Calcineurin (CaN) pathway
 Calcium-calmodulin protein kinase (CaMK)
pathway
 Insulin-like growth factor (IGF)-1 pathway
Molecular pathways for skeletal
muscle hypertrophy 3
 Calcineurin (Cn or CaN) pathway
 Ca2+  Cn and calmodulin (CaM) interaction  Cn
activation
 Activated Cn  nuclear
factor of activated T-cell
(NFAT)
dephosphorylation
 Activated Cn 
myocyte enhancer
factor (MEF) 2
dephosphorylation or
interaction with NFAT
 Transcriptional events
 muscle hypertrophy (nature.com)
Molecular pathways for skeletal
muscle hypertrophy 3
 Calcineurin (Cn) pathway
 Ca2+  CaN and calmodulin (CaM) interaction 
CaN activation
 Activated CaN 
nuclear factor of
activated T-cell (NFAT)
dephosphorylation
Cn
 Activated CaN 
myocyte enhancer
factor (MEF) 2
dephosphorylation or
interaction with NFAT
 Transcriptional events
 muscle hypertrophy (nature.com)
Molecular pathways for skeletal
muscle hypertrophy 3
 Calcineurin (CaN) pathway
 Ca2+  CaN and calmodulin interaction  CaN
activation
 Activated CaN 
nuclear factor of
activated T-cell (NFAT)
dephosphorylation
 Activated CaN 
myocyte enhancer
factor (MEF) 2
dephosphorylation or
interaction with NFAT
 Transcriptional events
 muscle hypertrophy (nature.com)
Molecular pathways for skeletal
muscle hypertrophy 3
 Calcineurin (CaN) pathway
 Ca2+  CaN and calmodulin interaction  CaN
activation
 Activated CaN 
nuclear factor of
activated T-cell (NFAT)
dephosphorylation
 Activated Cn 
myocyte enhancer
factor (MEF) 2
dephosphorylation or
interaction with NFAT
 Transcriptional events
 muscle hypertrophy (nature.com)
Molecular pathways for skeletal
muscle hypertrophy 3
 Calcineurin (CaN) pathway
 Ca2+  CaN and calmodulin interaction  CaN
activation
 Activated CaN 
nuclear factor of
activated T-cell (NFAT)
dephosphorylation
 Activated CaN 
myocyte enhancer
factor (MEF) 2
dephosphorylation or
interaction with NFAT
 Transcriptional events
 muscle hypertrophy (nature.com)
 Molecular pathways for
skeletal muscle hypertrophy 4
 Calcium-calmodulin protein kinase (CaMK)
pathway
 Ca2+  CaMK activation  interaction between
MEF2 and HDAC   MEF2 transcriptional activities
 Molecular pathways for
skeletal muscle hypertrophy 4
 Calcium-calmodulin protein kinase (CaMK)
pathway
 Ca2+  CaMK activation  interaction between
MEF2 and HDAC   MEF2 transcriptional activities
 Molecular pathways for
skeletal muscle hypertrophy 4
 Calcium-calmodulin protein kinase (CaMK)
pathway
 Ca2+  CaMK activation  interaction between
MEF2 and HDAC   MEF2 transcriptional activities
 Molecular pathways for
skeletal muscle hypertrophy 4
 Calcium-calmodulin protein kinase (CaMK)
pathway
 Ca2+  CaMK activation  interaction between
MEF2 and HDAC   MEF2 transcriptional activities
 Molecular pathways for
skeletal muscle hypertrophy 5
 Insulin-like growth factor (IGF)-1
 IGF-1 with important functions for muscle growth
 IGF-1 overexpression in mice  muscle hypertrophy
 IGF-1  satellite cell activation

 IGF-1 pathways
① PI3K
② Akt
③ mTOR
④ P70
  protein synthesis
 Molecular pathways for
skeletal muscle hypertrophy 5
 Textbooks

Pages 128-139; Chapter 28 Pages 927-943;

