KPE264 - Module 2

• Several energy systems supply ATP at different rates and durations, depending on the activity.

Sarcolemma and Energy Systems

• ATP is converted to ADP in the cytosol near the sarcolemma
• Phosphagen occurs in the cytosol, utilizing 1 reaction
• Glycolytic occurs in the cytosol, utilizing 10 reactions
• Oxidative occurs in the mitochondria, utilizing greater than 10 reactions

Energy Systems: Rate vs Duration

• Phosphagen:
  • Produces more ATP
  • Availability is limited
• Glycolytic:
  • Can be relied on for a longer period
• Oxidative:
  • Operates over a longer time period

Phosphagen Stores

• Phosphocreatine "buffers" decreases in ATP immediately.
• The process is instantaneous, but the substrate is quickly depleted, limiting continuous use.
• Only one unit of ATP is formed per unit substrate; burns quickly.

Phosphocreatine: Immediate Energy

• Creatine comes from meat consumed.
• Buffers decline with ATP
• It's close to the site of ADP accumulation in the cytosol
• Reliance is limited over a long period.
• ATP converts to Adenosine with 3 phosphates
• PCr converts to creatine with 1 Phosphate
• Creatine Kinase facilitates the movement between PCr + ADP and ATP + Cr

Reliance on Phosphagen Stores

• Rely on phosphagen stores during:
  • First 15 seconds of intense/forceful movements.
  • "Rest-to-work" transitions.
  • Workload transitions during exercise.
• It takes 5-10 minutes to replenish phosphagen stores.

Creatine Supplementation

• Basic theory: increased Cr + ATP leads to ADP + PCr.
• 90% of creatine storage is in skeletal muscle.
• Supplementation may work in some cases, particularly for those who rely on the PCr system, in brief, intense, repeated exercise and for older adults.
• Problems include:
  • Weight gain.
  • Fluid balance issues; supplement may cause water retention in muscles.
  • Creatine may end up somewhere else other than the muscles.

Non-Oxidative Glycolysis

• Involves a partial breakdown of glucose/glycogen without oxygen.
• Process is rapid but limited by metabolic by-products.
• It generates 2-3 units of ATP per unit of substrate.

Carbohydrate Fuels: Glucose & Glycogen

• Glucose has the chemical formula C6H12O6.
• Glycogen is a glucose polymer.

Glucose and Glycogen Catabolism

• Glycolysis involves the breakdown of one glucose molecule to form two pyruvate molecules.
• Glycogenolysis involves the breakdown of one "glucose unit" (6-C) from glycogen to glucose-1-phosphate.

"Glycolytic System": Key Points

• GLUT transporter allows glucose into the muscle during exercise.
• Hexokinase traps glucose in the muscle.
• Phosphofructokinase (PFK) is a key enzyme.
• Substrate-level phosphorylation generates ATP in the absence of oxygen.
• NADH is an important high-energy substrate used in the ETC to generate ATP.
• Net ATP gain is:
  • 2 for glucose
  • 3 for glycogen
• The liver can take G6-P into glucose.

Fate of Pyruvate

• Pyruvate can turn into lactate:
  • Via lactate dehydrogenase (LDH).
  • This process is anaerobic.
  • NAD is essential to continue glycolysis.
• Pyruvate can turn into acetyl CoA:
  • Via pyruvate dehydrogenase (PDH), which is an enzyme.
  • This process is oxidative.
  • Occurs in mitochondria.

Lactate Formation from Pyruvate

• Lactate formation from pyruvate regenerates NAD.

Reliance on Non-Oxidative Glycolysis

• Heavily relied on during:
  • Intense exercise.
  • "Rest-to-work" transition.
  • Workload transitions in exercise.

Increased Lactic Acid

• Increased lactic acid can be a potential problem due to the buildup of H+.
• H+ significantly affects muscle pH.
• Leads to a decrease in muscle pH resulting in:
  • Metabolic inhibition, decreasing enzyme activity and the ability to continue the pathway, as H+ interferes with PFK.
  • Contractile inhibition, decreasing crossbridge cycling and interfering with actin & myosin, which reduces efficiency in crossbridge formation.

Lactate as a Fulcrum

• Lactate anion is formed under fully aerobic conditions.
• Major source for mitochondrial respiration.
• Functions as a major gluconeogenic precursor and signaling molecule.
• Stimulates mitochondrial growth.

Oxidative Metabolism

• Involves a complete breakdown of CHO, fats, and AAs to CO2 and H2O.
• Strips all potential energy from carbs & fats for efficient energy use.
• Requires oxygen for sustained energy.
• Essential processes occur in the mitochondrion.
• Generates over 30 units of ATP per unit substrate.

Mitochondria

• The powerhouse of the cell.
• H+ is pumped across the intermembrane.

