01-Metabolism

Energy : 

1 Energy

Energy : 

2 Energy The capacity to do work Many different forms Exchanged between forms and throughout different compounds via chemical reactions In the context of exercise physiology, we are primarily concerned with the conversion of chemical energy to mechanical energy

Energy : 

3 Energy Required by cells of the body Units: kilocalories (kcal); kilojoule (kJ) 1 kcal = 4.184 kJ Where does energy come from? Sunlight Nutrients in plants (photosynthesis)

Energy : 

4 Energy We eat the nutrients (plant and animal sources) Have to convert the energy from the nutrients into a usable form

3 primary nutrients can be broken down and used for energy : 

5 3 primary nutrients can be broken down and used for energy Carbohydrates (CHO) (sugars) Lipids (Fats) Protein Referred to as macronutrients Other nutrients?

Carbohydrates (CHO) : 

6 Carbohydrates (CHO) Made of carbon, hydrogen, & oxygen Exists as: Monosaccharides: glucose, fructose Disaccharides: Sucrose, maltose, lactose Polysaccharides: Glycogen, starch Glycogenesis – synthesis of glycogen from glucose Glycogenolysis – breakdown of glycogen

Fats (lipids) : 

7 Fats (lipids) Made of carbon, hydrogen, & oxygen Several different forms: Fatty acids Triglycerides Phospholipids Steroids

Lipids (Fatty Acids) : 

8 Lipids (Fatty Acids) Long chain of carbons with hydrogens attached (most are 16-18 carbons) Need a protein “carrier” (albumin) to travel in the blood; “free fatty acids”

Lipids (Fatty Acids) : 

9 Lipids (Fatty Acids) Saturated f.a. – no double bonds between carbons Monounsaturated f.a. – 1 double bond Polyunsaturated f.a. - >1 double bond

Lipids (Triglycerides) : 

10 Lipids (Triglycerides) Triglycerides (triacylglycerol): glycerol molecule with 3 fatty acids attached can be metabolized for energy Major storage form of fat (adipose tissue and skeletal muscle) Major form of fat in the diet

Proteins : 

11 Proteins Made of carbon, hydrogen, oxygen, & nitrogen Made up of building blocks called “amino acids” There are approximately 20 different amino acids

Proteins : 

12 Proteins All amino acids have the same structure except for their “side chain” or “R group” Amino acids link together to form proteins (peptide bonds) Dipeptide – 2 a.a. linked together Tripeptide – 3 a.a. linked together

Atwater General Factors : 

13 Atwater General Factors Refers to the net metabolizable energy from ingested nutrients 1 g CHO yields ~4 kcal of energy 1 g lipid yields ~9 kcal of energy 1 g protein yields ~4 kcal of energy *in a healthy person, protein is not a major source of energy at rest or during exercise

Bioenergetics : 

14 Bioenergetics “Energy flow through living systems” Transfer of chemical energy in nutrients to mechanical energy to perform work We need to put the energy from nutrients into a usable form

Adenosine Triphosphate (ATP) : 

15 Adenosine Triphosphate (ATP) Adenine Ribose 3 phosphate groups Capable of receiving/storing energy from nutrients Capable of transferring energy to power biologic work ATP is the “energy currency”

Adenosine Triphosphate (ATP) : 

16 Adenosine Triphosphate (ATP) Energy is stored within the phosphate bonds and released when bonds are broken If 1 phosphate is removed: Adenosine diphosphate (ADP) If 2 phosphates are removed: Adenosine monophosphate (AMP)

ATP hydrolysis : 

17 ATP hydrolysis

ATP hydrolysis : 

18 ATP hydrolysis ATP  ADP + Pi + energy Can be reversed: ADP + Pi + energy  ATP

ATP : 

19 ATP We cannot store a lot of ATP Have enough stored to provide energy for a few seconds of maximal activity We need pathways to resynthesize ATP

Metabolic pathways to regenerate ATP : 

20 Metabolic pathways to regenerate ATP Immediate pathway (phosphagen system) – Creatine phosphate / myokinase no oxygen required (anaerobic) Glycolytic pathway (anaerobic glycolysis) – Fuel: CHO anaerobic Oxidative pathway (aerobic pathway) – Fuels: CHO, fat, or protein oxygen is required (aerobic)

