G

Introduction to Macronutrients and Glycolysis

Review from Tuesday's Lecture

  • Three Major Macronutrients and their Kilocalorie Values:

    • Protein: $4$ kcal/g

    • Carbohydrates (Carbs): $4$ kcal/g

    • Fat: $9$ kcal/g

  • Substrates: The actual molecules used for activity, also referred to as the mass action effect, which refers to the amount of substrate's effect.

  • Rate-Limiting Enzyme in the PCR System: Creatine kinase. This enzyme catalyzes the phosphocreatine (PCR) system.

  • Importance of Negative Feedback for Regulating Metabolic Pathways:

    • Prevents Waste: ATP is a crucial energy source; negative feedback ensures energy and resources are not wasted.

    • Maintains Homeostasis: Ensures energy production matches demand, preventing overproduction.

    • Protects Against Overproduction of Harmful Byproducts: Some pathways can produce excessive hydrogen ions, altering pH and potentially leading to toxic levels of byproducts. Negative feedback limits this.

    • Quick Responsiveness: Essential for frequent changes in energy demand.

    • The rate-limiting enzyme works in conjunction with negative feedback.

  • Anaerobic Systems: Do not use oxygen.

  • ATP-PCR System:

    • Main Fuel Source: Phosphocreatine (PCr).

    • Duration of High-Intensity Exercise: Approximately 3 to 15 seconds. It acts as an immediate, backup energy source, similar to a phone's portable charger.

    • Yield Ratio: 1:1 (one PCr yields one ATP), making it readily and quickly available.

General Reminders

  • Real assignment due on Sunday.

  • Quizzes moved to Mondays before class to align with Tuesday reviews.

  • Next exam is approaching, covering anaerobic systems, energy expenditure, and hormonal control.

Anaerobic Glycolysis

  • Definition: The breakdown (lysis) of glucose through a pathway involving a sequence of enzymes.

  • Glycogenolysis: The breakdown of liver glycogen into glucose. Glycogen is the stored form of glucose, like bulk cereal at a store that gets individually packaged.

  • Fuel Sources: Digestion of carbohydrates and breakdown of liver glycogen turn into glucose. Glucose constitutes about 99\% of circulating blood sugar.

  • Duration: This system takes over from the ATP-PCR system, fueling activities from approximately 15 seconds to 2 minutes (e.g., a 400-meter dash).

  • Process Overview: Anaerobic glycolysis breaks down glucose or glycogen into pyruvate, which is then converted into lactate. It produces a small, rapid amount of ATP, quicker than oxidative phosphorylation but slower than PCR.

  • Location: Occurs in the cytoplasm of the cell, outside the mitochondria.

Steps of Glycolysis

  • General Principle: All metabolic systems and functions require enzymes to catalyze reactions.

    • Creatine kinase is for PCR.

  • Step 1: Phosphorylation of Glucose/Glycogen:

    • Both glucose and glycogen must be converted into glucose-$6$-phosphate (G6P).

    • Enzyme for Glucose: Hexokinase (often the first enzyme and can be rate-limiting).

    • Energy Cost (Glucose): This step costs 1 ATP to convert glucose to G6P.

    • Energy Cost (Glycogen): Glycogen bypasses this initial ATP cost, directly forming G6P without using an ATP at this step.

    • This initial ATP usage to make more ATP later is a form of negative feedback.

  • Step 2: Isomerization to Fructose:

    • Glucose (specifically G6P) is rearranged into fructose.

    • Enzyme: G6P isomerase. Isomerases transform the structure of a molecule without changing the number of atoms, aligning them for easier metabolism.

  • Step 3: Second Phosphorylation (PFK Step):

    • Fructose-$6$-phosphate is converted into fructose-$1,6$-bisphosphate.

    • Enzyme: Phosphofructokinase (PFK).

    • Energy Cost (Glucose & Glycogen): This step costs 1 ATP for both pathways.

