Module 6 - Cell Signalling and Molecular Regulation of Exercise Metabolism

Question 1

Almost all of the information to make proteins within the body, including those for structure (such as actin, troponin) and function (enzymes like glycogen phosphorylase) are coded by…

Answer 1

A sequence of nucleotides that make up DNA code with the cell’s nucleus.

Question 2

Skeletal muscle cells are quite specialised, as unlike most other cells in the body they are…

Answer 2

multi-nucleated

= each muscle cell (i.e. fiber) contains many nuclei

Question 3

The human genome contains 3164.7 million chemical nucleotide bases

A, C, G and T

Answer 3

A = Adenine

C = Cytosine

G = Guanine

T = Thymine

Question 4

Nucleotide bases are arranged into triplets called…

Answer 4

Codons

e.g. = ACG, AAA or TAG

Question 5

Each codon specifies the identity of either…

Answer 5

1. single amino acid; or
2. stop signal

Question 6

The codon CAG represents

Answer 6

The amino acid glutamine

Question 7

The codon TAA represents

Answer 7

A stop codon

Question 8

The average gene consists of…

Answer 8

3000 bases, but sizes vary

largest known gene is dystrophin with 2.4 million bases.

Question 9

The total number of genes is estimated at…

Answer 9

20,000 to 25,000 and this is much lower than previous estimates of 80,000 to 140,000.

Allows for synthesis of 100,000 to 200,000 different proteins.

Question 10

Almost all (___%) nucleotide bases are exactly the same in all people and the functions are unknown for over ___% of discovered genes.

Answer 10

99.9% ; 50%

Question 11

In addition to the ~25,000 genes that are contained within the DNA of the nucleus, the mitochondria also contain their own DNA (called ____), which consists of just __ genes that encode just __ proteins located in the __________________________________________

Answer 11

mtDNA

37

13

electron transport chain of the mitochondria

Question 12

You get a copy of _____ ____ from each of your parents. However, you inherit your ____________ ___ (_____) exclusively from your mother

Answer 12

nuclear DNA

mitochondrial DNA (mtDNA)

Question 13

Polymorphism (i.e many forms)

Answer 13

describes the ways in which gene sequences might differ between people.

One obvious example is how males and females differ due to genes on X and Y chromosomes.

Question 14

Single Nucleotide Polymorphism

Answer 14

a difference in variation of 1 nucleotide for the same gene encoded between people, or within 1 person between paired chromosomes.

Question 15

Perhaps the best known example of a SNP and how it relates to athletic traits and performance is the _______ _ (_____) ____________

Answer 15

actinin 3 (ACTN3) polymorphism

Question 16

Actinin

Answer 16

key structural protein found at Z line

anchors actin filaments in muscle

Question 17

It was discovered back in 1999 that ~__% of the population are deficient in ‐_______‐ protein due to a ___ on the _____ gene.

Answer 17

18

α‐actinin‐3

SNP

ACTN3

Question 18

The codon for the amino acid “arginine” is

Answer 18

CGA

Question 19

Whereas, TGA is

Answer 19

a stop codon

a SNP whereby the nucleotide Cytosine, is replaced by Thymine in this particular codon will stop the ACTN3 gene from being expressed and translated into actinin 3 protein

Question 20

Myostatin

Answer 20

• naturally occurring protein secreted by the body to inhibit muscle growth by inhibiting the protein synthesis pathway.
• acts as a natural brake to prevent excessive protein synthesis.
• myostatin gene is normally expressed in skeletal muscle.

Question 21

However, there are reports of rare, but naturally occurring mutations in the myostatin gene that prevent the translation of _________ ____ into _________ _______.

Answer 21

myostatin mRNA

myostatin protein.

Question 22

Image: case study of a baby who…

• Reported to be healthy, but unusually strong and muscular.
• Cross-sectional area of his quadriceps was double that of an unaffected child.

Reasons?

Answer 22

• Double mutation in myostatin gene
• Produced no myostatin protein
• 3 generations of his family were reported to be unusually strong and his mother was a former professional athlete.

Question 23

We now know that one of the key ways in which tissues (i.e. skeletal muscle) adapt following training is that each bout of exercise is a stimulus to increase _____________ __ _____ that are relevant to the ________ ________.

Answer 23

transcription of genes

training response.

Question 24

exercise physiologists measured the mRNA levels (a measure of transcription) of an important protein involved the synthesis of mitochondria (called PGC-1α)

They took muscle biopsies at rest (Pre) and then immediately after (0’) and then 2, 6 and 24 hrs after a single bout of endurance exercise.

What this data shows is that the gene expression of PGC-1α is ___________ ___________ for several hours following exercise and it then _______ __ _____ ______ by 24 hours post exercise.

Following the increase in ____ __________ (measured by mRNA levels) there will likely be an increase in ___________ of this protein.

Answer 24

transiently upregulated

returns to basal levels

gene expression

translation.

Question 25

Skeletal muscle has a remarkable capacity to not only adapt to __________ ________ by increasing ______ ___________ and strength but also to __________ ____ ______.

Answer 25

resistance training

muscle hypertrophy

regenerate from injury

Question 26

As mentioned earlier, skeletal muscle fibers are ______________, containing hundreds of nuclei located just _____ ___ ____ ________ (__________).

Answer 26

multinucleated

under the cell membrane (sarcolemma)

Question 27

Having lots of nuclei per cell results in an enhanced capacity for gene expression and is one of the ways in which skeletal muscle can…

Answer 27

regenerate from injury or adapt so profoundly to exercise compared to other tissues.

