Regulation of fuel use

Question 1

The balance between carbohydrate (CHO) and lipid oxidation during exercise is dependent on a number of factors:

Answer 1

• Nutritional status / diet- can alter the balance e.g. by glycogen loading/ depletion
• Exercise intensity (e.g. above or below LT) once intensity reaches 75% fat reliance declines and energy stores become reliant on blood glucose
• Exercise duration- fatty acid oxidation increases with duration
• Continuous vs intermittent exercise- intermittent exercise can be maintained longer and uses more fatty acids than continuous exercise at the same intensity
• State of training

Question 2

What can the balance between carbohydrate (CHO) and lipid oxidation during exercise be influenced by?

Answer 2

Circulating catecholamines and other hormones

Pharmacological interventions

Question 3

What id arterial FFA conc reflective of?

Answer 3

The arterial FFA concentration reflects a balance between FFA appearance (from adipose tissue) and FFA disappearance (uptake by active muscle)

Question 4

What is used to determine FFA oxidation?

Answer 4

RER

Question 5

What is the energy yield from 16-carbon palmitic acid?

Answer 5

106

Question 6

What is the overall reaction of 16-carbon palmitic acid?

Answer 6

C16H32O2 + 23 O2 + 106 ADP + 106 Pi

–> 16 CO2 + 106 ATP + 122 H2O

Question 7

how much do glycogen and glucose contribute to total energy at the onset of exercise? and after 4 hours?

Answer 7

-60%
-40%
(fatty acid oxidation increases)

Question 8

What happens to RER over 4 hours of constant exercise?

Answer 8

It falls

Question 9

How is carbohydrate oxidation measured?

Answer 9

Repeated muscle biopsy for glycogen content can provide an estimate of CHO oxidation rate during exercise

Question 10

What happens to muscle glycogen after sustained heavy intensity exercise?

Answer 10

Decreases exponentially until around 0

Question 11

What is supercompensation?

Answer 11

After fully depleting glycogen stores we build them up to greater than they were before

Question 12

What was the classical view of nutritional interventions?

Answer 12

Those on a high CHO diet had larger stores and therefore could exercise for longer as there is a linear relationship between the amount of glycogen stored and the exercise capacity

Question 13

What is the effect of altering lipid intake in the days prior to exercise?

Answer 13

Altering lipid intake in the days prior to exercise, has less influence on substrate selection
However, raising plasma FFA may increase muscle fat storage (IMTG), and may influence lipid and CHO oxidation rates during exercise

Question 14

What determines the rate of CHO and FFA oxidation during exercise?

Answer 14

Theories include:

Glucose-fatty acid cycle mediated control of phosphfructokinase activity via [citrate]

Phosphate-mediated regulation of glycogen phosphorylse activity

Redox potential ([NADH]/[NAD+]) mediated control of pyruvate dehyrogenase activity

[malonyl-CoA] mediated regulation of carnitine acyltransferase 1 activity

Carnitine availability for mitochondrial fatty acyl CoA transport

Question 15

What does the glucose-fatty acid cycle

do?

Answer 15

Increasing muscle FFA availability reduces CHO oxidation in cardiac muscle

It also increases acetyl-CoA, citrate, and glucose-6-phosphate (G-6-P)

Question 16

Why does the glucose-fatty acid cycle do what is does?

Answer 16

High [acetyl-CoA] is inhibitory for pyruate dehydrogenase (PDH) by activating PDH kinase. Therefore increasing acetyl CoA it limits PDH activity which limits conversion of pyruvate to acetyl CoA.

High [citrate] (once in the cytosol) is inhibitory for phosphofructokinase (PFK). This may reduce the rate of glycolysis and with a reduced rate of glycolysis G-6-P accumulates

High [G-6-P] inhibits hexokinase (HK) which causes a reduction in the rate of glucose utilization and so reduces glucose uptake into the muscle.

Thus, high FFA availability has been suggested to promote b-oxidation and inhibit CHO oxidation

Question 17

What happens following Triacylglycerol infusion?

Answer 17

Triacylglycerol infusion coupled with heparin (to stimulate lipoprotein lipase activity) during exercise in humans.

Increase in plasma FFA concentration without a major effect on blood [glucose]

This increase in FFA availability decreased glycogen utilisation by 50% during exercise at 80% VO2max, but had no effect on citrate, G-6-P or activity of PDH

Instead, ADP and AMP were lower during the 30 minutes of heavy or very-heavy exercise, which lessens the activation of glycogen phosphorylase (GP) and slows glycolysis

Question 18

What is a role for the mitochondrial redox potential?