 Contents in brief 2
9) General features of connective tissues
10) Connective tissue extracellular matrix
11) Proteoglycans
12) Collagen
13) Elastin and laminin
14) Integrins and fibronectin
Connective tissues, fibres, and ground substances
 General features of connective
tissues
 Connective tissues
 Composed of extracellular matrix (ECM) and cells
 Fill up spaces between cells  bind cells together
 Determine the shape/partitioning of tissues

(Sattar's OC)
 General features of connective
tissues 2
 Extracellular matrix (ECM)
 Protein fibres
 Ground substance

 Connective tissue cells

 Fibroblasts: secret protein fibres and ground substance
 Adipocytes: store fats
 White blood cells (WBCs): many types of WBCs
present in connective tissues

(Sattar's OC)
Connective tissue extracellular
matrix
 Ground substance
 Connective tissue component between cells and
fibres
 Support cells and/or bind cells together
 Store/trap water
 May be fluid, semifluid, gelatinous, or calcified
 Substance exchange medium between blood and
cells
 Major components
 Glycosaminoglycans (carbohydrate part of
proteoglycan)
 Proteoglycans
 Connective tissue extracellular
matrix 2
 Fibres
 Three types of fibres
 Collagen fibres
 Consist of collagen protein
 With great tensile strength
 Present in connective tissues, such as bone,
cartilage, tendons, liagments, etc
 Elastic fibres
 Consist of elastin protein surrounded by
fibrillin glycoprotein
 With high elasticity
 Present in skin, blood vessel walls, lung
tissues, etc
(McGraw-Hill Education)
Collagen fibres

(Sichuan University)
Elastic fibres

(nature.com)
 Connective tissue extracellular
matrix 2
 Fibres
 Three types of fibres
 Reticular fibres
 Consist of collagen protein in fine bundle
coated with glycoprotein
 Provide support and strength
 Present in walls of blood vessels
 Present in network around the cells in tissues,
such as areolar connective tissue, adipose
tissue, etc
 Present in the stroma/supporting framework
of soft organs, such as spleen, lymph nodes,
etc
Connective tissue extracellular
matrix 3

(McGraw-Hill Education)
 Proteoglycans
 Gel forming component: ground substance
 Consist of glycosaminoglycans (GAGs) + a core protein
 GAGs: polysaccharides with disaccharide repeating
units
 One sugar is either N-acetylglucosamine or N-
acetylgalactosamine
 The second sugar is either glucuronic acid or
iduronic acid
 >95% carbohydrates by weight
 Contain negatively charged group  H-bond to trap H2O
molecules
 May form large aggregates by attaching to hyaluronic
acid
 Proteoglycans 2 GAGs
Core protein
Hyaluronic acid
Proteoglycans

(studyblue.com)
 Functions of proteoglycans
 Found in interstitial connective tissues, such as synovial
fluid, bone, cartilage, etc
 Interact with collagen, elastin, laminin, etc
 Negatively charged groups  repel to occupy large
space
 Molecular sieves of substance
transport
 osmotic force to resist pressure
 Permit flexibility, compression,
and re-expansion

(the British Institute of Radiology)

Protein molecules in the connective tissues
 Collagen
 A family of fibrous proteins
 Triple helical structure
 30% of total protein in the body
 Principally synthesized by fibroblasts,
muscle cells, and epithelial cells
 25 collagens identified
 Type I collagen
 Most abundant protein in mammals
 Major components of connective tissue
 Consist of glycine, proline, and hydroxyproline
Elastin and laminins
 Elastin
 Predominant protein in elastic
fibres
 Provide flexibility for functions of
blood vessels, lungs, ligaments,
skin, etc

 Laminins
 Glycoproteins found in basement
membranes
 Cross-shaped heterotrimeric
molecules: -, -, and -chains
 Form mesh-like network
 Integrins and finbronectin

 Integrins
 Bridge internal cytoskeleton of
cells to extracellular proteins,
such as collagen, laminin, etc

 Fibronectin
 Found in ECM
 Link integrins to ECM
components  cell positions in
ECM

(IDM Ltd)
Integrins and finbronectin 2

(IDM Ltd)
 Summary 6

Collagen fibres

Laminin

Cytoskeleton
Elastic fibres

Integrin
Reticular fibres

Fibronetin
Proteoglycans
End