Bone Metabolism/Homeostasis

Question 1

Skeletal muscle cells are mostly packed with?

Answer 1

• Myofibrils
  
  • bulk of cytoplasm is myofibrils ( contractile elements)

Question 2

• Myofibrils in skeletal muscle cells are made of?
• How do these interact to produce contraction?

Answer 2

• Actin and myosin
  
  • Myosin head has ATP binding site and ATPase activity
  • ATP binding and hydrolysis change the conformation of myosin allowing its head to cyclically associate/dissociate from actin
  • resulting in forward sliding actin filament

Question 3

Power physical performance that is short (few seconds), is supported by which energy sources?

Answer 3

• ATP and Creatine phosphate (Phosphocreatine; PCr)
• Immediate energy source

Question 4

Speed/ spurts of activity that last several seconds to a minute use which type of energy source?

Answer 4

• ATP generated from rapid anaerobic/ nonoxidative glycolysis of local muscle gylcogen

Question 5

Endurance activity (>2 minutes) is supported by which energy source?

Answer 5

• ATP from fat oxidation (adipose) and liver glycogen

Question 6

• What is the most abundant and immediate source of ATP in skeletal muscle cells?
• Why are ATP stores so small is muscle?

Answer 6

• Creatine phosphate (have high energy P bonds)
  
  • ATP is low because many reactions are allosterically activated/inhibited by ATP
  • ([] is under very tight control)

Question 7

Reaction from creatine to creatine phosphate is reversible or irreversible?

Answer 7

Reversible (CPK) cells can rapidly recuperate stored energy

Question 8

In power performance, as muscle cells rapidly regenerate ATP from PCr and ADP what builds up?

Answer 8

• AMP accumulates and Myokinase generates ATP from ADP
• Now, AMP accumulates and allosterically activates enzymes (in later steps for energy)

Question 9

In absence of O2 what happens to pyruvate?

Answer 9

• remains in cytosol and is converted to lactate to produce NAD+
  
  • keeps anaerobic glycolysis going

Question 10

In the presence of O2 what happens to pyruvate?

Answer 10

Pyruvate DH links glycolysis to the citric acid cycle

Question 11

Where does anaerobic glycolysis use glucose from to quickly meet the increased energy needs?

Answer 11

local muscle glycogen

Question 12

T/F: anaerobic glycolysis provides rapid but self limited source of ATP

Answer 12

• True
• It has low ATP yield (2 ATP per Glc) and thus muscle rapidly decreases its glycogen stores
  
  • < 2 minutes

Question 13

• How long does it take for the exercise- stimulated increase in blood flow to arrive to muscles?
• What does the blood bring with it?

Answer 13

• Takes >1 min blood flow
• brings:
  
  • O2, glucose and FA
    
    • aerobic glycolysis and oxidative phosphorylation to begin

Question 14

Exercise activates__ and ___ simultaneously

Answer 14

• Glycogenolysis and Glycolysis
  
  • As muscle begins to contract and hydrolyze ATP to ADP, myokinase converts ADP to ATP and AMP accumulates
  • AMP binds and allosterically activates key enzymes of glycogen breakdown (muscle phosphorylase B) and glycolysis (PFK-1 )

Question 15

What two enzymes does increase in AMP activate in glycolysis and glycogenolysis?

Answer 15

• muscle phosphorylase b (glycogen breakdown)
• PFK-1 (glycolysis)

Question 16

What are the two reasons that anaerobic generation of ATP is self limiting?

Answer 16

1. Inefficient:
   
   • anaerobic generation of ATP from muscle glycogen captures only a fraction of energy stored in glucose (2 ATP)
2. Lactate causes acidosis as H+ accumulate

Question 17

• What does the buildup of lactic acid cause during exercise?
• Why?

Answer 17

• muscle cramps
• acidic pH inhibits glycolytic enzymes needed for ATP synthesis and impedes muscle contraction

Question 18

In prolonged exercise, aerobic metabolism is oxidation from non-muscle glucose. What are the three sources of glucose?

Answer 18

1. Liver glycogen
2. Liver gluconeogenesis
3. Lactate
   
   • produced during anaerobic glycolysis is converted back to glucose by Lactate DH and Lactic acid cycle (Cori cycle)

Question 19

What are the two fates of lactate?

Answer 19

1. As blood flow and O2 delivery increases, muscle converts accumulated lactate back to pyruvate via pyruvate DH
   
   • subsequent oxidation by mitochondria (75%)
2. 25% of lactate is released into the bloodstream and enters the liver for Gluconeogenesis

Question 20

Gluconeogenesis is important in exercise lasting?

Answer 20

> 1 hour

liver glycogen stores are depleted

Question 21

What are the substrates for gluconeogenesis?

Answer 21

1. Lactate (Cori cycle):
   
   • Lactate is taken by liver and converted to Glc and returned to muscle
2. Alanine:
   
   • Pyruvate is converted to Ala in muscle which is exported to liver—>
   • converted to pyruvate (which enters gluconeogenesis)—>
   • Glc exported back to muscle for energy

Question 22

• Epinephrine that is released during exercise stimulates which process in the liver?
• Cause an increase in?