Question 28

In a single healthy muscle fiber…

under normal resting conditions muscle fibers aren’t _____.

what are they?

Answer 28

dormant

Rather, there are pulses of transcription occurring at different regions across the muscle fiber, likely undergoing “housekeeping” roles of maintaining the normal function of the cell.

Question 29

Skeletal muscle also has _________ _____ to aid regeneration and hypertrophy

Answer 29

satellite cells

Question 30

Satellite cells

Answer 30

adult stem cells and play an important role in muscle regeneration and hypertrophy.

Question 31

transcription factors are ________ that control the rate of _____________ of genetic information from ___ to ____. They do this by binding to a specific DNA sequence.

Answer 31

proteins

transcription

DNA

mRNA

Question 32

In the case of satellite cells, there are various transcription factors that are ____________ _________ to control important steps during satellite cell muscle regeneration.

We won’t be going into all of these in detail, but three key ones are highlighted in the blue boxes in the figure below (Myf5, MyoD and Myogenin).

Answer 32

sequentially activated

Question 33

Their expression (of Myf5, MyoD and Myogenin) is increased during…

Answer 33

key phases of satellite cell muscle regeneration.

Question 34

Without an increase in these transcription factors (Myf5, MyoD and Myogenin)

Answer 34

satellite cell muscle regeneration is impaired.

Question 35

Note that they are primarily involved in regulating certain stages of the pathway – for example, MyoD plays a key role in…

Answer 35

driving satellite cell proliferation.

Question 36

When exercise physiologists took muscle biopsies, several hours following two bouts of resistance exercise.

MyoD and Myogenin increase post exercise and return back to baseline eventually.

However, note that MyoD _____ and then ________ much earlier, whereas Myogenin _____ much later post exercise.

Answer 36

peaks

declines

peaks

Question 37

When exercise physiologists took muscle biopsies, several hours following two bouts of resistance exercise.

This is consistent with the earlier role of MyoD in satellite cell _____________ and the latter role of Myogenin in satellite cell _______________.

Answer 37

proliferation

differentiation

Question 38

Calcium has many regulatory roles in skeletal muscle.

We learnt how calcium plays a role in the activity of enzymes such as glycogen phoshorylase and pyruvate dehydrogenase to upregulate glycogen breakdown and pyruvate oxidation.

Calcium also has other regulatory roles in the cell and one of these is the…

Answer 38

expression of muscle fiber type.

Question 39

Free calcium levels are different in type I versus type II fibers:

Free calcium level is two-fold higher at rest in type __ (~100 nM) than type __.

Answer 39

I = slow twitch

II = fast twitch

Question 40

However, a characteristic of slow-twitch fibers is that their tonic motor nerve activity at 10–15 Hz results in a sustained elevation of __________ [____] within a concentration range between 100 and 300 nM that can be maintained for _______ _____.

Answer 40

intracellular [Ca2+]

several hours.

Question 41

In contrast, in fast myofibers the resting intracellular [Ca2+] is maintained at levels of only __ nM but phasic motor nerve activity results in ____ ____ _______ (~1000 nM) calcium transients (I.e for shorter duration)

Answer 41

50

very high amplitude

Question 42

Therefore, the intracellular [Ca2+] is ____ _________ in the slow twitch and fast twitch muscle fibers

Answer 42

very different

Question 43

In slow twitch, intracellular [Ca2+] is often sustained at ~___ nM for several hours, whereas in fast twitch muscle there are numerous but ____ ____ intercellular [Ca2+] transients (that can reach 1000 nM).

Answer 43

200

very high

Question 44

Muscle inactivity induces changes to muscle fiber type:

Question 45

As mentioned above, the small but sustained increases in intracellular [Ca2+] are required to drive slow twitch muscle fibre __________. When this doesn’t occur, skeletal muscle typically reverts to the _______, which is expression of fast twitch muscle fibers. A good example of this is the chronic activity seen following nerve ablation (i.e surgical removal of nerves)

Answer 45

expression

default

Question 46

Figure: Muscle biopsies were taken from normal human vastus lateralis muscle (A,B) and vastus lateralis from a paraplegic individual, approx. one year after spinal cord injury (C,D).

In normal healthy muscle

Answer 46

Mix of fast and slow twitch muscle fibers

Question 47

Figure: Muscle biopsies were taken from normal human vastus lateralis muscle (A,B) and vastus lateralis from a paraplegic individual, approx. one year after spinal cord injury (C,D).

In muscle from a person who is paralysed

Answer 47

Complete absence of slow twitch fibers

all muscle fibers are fast twitch

all muscle fibers are much smaller

Question 48

Skeletal muscle has a remarkable ability to adapt to endurance training and produce a high rate of ___ for a __________ period.

Answer 48

ATP

prolonged

Question 49

Adaptations required to increase endurance performance

Answer 49

1. Increase in blood supply to skeletal muscle via an increase in capillary density (angiogenesis)
2. Enhanced ability to transport glucose into the muscle (i.e. increased GLUT4 protein)

Question 50

However, one of the key adaptations required to enhance the capacity of skeletal muscle to generate ATP is by increasing ___________ ______ which enhances the cells capacity to oxidise _____________ and ____.

Answer 50

mitochondrial content

carbohydrates and fats

Question 51

The synthesis of mitochondria (mitochondrial __________) requires an increase in the __________ of mitochondrial genes.

Answer 51

biogenesis

expression