Biochem revision - Week 8 Integration of Exercise Metabolism

Question 1

In a carbohydrate shortage in the liver (lack of oxaloacetate), what pathway will be utilized during exercise?

Answer 1

In a carbohydrate shortage in the liver cells, ketogenesis will occur due to the lack of oxaloacetate (oxaloacetate joins with acetyl coA to start the TCA cycle) because it is being used for gluconeogenesis by the liver.

Ketone bodies formed in the liver via ketogenesis will be transported through the blood to working muscle where it will form acetyl coA through ketolysis and be used in the TCA cycle to produce ATP

Question 2

What are the four main metabolic pathways that pyruvate can enter?

Answer 2

Pyruvate can:

1. Convert to oxaloacetate originally from lactate or pyruvate, to undergo gluconeogenesis or into the TCA cycle when there is an abundant amount of acetyl coA
2. Convert to acetyl coA to then react w/ oxaloacetate to enter the TCA cycle
3. Be converted to alanine via transamination of proteins in order to be used for gluconeogenesis in the liver and then be shuttled back to working muscle (Glucose-Alanine Cycle)
4. Be converted to lactate via pyruvate dehydrogenase

Question 3

What pathways do the products of TAG breakdown/lipolysis follow?

Answer 3

Glycerol -

Glycerol can be connected to glycolysis and thus gluconeogenesis in the liver

Fatty acids -

Fatty acids can be degraded into acetyl coA through B-oxidation

*Both compounds can also be channeled back into triacylglycerol synthesis

Question 4

What metabolic pathways can acetyl coA follow?

Answer 4

Acetyl coA can enter the TCA cycle to produce ATP, or
if there is limited oxaloacetate, it can undergo ketogenesis
or it can converted back into acyl coA to reform fatty acids

Question 5

What metabolic routes can proteins follow?

Answer 5

Various routes to the TCA cycle including ketolysis or a-ketoglutarate, as well as what is remaining of the amino acids (carbon skeletons) following these rctns to enter the TCA cycle as other compounds such as pyruvate, acetyl coA etc.

Proteins can degrade into amino acids then into protein synthesis of creatine for the PCr cycle

*Proteins also form ammonium during deamination that is converted to urea (neutralized)

Question 6

What are the 3 categories of energy systems? Briefly describe them.

Answer 6

1. Aerobic system - oxidative phosphorylation occurs simultaneously with glycogenolysis in muscle and liver Time = >60s
2. Anaerobic system - anerobic glycolysis; lactate dehydrogenase converts pyruvate and NADH to lactate and NAD+ to recycle into glycolysis Time = 7-60s
3. ATP/PCr system - Creatine Kinase can rapidly reform ATP by transferring it’s phosphoryl group to ADP
   Myokinase can also reform ATP by adding molecules of ADP together to form ATP and AMP Time = <7s

Question 7

How much time do each of the E systems provide fuel for? What is the fuel for each system and it’s biproducts?

Answer 7

Aerobic
Time = >60s
Fuel = Carbs, lipids, proteins
Biproducts: CO2, H2O

Anaerobic
Time = 7-60s
Fuel = Carbs (glucose)
Byproducts: Lactic acid

ATP/PCr (remember including myokinase)
Time = <7s
Fuel = ATP/ADP/PCr
Byproducts: AMP, Pi

Question 8

What kind of exercise is aerobic lipolysis best suited for? Until what intensity?

Answer 8

Low intensity exercise. Until about 55% VO2 max

Question 9

At moderate exercise intensities, how are the different E systems being utilized?

Answer 9

Aerobic carbohydrate and lipid breakdown occur.

As exercise continues @ same intensity, proportion involvement of lipid catabolism is favored.

Question 10

What are the sources of E metabolism during maximal exercise?

Answer 10

Limited/smaller E depots are depleted in the first 7s for PCr, and the first 7-60s for anaerobic metabolism. Larger E availability from oxidative phosphorylation is then the sole source of E until resources are gone

Question 11

What molecule does gluconeogenesis use in order to form glyceraldehyde-3-phosphate? (Which is then isomerized and dephosphorylated into glucose-6-phosphate)

Answer 11

NADH

*When Lactate is used for gluconeogenesis, the NADH is provided upon its conversion to pyruvate, thus it is a shortcut to regular gluconeogenesis for pyruvate

Question 12

What is carb loading?