Immediate Pathway : 

21 Immediate Pathway Occurs in cytoplasm Anaerobic Creatine phosphate – ATP (Phosphagen) system CP + ADP  ATP + C Catalyzed by creatine kinase

Immediate Pathway : 

22 Immediate Pathway Adenylate Kinase (Myokinase) reaction ADP + ADP ATP + AMP Catalyzed by adenylate kinase (myokinase) The immediate pathway can fuel maximal intensity activity for up to ~10-15 seconds

Glycolytic Pathway : 

23 Glycolytic Pathway In cytoplasm Can fuel near-maximal activity for 20-90 sec Anaerobic Begins with glucose (6-C) or glycogen Results in: 2-3 ATP and 2 pyruvate (3-C) 2 pyruvate  2 lactate

Glycolytic Pathway : 

24 Glycolytic Pathway Glucose entry into cell Insulin Glucose transporters (GLUTs) GLUT-4: in sk muscle Insulin-dependent GLUT-4 also activated by muscle contraction

Glycolytic Pathway : 

25 Glycolytic Pathway “Glycolysis”

Glycolytic Pathway(Energy Investment Phase) : 

26 Glycolytic Pathway(Energy Investment Phase)

Glycolytic Pathway(Energy Generation Phase) : 

27 Glycolytic Pathway(Energy Generation Phase)

Glycolytic Pathway : 

28 Glycolytic Pathway Assuming insufficient oxygen: +H

Glycolytic pathway : 

29 Glycolytic pathway How many ATP were formed? 4 But 2 ATP were used at the beginning so, A net of 2 ATP ATP formation in glycolysis is termed: Substrate-level phosphorylation ATP is formed without oxygen

Slide 30: 

30

Glycolytic Pathway : 

31 Glycolytic Pathway What if we began with glycogen? Net of 3 ATP

Hydrogen/Electron carriers : 

32 Hydrogen/Electron carriers Hydrogens are frequently removed from substrates and are transferred to carriers Move in pairs Hydrogens are important b/c they carry energy in the electrons (e-) they possess 1 hydrogen atom has 1 proton (H+ ) and 1 electron (e-) 2H = 2 H+ + 2 e- Nicotinamide adenine dinucleotide (NAD) NAD + 2H  NADH+H Flavin adenine dinucleotide (FAD) FAD + 2H  FADH2

Summary of Glycolytic Pathway : 

33 Summary of Glycolytic Pathway Anaerobic Occurs in cytoplasm Begin with glucose or glycogen End result: 2 ATP if began w/glucose 3 ATP if began with glycogen 2 pyruvate molecules (converted to lactate)

Key enzymes associated with glycolytic pathway : 

34 Key enzymes associated with glycolytic pathway Hexokinase: glucose  glucose 6-phosphate Phosphorylase: glycogen  glucose 6-phosphate Phosphofructokinase (PFK): rate-limiting enzyme

Oxidative Pathway (CHO) : 

35 Oxidative Pathway (CHO) Begin with glucose or glycogen Get 2-3 ATP If sufficient oxygen is available, most pyruvate is not readily converted to lactate!!!

Oxidative Pathway (CHO) : 

36 Oxidative Pathway (CHO) Pyruvate (3-C) enters mitochondrial matrix Carrier protein Pyruvate is converted to: Acetyl-CoA (2-C) Pyruvate dehydrogenase facilitates this reaction NAD is reduced to NADH+H

Oxidative Pathway : 

37 Oxidative Pathway Acetyl-CoA (2-C) enters Kreb’s (TCA; citric acid) cycle Occurs in mitochondrial matrix

Kreb’s Cycle : 

38 Kreb’s Cycle Kreb’s cycle intermediates

Kreb’s cycle products : 

39 Kreb’s cycle products Remember there were 2 pyruvate from each glucose Thus for each molecule of glucose: 2 ATP (GTP  ATP) 6 NADH+H 2 FADH2 4 CO2 2 oxaloacetate So what???

