1. KIN 392/393 Physiology of Exercise Dr. Kraemer Slides for Chapter 3/4

2. ATP production Specifics - Aerobic tally  33 ATP are produced from the complete breakdown of glucose from glycogen. 32 ATP are produced if it comes from blood glucose. 1.Three (or 2 from blood glucose) net ATPs result from substrate phosphorylation in glycolysis. 2. Two ATPs result from substrate phosphorylation in the Krebs Cycle. 3. 28 ATP from oxidative phosphorylation of NADH from glycolysis and the Krebs Cycle and from FADH from the Krebs Cycle.

4.  The rate of ATP production in the biochemical pathways is controlled to meet energy demand  If enough substrate is available, an increase in the number of enzymes present causes an increased rate of chemical reaction.  Thus, if you regulate 1 or more of the enzymes in biochemical pathways, you can control the rate of ATP production.  Rate-limiting enzymes are found in metabolic pathways. They control the "speed" of a metabolic pathway.

6.  Since activity such as sprinting requires energy production at a rate greater than 100% of resting energy production, rate- limiting enzymes become very important.  How do they work? –They are typically located near the beginning of a metabolic pathway. Thus, they can increase the amount of a product to be further broken down. –Modulators act on the rate-limiting enzyme causing it to increase or decrease the rate of enzyme activity.

7. –  ADP   rate-limiting enzyme activity –  ATP   rate-limiting enzyme activity Control of the phosphagen system Control of the phosphagen system   ADP and  ATP increases activity of creatine kinase.   ADP and  ATP decreases activity of ck.

8. –Other Factors  Two important factors that influence enzyme activity are body temperature and pH.  Increasing body temperature above normal (37 C) increases activity of most enzymes  Increasing body pH of body fluid also increases enzyme activity – See figures

11. Control of Glycogenolysis Control of Glycogenolysis  The major rate limiting enzyme is phosphorylase.  Phosphorylase catalyzes the breakdown of glycogen to glycose-1-phosphate in glycogenolysis.  This increases the amount of G-1-P produced which, in turn, increases the amount of G-6-P produced which increases the rate of glycolysis.  Epinephrine (Epi) and Ca 2+ increases phosphorylase activity (converts phosphorylase b into phosphorylase a, Ca 2+ acts through calmodulin, Epi acts through cyclic AMP).

14. Control of Glycolysis Control of Glycolysis  The major rate limiting enzyme is phosphofructokinase (PFK) PFK PFK – fructose-6-phosphate  fructose 1,6 biphosphate Control of the Krebs cycle Control of the Krebs cycle  Isocitrate dehydrogenase is the major rate-limiting enzyme. isocitrate dehydrogenase isocitrate dehydrogenase  Isocitrate -ketoglutarate

16.   ADP/Pi   isocitrate dehydrogenase activity   Krebs cycle activity   ATP   isocitrate dehydrogenase activity   Krebs cycle activity Control of Electron Transport Chain Control of Electron Transport Chain  Cytochrome oxidase (cytochrome 6) is the major rate limiting enzyme for the ETC.  ADP/Pi   ETC activity.  ATP   ETC activity.

18. Fat metabolism  Fats are burned during exercise. A majority of the energy comes from the breakdown of fatty acids that are mobilized from adipocytes. –Hormone sensitive lipase (HSL), an enzyme in adipose sites, catalyzes the breakdown of triglycerides into glycerol and 3 fatty acid molecules. –Fatty acids circulate in the blood to skeletal muscle and go to the mitochondria of skeletal muscle where they are broken down.

20. –They first go through beta- oxidation in mitochondria:  A fatty acid is activated with ATP.  The fatty acid goes through 3 reactions. An NAD and an FAD are required.  Two carbon atoms are cleaved off the fatty acid molecule for each turn of ß- oxidation, coenzyme A is combined to make acetyl CoA. The rest of the activated fatty acid goes through ß-oxidation. Stearic Acid Stearic Acid

23.  Acetyl CoA goes through the Krebs Cycle and the H 2 's go through the ETC.  (See example for different size fatty acid molecules.)  During exercise several stimulators/inhibitors or other factors affect HSL, which affects the amount of fat used. (from adrenals & pancreas α-cells) –Exercise   Epi   HSL activity   FFA mobil.   FFA glucagon catabolism (Epi figure, 60%VO 2 max)

26. – duration of exercise  insulin levels   HSL activity   FFA mobilization   FFA catabolism (insulin figure, 60%VO 2 max)   insulin with exercise is due to  catecholamines –exercise intensity   lactic acid   HSL activity →  FFA mobilization  FFA catabolism  Lactic acid is an inhibitor of HSL

28. –Consume high CHO meal 30-60 min (Powers) before exercise   insulin levels in 15-30 min   HSL activity →  FFA mobilization  FFA catabolism.   reliance on CHO reduces glycogen stores.  Insulin glycolysis by increasing the uptake of glucose in cell and increasing the formation of fats which decreases the availability of FFA as substrate.

