Module 2: Non oxidative and oxidative metabolism during exercise

Question 1

Explain the rate vs duration tradeoff with regards to ATP supply:

Answer 1

PCr: provides ATP rapidly for a short duration of time
Glycolytic: provides ATP at a reasonable rate for a moderate duration of time
Oxidative: provides ATP slowly for a longer duration of time

Common pattern: the longer the duration, the greater the decrease in the rate of ATP production

Question 2

What role does phosphocreatine play in ATP production?

Answer 2

PCr buffers decrease in ATP - when levels of ATP start to drop, PCr steps in and prevents rapid decline. Process is instantaneous but the substrate is quickly depleted. One unit of ATP is generated per unit of substrate.

Chemical reaction: PCr + ADP + Creatine kinase -> ATP + Cr
^ enzyme that facilitates reaction

Question 3

When do we heavily rely on PCr stores?

Answer 3

1. Working at a high intensity - 100m sprints
2. Rest to work transitions - getting up out of your chair and starting to walk
3. Workload transition - biking up a flat surface to a hill

Question 4

How does one increase his/her PCr regeneration speed?

Answer 4

With endurance training or the supplementation of creatine

Question 5

What is the basic theory with regards to creatine supplementation? For what situations does it work, are there any issues associated with it?

Answer 5

If you supplement creatine at rest when you already have ATP available, the following chemical reaction will occur.

ATP + Cr -> ADP + PCr

ADP and PCr are the substrates needed to produce ATP. If we have more of them, we will be able to generate more energy.

Works for brief, intense, and repeated bouts of exercise. Potential issues are one may experience weight gain (water).

Question 6

What is non oxidative glycolysis?

Answer 6

Partial breakdown of glucose/glycogen without the presence of oxygen. It is usually engaged in the onset of exercise or rest to work transitions (15s - 2 min) as oxygen is not able to get to the muscle quick enough. It is a rapid process but is limited by metabolic byproducts. Produces 2-3 ATP per unit of substrate.

Question 7

Where is the majority of glycogen stored within the muscle?

Answer 7

Intermyofibrillar layer, ~75% of it is stored here

Question 8

Define glycolysis:

Answer 8

The breakdown of one glucose molecule to form 2 pyruvate molecules

Question 9

Define glycogenolysis:

Answer 9

The breakdown of one “glucose unit” from glycogen to form G1P

Question 10

Provide a brief overview of the glycolytic system:

Answer 10

Glucose from the bloodstream is transported into SKM by GLUT-4 transporters.

With glucose: 1 glucose molecule (6 carbon), with 1 ATP and the enzyme hexokinase (takes the phosphate group from ATP and attaches it to the 6th carbon of glucose trapping into SKM) is converted to G6P

With glycogen: 1 glycogen molecule is converted to G1P via the enzyme glycogen phosphorylase, which is converted to G6P

G6P is converted to 2 molecules of pyruvate (3 carbon) with 1 ATP and the rate limiting enzyme phosphofructokinase (PFK), producing 4 ATP in the process (known as substrate level phosphorylation - forming ATP without oxygen) and 2 NAD+ which is reduced to 2NADH + H+

Question 11

What is the net ATP gain from glucose and glycogen in the glycolytic system?

Answer 11

Glucose: 2
Glycogen: 3

Question 12

What regulates the rate limiting enzyme phosphofructokinase (PFK)?

Answer 12

ADP and ATP concentrations:

+ADP = +PFK = +glycolysis
+ATP = -PFK = -glycolysis

Question 13

What are the two potential fates of pyruvate?

Answer 13

1. If oxygen is available, it can be converted to acetyl CoA via the enzyme pyruvate dehydrogenase (PDH) in the mitochondria. NADH + H+ which was reduced prior enters the mitochondria where it reforms back to NAD+.
2. If oxygen is not available, converted to lactate via the enzyme lactate dehydrogenase (LDH) in the cytosol. NADH + H+ is oxidized to form NAD+

NAD+ is needed in order for the process of glycolysis to occur - prevents the accumulation of H+ ions which make the muscle more acidic, causing metabolic inhibition (decreased enzyme activity) and contractile inhibition (decreased cross bridge cycling)

Question 14

When do we rely heavily on non oxidative glycolysis?