Electron Transport Chain : 

40 Electron Transport Chain Series of electron carriers (cytochromes) and proton pumps on the inner mitochondrial membrane Oxygen is at the end

Electron Transport Chain : 

41 Electron Transport Chain NADH+H and FADH2 enter ETC 2 electrons are removed from each pair of H’s Electrons flow down the ETC toward oxygen Protons (H+) are pumped into the intermembrane space as the electrons flow down the ETC

Electron Transport Chain : 

42 Electron Transport Chain As H+ build up in intermembrane space, an electrochemical gradient is formed

Slide 43: 

43

Electron Transport Chain : 

44 Electron Transport Chain H+ flow back into the matrix via “ball-and-stalk complexes” or “respiratory assemblies” that have the enzyme: ATP synthase The H+ flowing into the matrix provide energy to produce ATP from ADP and Pi ATP is formed using the energy associated with the protons (H+) flowing back to the matrix Oxidative Phosphorlylation

Electron Transport Chain : 

45 Electron Transport Chain Remember: since NADH+H entered the ETC at an earlier point than FADH2: More H are pumped across More H flow back to matrix More ATP are formed Each NADH+H = ~2.5 ATP Each FADH2 = ~1.5 ATP

Slide 46: 

46

Figure 3.11 : 

47 Copyright © Pearson Education, Inc. publishing as Benjamin Cummings Figure 3.11

Fat Metabolism : 

48 Fat Metabolism Triglycerides → glycerol + 3 f.a. (lipolysis; enzyme = lipase) F.A. are transported through the blood via albumin F.A. enter cell via transporters Carnitine transports fatty acids into mitochondrial matrix Beta-Oxidation occurs in matrix

Fat Metabolism : 

49 Fat Metabolism

Beta-Oxidation : 

50 Beta-Oxidation series of reactions that cleaves 2-carbon units during each cycle 2-carbon unit is released as Acetyl-CoA NADH+H & FADH2 are also released Example: 16-C f.a. 14-C f.a. + Acetyl-CoA + NADH+H + FADH2 14-C f.a. 12-C f.a. + Acetyl-CoA + NADH+H + FADH2 …. Repeats until only a 2-C unit (acetyl-CoA) is left

Beta-Oxidation : 

51 Beta-Oxidation

ATP Tally from Fat : 

52 ATP Tally from Fat The length of the fatty acid is directly related to the amount of ATP that can be generated Ex: 16-carbon f.a. ~130 ATP 18-carbon f.a. ~146 ATP

Protein Metabolism : 

53 Protein Metabolism Not usually a major fuel source Break into amino acids Remove amino (N-containing) group The remaining “carbon-skeleton” is used for energy

Fate of carbon skeleton : 

54 Fate of carbon skeleton Glucogenic aa: Glucose, pyruvate, Krebs intermediates Ketogenic aa: Acetyl-CoA

Oxidative Pathway : 

55 Oxidative Pathway The oxidative (aerobic) pathway becomes the primary energy system during low-intensity activity and high-intensity activity that lasts >~2 min The relative contribution of CHO, fat, and protein depend on intensity and duration

Gluconeogenesis : 

56 Gluconeogenesis Formation of glucose from 3-C precursors Glycerol (glycerol-glucose cycle) Pyruvate / Lactate (Cori cycle) Alanine (glucose-alanine cycle)

Gluconeogenesis : 

57 Gluconeogenesis glycerol-glucose cycle Cori cycle glucose-alanine cycle

Metabolic Mill : 

58 Metabolic Mill

Slide 59: 

59

Ketones : 

60 Ketones When CHO are low: Oxaloacetate (OAA) → pyruvate → glucose Insufficient OAA to combine with acetyl-CoA OAA + acetyl CoA→ citrate Liver converts acetyl-CoA to ketones Beta-hydroxybutryic acid, acetone, acetoacetic acid Implications? ketones

Key hormones related to metabolism : 

61 Key hormones related to metabolism Insulin:  glucose, fatty acid, and amino acid uptake/  blood glucose Glucagon:  glucose and fatty acid mobilization & gluconeogenesis /  blood glucose Growth hormone: Helps maintain blood glucose Gluconeogenesis Fatty acid mobilization Reduced glucose uptake Catecholamines (epinephrine & norepinephrine):  glycogenolysis & lipolysis Thyroid hormone:  metabolic rate & fuel mobilization