Answer 18

Lower cytosolic concentrations of ADP, AMP, and inorganic phosphate (Pi) are seen with high fat provision

Reduced phosphate feedback to the mitochondrion during exercise implicates a greater NADH-delivery to maintain the same flux for oxidative phosphorylation when the VO2 was the same in both conditions

Increased matrix [NADH] inhibits PDH activation suggests glycolysis was reduced

However the experimental support for this theory is weak

Question 19

What happens to RER with increased intensity?

Answer 19

During exercise RER increases proportionally to the relative increase in work rate. As work rate increases, CHO oxidation increases and FFA oxidative decreases:
-The release of FFA into the blood rises in approximate proportion to power output up to LT (~50% VO2max)

• The release of glucose into the blood from the liver increases with power output
• Muscle glycogen use increases exponentially with power output such that below LT the proportion of fatty acids and carbs increase with exercise intensity. BUt above lactate threshold FFA oxidation is reduced and glucose and glycogen metabolism is increased

Question 20

What is the crossover concept?

Answer 20

The crossover point is the relative work rate at which ATP production from CHO exceeds that of lipids. Exercise at power outputs beyond this point will rely more on carbs and less on fats

-As soon as exercise starts, even though the absolute b-oxidation rate increases, the relative proportion (compared to CHO) decreases

Question 21

What happens at exercise onset?

Answer 21

Glucose transporters (GLUT-4) are translocated t o the surface membrane

Cytosolic [Ca2+] and [Pi] are increased by breakdown of ATP and phosphocreatine buffering. Ca release is stimulated by nerves and active muscle

Glycogen phosphorylase is activated

Cytosolic pyruvate and lactate accumulate

Question 22

How is the crossover point displaced after endurance training?

Answer 22

Endurance exercise training to increase VO2max displaces the crossover point to the right

Question 23

How does the ‘crossover concept’ work at high intensity exercise?

Answer 23

1. Acidosis inhibits lipoprotein lipase which is caused by the high rate of glycolytic flux –> fatty acid transport into the cytosol is reduced
2. Because of high rates of glycolysis at the onset of exercise stimulated by ADP, Pi and Ca Pyruvate accumulates which activates pyruvate dehydrogenase and acetyl CoA production in the matrix of the mitochondria.
3. The TCA cycle is activated and citrate accumulates and is transported out of the mitochondria
4. Citrate is a positive allosteric effector of acetyl CoA carboxylase b (ACCb) that, together with malonyl CoA decarboxyase (MDC), regulates [malonyl-CoA] in the cytosol.
5. When flux through glycolysis is high [malonyl-CoA] accumulates and inhibits carnitine palmitoyl transferase 1 (CPT1), which is required for FFA entry into the mitochondrion

Question 24

What is Carnitine acyltransferase 1?

Answer 24

As Fatty acyl-CoA molecules cannot diffuse into the mitochondrion

Fatty acyl-CoA transport occurs via formation of a fatty acid ester with carnitine from acylcarnitine. this is then translocated via CAT1 and CAT2 transporter system

This step is likely to be the main stenosis limiting the rate of FFA oxidation during exercise

Carnitine is synthesised in the liver and L-Carnitine can be supplemented in the diet

Skeletal muscle [carnitine] is ~ 1 mM

Question 25

What is a role for carnitine?

Answer 25

During steady-state exercise (

Question 26

During sustained aerobic exercise in the moderate or heavy intensity muscular energy provision is almost exclusively derived from?

Answer 26

Oxidative phosphorylation

Question 27

The relative contributions of carbohydrate and fatty acid oxidation are dependent on a number of factors including

Answer 27

nutritional status, exercise intensity, exercise duration, state of training and circulating catecholamines

Of these (in relation to exercise) exercise intensity is probably the most important factor determining the proportion of CHO/FFA oxidation – the higher the relative work rate the greater the CHO contribution

Question 28

Why does the switch from FFA to CHO oxidation with exercise intensity occur?

Answer 28

The switch from FFA to CHO oxidation with exercise intensity allows a higher rate of energy provision from oxidisable substrates (because maximum CHO oxidation rate is ~2x that of FFA), but places a greater strain on the limited muscle glycogen stores

Question 29

What is the mechanism controlling the balance between FFA/CHO oxidation ?

Answer 29

The mechanism controlling the balance between FFA/CHO oxidation is not well known, but may relate to the relative activation of glycolysis (via [citrate], [ADP], [AMP] or [NADH]), or inhibition of mitochondrial fatty acyl CoA transport (via [malonyl CoA] or [carnitine])