Oxidative Metabolism: Essential Steps

• Formation of acetyl CoA from CHO, fat, or AA.
  • It is universal and comes from any substrate.
• Oxidation of acetyl CoA (Krebs cycle).
  • Coenzymes are reduced.
    • NAD+
    • FADH
  • Loss of electron - oxidize
  • Gain of electron - reduction
• Formation of ATP via the electron transport chain:
  • Coenzymes are oxidized.
  • Complexes in the ETC are reduced.
• It's hard to do during high intense exercise.

Carbohydrate Oxidation

• Pyruvate + NAD converts to acetyl coA + CO2 + NADH, using pyruvate dehydrogenase.
• In the absence of oxygen, the fate of pyruvate is lactic acid.
  • Pyruvate dehydrogenase is an enzyme in mitochondria.
• NADH is:
  • Used in oxidative phosphorylation.
  • Found in glycolysis and used in the ETC.
• During anaerobic conditions, NADH oxidizes to NAD, and lactate regenerates NAD.

Krebs Cycle/TCA/Citric Acid Cycle

• More NADH is generated, leading to 3 ATP in the ETC.
• FADH2 is generated, leading to 2 ATP in the ETC.
• ATP is also generated.
• Citrate synthase is used.

Electron Transfer: Oxidation & Reduction

• Oxidation involves the loss of electrons.
• Reduction involves the gain of electrons.
• The electron transport chain carries electrons as H atoms.

Electron Transport Chain

• Involves a series of oxidation-reduction reactions.
• Electrons are passed from NADH and FADH2 to O2.
• Cytochrome oxidase transfers H+ to O2 to create H2O.
• ATP synthase facilitates the generation of ATP at the end of the ETC.

Oxidative Phosphorylation

• Generation of ATP is due to movement of H+ ions across the membrane.
• Accounting for transport of ATP:
  • NADH = 2.5 ATP
  • FADH2 = 1.5 ATP

Maximum Aerobic ATP Yield

• The values shown are for starting with 1 x 6-C “glucose unit” cleaved from glycogen:
  • Glycolysis: 3 ATP (total if anaerobic), 2 NADH.
  • Pyruvate dehydrogenase reaction: 2 NADH.
  • TCA/ETC: 6 NADH, 2 FADH2, 2 ATP.

Fat Oxidation - Triglyceride Structure

• Main sources are adipose tissue and skeletal muscle.
• The basic structure contains glycerol.

Stages of Lipid Catabolism

1. Mobilization – TG breakdown (“lipolysis” in adipose tissue/muscle
2. Transport – FA in blood via albumin to skeletal muscle
3. Uptake – FA enters muscle cytosol
4. Activation – FA “prepared” for breakdown by mitochondria
5. Uptake - FA enters mitochondria
6. Beta-oxidation – FA is broken down in mitochondria
7. Mito oxidation – TCA cycle/ETC activity

FA Mobilization

• Hormone-sensitive lipase (HSL) stimulates this and is stimulated by:
  • Lack of glucose.
  • Hormones (epi/norepinephrine).
  • Cortisol increasing HSL
  • Insulin shuts off HSL
• 3 FAs turn into the muscle to catabolize for energy
• Glycerol turns into Liver converted to glucose

FA Transport, Uptake & Activation

• Fatty acetyl-CoA is recognizable by mitochondria.
• Carnitine palmitoyl transferase (CPT) shuttles FA to mitochondria in order to activate.
• Carnitine (acts as an escort):
  • Is a Key component of CPT
  • Without this, cannot use Fatty Acids for energy
  • Becomes unavailable during high intense exercise

Carnitine as a Weight Loss

• Carnitine does NOT work.
• The supplement wants to end up in Mitochondria tissues of interest

Beta Oxidation

• Key points:
  • Key step Before TCA
  • 2c become an acetyl-coa goes through B-oxidation
  • Goes through 7x remain final 2C
  • Number of Carbons divided by 2-1

ATP Yield

• Each "Turn" of B-oxid requires
  • 1 FADH- 1.5 ATP
  • NADH- 2.5 ATP
  • 1 Acetyl-COA requires 10 ATP
  • Remaining 2C unity

Performance

• If CHO isn't used as a substrate, for elite athlete performance, during events longer than 30s-4 hours, there may be decreased performance

Protein Metabolism - Breakdown

• AA are used as fuel by - removing amino group
  • Major site- Liver
  • Minor Site- Skeletal muscle
• Oxidation of remaining “Carbon Skeleton” (“oxo acid”) - Eventually from Pyruvate or Acetyl COA
• Major AA in Exercise - BCAA (Leucine, Isoleucine, Valine) - Alanine, Glutamine
• *Draw out BCAA example

Gluconeogenesis : Recycling

• Gluconeogenesis — formation of “New Glucose” from metabolic Intermediates