30. Glucagon responses to exercise at 60% of VO 2 max

39. Interaction of Fat/CHO metabolism Interaction of Fat/CHO metabolism  Fats burn in a carbohydrate flame  When there is depletion of CHO it not only reduces CHO catabolism but it reduces FFA catabolism. – Pyruvic acid is in equilibrium with oxaloacetic acid. – glycolysis   levels of pyruvic acid in the sarcoplasm – Pyruvate carboxylase converts oxaloacetic acid into pyruvic acid when pyruvic acid levels are low.

40. pyruvate carboxylase oxaloacetic acid  pyruvic acid oxaloacetic acid  pyruvic acid – This reduces FFA catabolism because there isn't enough oxaloacetic acid to accept acetyl CoA from -oxidation. – Thus, fats burn in a carbohydrate flame.  Whether fat or CHO is the primary substrate during exercise is determined by: –Availability of the fuel to muscle –Factors that regulate glycolysis, the Krebs cycle, & the ETC.

41. – CHO's are the primary fuel in short-term intense (but > 10s) exercise. – CHO's are the major fuel at the onset of low to moderate exercise.

42. –During low to moderate exercise there is a slow shift from CHO toward fat. (crossover effect for duration)  Mechanisms Gradual increase in norepinephrine, epinephrine (Epi), & glucagon over time Gradual increase in norepinephrine, epinephrine (Epi), & glucagon over time Gradual decline in insulin Gradual decline in insulin Gradual increase in citrate that inhibits PFK – With more FA to acetyl CoA in Beta- Oxidation there is more citrate produced in the Krebs Cycle. Gradual increase in citrate that inhibits PFK – With more FA to acetyl CoA in Beta- Oxidation there is more citrate produced in the Krebs Cycle.

45. Exercise at 65 – 75% VO 2 max

46. –During graded exercise from low to high intensity there is a shift from fat to CHO (crossover effect for intensity).  Mechanisms –Increase in lactic acid that is a more potent inhibitor than Epi and norepinephrine are stimulators –Increase in ADP stimulates PFK (in glycolysis) and increases in Epi and calcium to stimulate phosphorylase

51.  There is a myth that you have to exercise at low intensities to burn fat. –Even though a lower percentage of the total kcals come from fat than CHO at high intensities, it is possible to burn the same total number of fat kcals at a higher exercise intensity compared with at lower exercise intensity.  The reason is at higher intensities you burn more total kcals, so you use a lower percentage (fat) of a higher total.

53. Protein Utilization During Exercise  Any factor that increases the pool of amino acids in skeletal muscle or in the liver can increase protein metabolism. –Prolonged exercise (> 120 min) can do this. Protease activity is increased after long-term exercise (Dohm et al.) causing an increase in amino acid catabolism.

54. – –Thus, amino acids may be used to fuel exercise. – –Studies of amino acid utilization have found up to 10% of the energy for exercise may come from protein. – –When protein intake does not equal protein breakdown, there is a negative nitrogen balance (N-balance). – –The ability to maintain N-balance during exercise is dependent on a number of factors:

55. – –Training status of the subject – –Quality and quantity of protein consumed – –The total calories consumed – –The body’s carbohydrate stores – –The intensity, duration, and type (resistance versus endurance) exercise   If measurements of protein utilization are made during the first few days of an exercise program, formerly sedentary subjects have a negative N-balance the first few days of the program. – –After 12-14d of training, this condition disappears and a person usually can maintain N-balance

57. – –One of the ways that protein is used during exercise is the glucose- alanine cycle.   The glucose-alanine cycle involves transamination of the amino group of leucine (or isoleucine or valine) to pyruvate in skeletal muscle.   The remaining carbon skeleton of the amino acid can be converted into a Krebs Cycle substrate and used to make ATP   The alanine is circulated to the liver where it is deaminated, making urea and becoming pyruvate again.

59. Amino Acid

60. Gluconeogenesis

61.   Pyruvate goes through gluconeogenesis to become glucose and then can be released as blood glucose to circulate back to the muscle.   Glucose can be used by the skeletal muscle to make ATP for exercise. – –After 4 h of continuous light exercise, the liver’s output of alanine- derived glucose accounts for about 45% of the liver’s total glucose release. – –During long-term exercise, the glucose-alanine cycle may generate 10- 15% of the total exercise energy requirement.