Answer 22

• Stimulates glycogenolysis and gluconeogenesis
  
  • by causing cAMP levels to increase

Question 23

Liver glycogen becomes a source of Glc that the muscle oxidizes. This is because exercise increases what two hormones?

Answer 23

1. Glucagon
2. Epinephrine

both hormones stimulate breakdown of liver Glycogen which increases Glc hepatic output

Question 24

How does exercise increase muscle Glc intake?

Answer 24

• Insulin independent process!
• Contraction induces translocation of GLUT 4 transporters from cytosol to plasma membrane

Question 25

Release of Glc in the blood is controlled by?

Answer 25

Insulin and Exercise

Question 26

* Glucagon and epinephrine released during exercise activate which process by which enzyme? * Via which receptors?

Answer 26

* **Activate glycogenolysis** to increase liver glucose output * Bind via G-protein coupled receptors---\> * increase cAMP---\> activate kinases-\> * ***glycogen phosphorylase a*** degrades glycogen to G-1-P

Question 27

* Insulin and exercise increase Glucose transport into skeletal muscle by recruiting what to the plasma membrane? * What specifically happens during exercise?

Answer 27

* **GLUT4** * Muscle contraction increases Ca2+ and AMP * in turn activate AMPK * **activated AMPK** stimulates GLUT4 translocation * increase Glc uptake during exercise

Question 28

Exercise and insulin stimulate different stores of GLUT 4. Thus have additive effects on Glc transport into skeletal muscle. Effects with Diabetes?

Answer 28

* Insulin dependent translocation of GLUT4 is impaired in diabetes * **Exercise- induced activation of GLUT4 remains intact in diabetes** * ( allows glucose to enter muscle cells at normal levels in diabetics) * Why 1/3 treatment is exercise

Question 29

In very prolonged exercise, what does the muscle rely on for ATP?

Answer 29

* **Free FA** (make up to 60%) * Resting skeletal muscle uses free FA as a principle source of fuel at almost any time **except postprandial state,** * free FA are preferred fuel for skeletal muscle

Question 30

Where are sources of FA oxidation during exercise?

Answer 30

* Skeletal muscle (stores a little as triacylglycerol) * Adipocytes

Question 31

Mobilization of lipid from adipocytes is controlled by ___ during prolonged exercise?

Answer 31

* The sympathetic NS (**epinephrine**) and release of **growth hormone** during lasting exercise

Question 32

* Uptake of FA into the mitochondria via CPT-1 is inhibited by?

Answer 32

**Malonyl-CoA**

Question 33

* Malonyl Co-A is produced from? * How does AMP levels affect these?

Answer 33

* **ACC-2:** * **increased AMP inhibits ACC-2**---\> inhibits conversion of acetyl CoA to malonyl CoA--\> * more FA taken into mitochondria * **MCoADC** * **increase AMP activates MCoADC**---\> promotes conversion of Malonyl CoA to acetyl CoA---\> * more FA uptake into mitochondria

Question 34

T/F Muscle cells synthesize fatty acid

Answer 34

* FALSE * Muscle cells don't synthesize FA * ACC-2 which converts acetyl CoA---\> malonyl CoA is only for regulatory purposes

Question 35

Free FA are preferred fuel for skeletal muscle, except during postprandial state. What happens during that time?

Answer 35

* Glucose is converted to pyruvate which is converted to citrate * **excess citrate** leaks out of mitochondria---\> * a**llosteric activation of ACC-2-**--\> increase in malonyl CoA---\> * inhibits entry of FFA into mitochondria

Question 36

Slow twitch muscle fibers (Type 1) * Fatigue: resistant or not? * Color? * Metabolism? * Mitochondria level? * Glycogen levels?

Answer 36

* Resistant to fatigue * Large amount of myoglobin within cytoplasm (red) * facilitates O2 delivery * Mostly oxidative metabolism * because high mitochondrial and oxidative enzyme content * low glycogen and glycolytic enzyme activity ( develop force slowly but maintain contraction longer)

Question 37

* Fast twitch fibers Type IIa are similar to slow twitch fibers with respect to? * Difference?

Answer 37

* _Similar:_ * Mb (red), more mitochondria, reliance on oxidative metabolism and fatigue resistant * _Difference:_ * abundant glycogen ensures adequate energy generation for fast twitching

Question 38

Difference between fast twitch type IIa and type IIb?

Answer 38

IIb is more fatiguable than IIa

Question 39

What muscles do slow twitch fibers predominate?

Answer 39

* Skeletal muscles that don't need to contract rapidly but must be resistant to fatigue and able to maintain tension for long periods of time * **back muscles**

Question 40

Fast twitch fibers are more prevalent in which muscles?

Answer 40

* muscles of the limbs that are responsible for sudden powerful movements

Question 41

McArdle disease is genetic deficiency in?

Answer 41

* **muscle glycogen phosphorylase** * benign since the patient only experience fatigue and muscle cramps during exercise

Question 42

Hers disease is a genetic deficiency in?

Answer 42

* **liver glycogen phosphorylase** * liver glycogen is first reservoir for support of blood glucose * can cause life threatening hypoglycemia during fasting