    • PFK as the Rate-Limiting Enzyme for Anaerobic Glycolysis: While hexokinase is first, PFK is generally considered the primary rate-limiting enzyme for glycolysis. It doesn't always have to be the first enzyme, just an early, controlling one.

    • Regulation of PFK Activity:

      • Enhancement: Increased ADP and phosphate concentrations (indicating a need for ATP) enhance PFK activity.

      • Inhibition: Increased ATP concentration (indicating sufficient energy) inhibits PFK activity – a negative feedback loop.

  • Steps 4-10: Energy-Creating Steps:

    • Fructose-$1,6$-bisphosphate is split into two 3-carbon pieces.

    • Each carbon phosphate group is eventually converted into pyruvate.

    • Yield During these Steps:

      • 2 NADH (which will go to the electron transport chain later).

      • 4 ATP (total).

      • 2 Pyruvate.

Summary Net Yield of Glycolysis

  • Reaction Steps: 10 to 12 steps, all occurring in the cytoplasm.

  • From Glucose:

    • Gross ATP: 4

    • ATP Invested: 2

    • Net ATP: 2

    • 2 NADH

    • 2 Pyruvate

    • Enzymes: Hexokinase (initial), PFK (rate-limiting).

  • From Glycogen:

    • Gross ATP: 4

    • ATP Invested: 1

    • Net ATP: 3

    • 2 NADH

    • 2 Pyruvate

    • Enzymes: PFK (rate-limiting).

Fate of Pyruvate

  • Glycolysis (anaerobic) produces pyruvic acid (pyruvate) and does not require oxygen.

  • In Absence of Oxygen (Anaerobic): Pyruvate is converted into lactate (lactic acid).

  • In Presence of Oxygen (Aerobic): Pyruvate proceeds to aerobic metabolism (oxidative phosphorylation), which is a different fate.

  • Transition Factors: Substrate availability and enzyme activity, rather than strict time cutoffs, determine which system is used, though time and intensity do play a role in energy demand. Systems are always transitioning and rarely have strict on/off points.

Analogy for Energy Systems (Wall Sit)

  • Initial Squat/Contraction: ATP-PCR system kicks in (immediate, powerful).

  • Continued Hold: Glycolysis takes over (maintains contraction, but burning sensation starts due to lactate and hydrogen ion accumulation).

  • Longer Hold (e.g., 30+ seconds): Requires increased oxygen intake as muscles transition to aerobic metabolism.

Lactic Acid/Lactate

  • Buildup: Lactate buildup, along with hydrogen ions, changes pH, leading to the burning and soreness sensation in muscles during intense activity.

  • It's not solely lactic acid but a combination of factors, including hydrogen ions, that alter pH.

Pros and Cons of Glycolysis

  • Pros:

    • Allows muscles to contract when oxygen is limited.

    • Provides energy for longer-term, higher-intensity exercise than the PCR system.

    • Lactate can be used as an energy source later.

  • Cons:

    • Low ATP yield (net 2 or 3 ATP).

    • Lack of oxygen converts pyruvate to lactic acid (lactate).

    • Lactic acid buildup can impair further glycolysis and muscle contraction, leading to muscle soreness.

Review Questions (Self-Assessment)

  • Does anaerobic glycolysis need oxygen? No.

  • How long can anaerobic glycolysis fuel exercise? Approximately 15 seconds to 2 minutes.

  • What is the main fuel source (substrate) for anaerobic glycolysis? Glucose or Glycogen.

  • Note on Substrates: Macronutrients (carbs, fats, proteins) are what we intake, while substrates (glucose, glycogen, free fatty acids, amino acids) are the broken-down forms our bodies use for energy.

  • What enzyme regulates PCR? Creatine kinase.

  • Where does anaerobic glycolysis take place within the cell? Cytoplasm.

  • What is the rate-limiting enzyme for anaerobic glycolysis? PFK (Phosphofructokinase).