Answer 12

When someone decreases their carb intake 7-8 prior to an event, then ingests excess 2-3 days before to increase glycogen stores to above baseline

Question 13

What are the use of medium-chain triacylglycerols (MCTs)?

Answer 13

MCTs are short acyl chains that contain 8-12 carbons.

They have no need for carnitine transport into the mitochondria like Long-Chain TAGs do, thus they may provide fast additional E if ingested during long aerobic exercise

Question 14

Can muscle fiber types be ‘trained’?

Answer 14

Yes. Under the correct conditions, some fibers can transition from glycolytic, to decreased neuromuscular activity and vice versa.

Question 15

How are someone’s muscle fiber types determined?

Answer 15

Muscle contains a mixture of all 3 fiber types but proportions are largely genetically determined

Question 16

What type of muscle fiber is highly glycolytic, with low resistance to fatigue?

Answer 16

IIX fibers

Question 17

What type of muscle fiber has intermediate myosin ATPase activity, resistance to fatigue, economy (volume of O2 required) and maximal shortening v?

Answer 17

IIA fibers

Question 18

What is the Respiratory Exchange Ratio?

Answer 18

The RER is the volume of expired CO2 compared to O2 consumed.

*This number ranges from 0.7 -1.0, 0.7 meaning more lipids are oxidized than CHO and 1.0 meaning that more carbs are being oxidized than lipids

Question 19

What does a Respiratory Exchange Ratio above 1 mean?

Answer 19

A RER above 1 means that the exercise is anaerobic because more CO2 is being expelled than O2 inhaled

Question 20

What does it mean to have a high metabolic flexibility capacity?

Answer 20

Having a higher metabolic flexibility means that someone will be more efficient at switching substrates - or adapting - based on the exercise demand.

Ex. During an overnight fast, someone with greater metabolic flexibility will be able to switch to fat oxidation faster than someone else, and will therefore also have a lower RER overnight

Ex. Someone who begins on a high fat diet will be able to lower their RER faster than someone else

Question 21

What is the effect of endurance training on the contribution of E stores?

Answer 21

Carb stores will be used less/at a slower rate, and lipid metabolism contribution increases

The benefit is ‘sparing’ the carbohydrates, which allows the athlete to exercise at a higher intensity while spending the same amount of carbs

Question 22

What are four ways that training effects the proportion of E sources used during exercise?

Answer 22

1. Muscle mitochondria content increases
2. Glucose uptake decreases for a given intensity of exercise (lower translocation to plasma membrane of muscles at given intensity, although the total [GLUT4] increases)
3. The rate of glycogenolysis decreases
4. Fatty acid uptake increases

Question 23

What E system is fatigue caused by ‘decreased muscle excitation’?

Answer 23

Muscle fatigue in the lactate system and oxygen system is associated with decreased muscle excitation

Question 24

Which E system is fatigue caused by RONS (Reactive Nitrogen Species) associated with?

Answer 24

The aerobic energy system can be fatigued by RONS accumulation

Question 25

What are the stages of RONS accumulation?

Answer 25

1. Initiation

• The first molecule is produced (ex. superoxide anion)

2. Propagation

• A cascade of e- in redox rctns occur producing damaging oxides for example

3. Termination

• An enzyme eventually catalyzes a rctn that ‘neutralizes’ the ions into H2O and O2 for example

Question 26

How/when are RONS produced?
What are the consequences?

Answer 26

e- can leak from the ETC, furthering reducing other molecules

This can increase when working muscle increases the demand for ATP

If antioxidant species are outweighed, oxidative damage can occur, ultimately resulting in reduced/loss of function in muscle contractile force

Question 27

How is muscle ATP replenished? How is muscle PCr replenished?

Answer 27

Oxidative phosphorylation replenishes muscle ATP

ATP and Creatine intake replenishes muscle