Answer 14

1. Intense exercise
2. Rest to work transitions
3. Workload transitions to exercise

Question 15

What are three potential functions of lactate?

Answer 15

1. mitochondrial respiration
2. gluconeogenic precursor
3. Signaling molecule

Question 16

What is oxidative metabolism?

Answer 16

Complete breakdown of CHO, fats, and AA’s to the products of CO2 and O2. It is a process that requires oxygen but can provide sustained energy. Occurs within the mitochondrion of a muscle cell. Produces over 30 units of ATP per substrate.

Question 17

With regards to the mitochondria, what is the path in which H+ ions are pumped?

Answer 17

Matrix (space inside of the inner membrane) to the intermembrane space

Question 18

Where does the ETC occur within the mitochondria? Describe what takes place within this process (chemiosmotic theory)

Answer 18

Inner membrane.

There are a series of complexes. At complex 1, NADH is oxidized to NAD+ with a simultaneous reduction of the complex. 2 H+ ions are pumped from the matrix through to the intermembrane space. NADH is oxidized before FADH2 which an integral reason to why it produces more ATP.

At complex 2, FADH2 is oxidized to FAD+ with a simultaneous reduction of the complex.

At complex 3, 2 H+ ions are pumped from the matrix through to the intermembrane space

At complex 4, O2 is reduced and becomes H2O (one way reaction) via the enzyme cytochrome oxidase. 2 H+ ions are pumped from the matrix through to the intermembrane space

At complex 5, the 6 H+ ions get pumped from the acidic intermembrane space (more positive) back to the matrix to produce energy. Allows ATP synthase to form ATP via the reaction ADP + Pi -> ATP.

Every 2 H+ pumped back into the matrix = 1 ATP, 3 ATP GENERATED

Question 19

What are the three essential steps in oxidative metabolism?

Answer 19

1. Formation of Acetyl CoA (CHO, fats, AA’s)
2. Oxidation of Acetyl CoA (Krebs cycle), simultaneous reduction of coenzymes (NAD+ to NADH + H+, FAD+ TO FADH2
3. Formation of ATP (ETC), simultaneous oxidation of coenzymes (NADH + H+ TO NAD+, FADH2 TO FAD+), reduction of oxygen to produce H2O

Question 20

With regards to the first essential step in oxidative metabolism, provide the detailed chemical reaction that occurs from a carbohydrate: Where is PDH found in terms of the mitochondria?

Answer 20

Formation of Acetyl CoA

Pyruvate + NAD + pyruvate dehydrogenase -> Acetyl CoA + CO2 + NADH

Pyruvate = 3 carbon molecule
Acetyl CoA = 2 carbon molecule
1 carbon is lost via CO2
PDH is found in the inner mitochondrial membrane

Question 21

Provide a brief overview of the Krebs’s (TCA) cycle:

Answer 21

A 4 carbon molecule oxaloacetate and a 2 carbon molecule Acetyl CoA form a 6 carbon molecule citrate with the enzyme citrate synthase (important marker of how much mitochondria an individual has within their muscles)

2 carbon molecules are lost via CO2

The production of 3 NADH, 1 FADH2, 1 ATP per cycle (multiply by 2 for 2 Acetyl CoA’s)

Question 22

How much ATP is generated from one molecule of NADH and FADH2 in the ETC?

Answer 22

2.5 per NADH and 1.5 per FADH2, less than 3 and 2 because of ATP transport

Question 23

With regards to oxidation-reduction reactions, where are electrons carried?

Answer 23

Carried on the H+ molecules

I.e., 2 H+ (2H+ + 2e-)

Question 24

How much ATP is produced from carbohydrates (glucose and glycogen) anaerobically?

Answer 24

2 from glucose and 3 from glycogen

Question 25

How much ATP is produced from carbohydrates (glucose and glycogen) aerobically?

Answer 25

32 from glucose and 33 from glycogen

glucose:
glycolysis: 4 ATP produced - 2 which are used, 2 NADH = 7 ATP
PDH rxn: 2 NADH = 5 ATP
TCA/ETC: 6 NADH, 2 FADH2, 2 ATP = 20 ATP
net = 32 ATP

glycogen:
glycolysis: 4 ATP produced - 1 used, 2 NADH = 8 ATP
PDH rxn: 2 NADH = 5 ATP
TCA/ETC: 6 NADH, 2 FADH2, 2 ATP = 20 ATP
net = 33 ATP

Question 26

What is a triglyceride composed of?

Answer 26

A glycerol + 3 FA’s

Question 27

Where are the two main locations triglycerides are stored within the body?

Answer 27

Adipose tissue (largest store), skeletal muscle

Question 28

What type of fats do humans usually rely on for metabolism? Provide an example:

Answer 28

Saturated fatty acids. Palmitate which is a 16 carbon FA.

Question 29

What are the seven stages of lipid catabolism? Describe what happens within each stage:

Answer 29

1. Mobilization - Lipolysis of TG, broken down into one glycerol which is sent to the liver to be repurposed into glucose, 3 FA’s which can be sent to muscle to be catabolized for energy. Hormone sensitive Lipase (HSL) is the enzyme which facilitates this reaction and it can be signaled by the catecholamines which are activated during exercise (NE AND E)
2. Transport - FA circulates in blood via the protein albumin
3. Uptake - FA enters muscle cytosol
4. Activation - FA is combined with a CoA to produce fatty acyl-CoA, process expends 2 ATP but allows the FA to be recognized by the mitochondria
5. Uptake - fatty acyl-CoA enters the mitochondria via the enzyme carnitine palmitoyl transferase (CPT)
6. Beta oxidation - FA is broken down in mitochondria via the enzyme beta HAD
   Per cycle of beta oxidation using a fatty acyl CoA, 1 NADH & 1 FADH2 are produced, and 1 Acetyl CoA is generated
   #of cycles: total # of carbons divided by 2, minus 1 (when two carbon are left, Acetyl CoA is generated automatically and beta oxidation does not occur)
   To calculate ATP yield: 14 ATP x # of turns + 8 = total yield
7. Mito oxidation - TCA cycle / ETC activity

Question 30

What is a popular claim with regards to carnitine as a weight loss supplement?

Answer 30

Great for weight loss and will help optimize fat conversion to energy during exercise. In reality, it is not very effective

Question 31

With regards to CHO and fat, which fuel source is more O2 efficient?

Answer 31

CHO is ~10% more O2 efficient (5.3 ATP per O2 compared to 4.6 ATP per O2), and permits exercise at a higher pace

Fat is preferred at rest because we an unlimited capacity
CHO during exercise

Question 32

When do we rely heavily on oxidative metabolism?

Answer 32

1. Rest
2. Steady state exercise
3. Exercise lasting longer than 2 minutes

Question 33

What is an amino acid composed of?

Answer 33

Amino group (nitrogen), R group (the part which differentiates each AA), carboxyl group

Question 34

How do AA’s generally get catabolized?

Answer 34

1. Removal of the amino group - major site where this occurs is the liver, minor site where it occurs is SKM (BCAA’S). In SKM, glutamine and alanine carry the nitrogen out to the bloodstream and to the liver where it is converted to urea and is excreted by the kidneys.
2. Oxidation of remaining carbon skeleton (oxo acid) - form pyruvate or Acetyl CoA.

Question 35

What are some major AA’s in exercise metabolism?

Answer 35

BCAA’S (leucine, isoleucine, valine)

Question 36

What is gluconeogenesis?

Answer 36

the formation of glucose from metabolic intermediates. From SKM - lactate and alanine, adipose tissue - glycerol, go to the liver where glucose is reformed and exits back to SKM.