Metabolism, ATP and Energy Production

Module 7: Metabolism Learning Objectives

• Describe the structure and function of ATP (adenosine triphosphate).
• Compare the meaning of metabolism, catabolism, and anabolism.
• Briefly describe glycogenesis, glycogenolysis, and gluconeogenesis.
• Describe the role of coenzymes NAD+ and FAD in cellular oxidation reactions.
• Explain the difference between substrate-level phosphorylation and oxidative phosphorylation.
• Summarize the important events and products of the ATP-producing pathways (phosphagen system, glycolysis, Krebs cycle, and electron transport chain).
• Describe how fats are oxidized for energy.
• Explain when and why ketones are formed.

Adenosine Triphosphate (ATP)

• ATP is the main energy source for humans.
• When energy is needed, a phosphate group is broken off from ATP.
• This process releases energy that the body can use.
• ATP is adenosine triphosphate and has 3 phosphate groups.
• ADP is adenosine diphosphate and has 2 phosphate groups.

Important Terminology

• Metabolism is the sum of chemical reactions occurring in the body cells.
• Catabolism is the breakdown phase of metabolism where complex substances are broken down into simpler substances which releases energy.
• Anabolism is the building phase of metabolism where simple substances are combined to form more complex substances which requires energy.
• Glycogenesis is the formation of glycogen from glucose.
• Glycogenolysis is the breakdown of glycogen to glucose.
• Gluconeogenesis is the formation of glucose from non-carbohydrate molecules.

Stages of Metabolism of Energy-Containing Nutrients

• Stage 1 (GI Tract):
  • Nutrients are digested into absorbable units.
  • Nutrients are absorbed into the blood and transported to tissue cells.
• Stage 2 (Tissue Cells):
  • Anabolism involves nutrients being built into macromolecules.
  • Catabolism involves nutrients being broken down to pyruvic acid and acetyl CoA.
  • Glycolysis is the major catabolic pathway.
• Stage 3 (Mitochondria):
  • Stage 2 products undergo oxidative breakdown.
  • CO₂ is released.
  • Hydrogen atoms removed are delivered to molecular oxygen, forming water.
  • Some of the released energy is used to form ATP.
  • The citric acid cycle and oxidative phosphorylation are major pathways.

Coenzymes in Cellular Oxidation Reactions

• NAD+ and FAD are energy carriers.
• They pick up released electrons from glucose molecules.
• Electrons from these carriers are released during cellular oxidative reactions, releasing energy to generate ATP.

Substrate-Level vs. Oxidative Phosphorylation

• Phosphorylation involves adding phosphate to an organic compound (e.g., ADP + P → ATP).
• Substrate-level phosphorylation directly phosphorylates ADP with a phosphate group, using energy released from a bond and not necessarily requiring O2.
• Oxidative phosphorylation relies on NAD+ and FAD to carry electrons to the electron transport chain, uses ATP synthase, and requires O2.

Methods of Phosphorylation

• In substrate-level phosphorylation, a molecule donates a phosphate to ADP, forming ATP.
• Oxidative phosphorylation uses ATP synthase to combine phosphate with ADP, forming ATP.

Energy System Pathway Overview

• ATP producing pathways can be anaerobic or aerobic
• Anaerobic pathways include:
  • ATP-CP
  • Glycolysis
• Aerobic pathways include:
  • Krebs Cycle
  • Electron Transport Chain

Phosphagen System (ATP-CP System)

• It is also known as the phosphocreatine system or ATP-PCr system.
• This system is anaerobic and occurs in the cytoplasm.
• It produces ATP the fastest.
• It supports very brief, high-intensity activities lasting 3-15 seconds.
• This system involves creatine phosphate (CP aka PCr) as a substrate.
• Within ~2 minutes of recovery, CP is restored.
• This process depends on a healthy aerobic system, where mitochondria needs O₂ to make ATP to restore CP stores.
• CP is the limiting factor in this reaction.

Glycolysis

• Glycolysis breaks down glucose to make ATP.
• The purpose is to generate ATP.
• Glycolysis does not require oxygen.
• Glucose goes into glycolysis, and pyruvic acid x2 comes out.
• Four ATP are produced during glycolysis but the net is 2.
• Two NAD+ are reduced to form 2 NADH.
• If enough oxygen is available, pyruvic acids go to the Krebs Cycle.
• If oxygen is not available, the end-product of glycolysis is converted to lactic acid, then to lactate and H+.
• Glycolysis uses substrate level phosphorylation to make ATP.

Glycolysis Phases

• Sugar activation ("investment stage"):
  • Glucose is phosphorylated to give it energy for the breakdown process
• Sugar cleavage ("double your money"):
  • The partially processed sugar splits in half, forming two molecules ready for oxidation
• Sugar oxidation/ATP formation ("reap the rewards"):
  • Sugars are oxidized and used to make ATP with a loss of electrons and H+ being added to NAD+
• Final products consist of:
  • pyruvic acid
  • ATP
  • NADH + H+
• If oxygen is available, pyruvic acid is sent to the Krebs Cycle
• If oxygen is not present, pyruvic acid is converted to lactic acid

Citric Acid (Krebs) Cycle

• Pyruvic acid goes into the Krebs Cycle.
• The initial substrate of the Krebs Cycle comes from the end-product of glycolysis.
• It is a cycle, so the carbon-based molecule never really leaves.
• For every pyruvic acid molecule, 1 ATP is produced (=2 ATP per glucose molecule).
• Three NAD+ are reduced to 3 NADH + 3H+, and 1 FAD to FADH2.
• Carbon dioxide is created by this cycle.
• The Krebs Cycle requires oxygen indirectly.
• Its major purpose is to produce electron carriers for the ETC to generate more ATP.

The Citric Acid (Krebs) Cycle

• Occurs in the matrix (middle) of the mitochondria.
• It consists of an 8-step process.
• Products include:
  • ATP
  • NADH + H+
  • FADH2
• Considered an aerobic process, but it does not directly use O₂.
• The ETC uses O₂ and the Krebs cycle stops if the ETC is not working
• The Krebs cycle only occurs in the presence of O₂.

Electron Transport Chain (ETC)

• The main purpose is to create a proton gradient, building up a concentration of protons outside of the mitochondria.
• When protons return into the mitochondria, their energy generates ATP.
• NADH and FADH2 enter the ETC.
• About 30 ATP are produced.
• ETC uses oxidative phosphorylation to make ATP and requires oxygen.

Fat Oxidation

• Lipolysis separates fatty acids from glycerol.
• Glycerol is converted into molecules that enter glycolysis to produce ATP.
• Beta-oxidation breaks down fatty acids.
  • It doesn't make a lot of ATP directly, but it produces NADH and FADH2.
  • The products of this process go to the electron transport chain.

Ketones

• When glucose levels are low, triglycerides are broken down and oxaloacetic acid in converted to glucose.
• More fatty acid breakdown results in excess Acetyl CoA to go through the Krebs Cycle.
• Step 1 of the Krebs Cycle requires oxaloacetic acid to join with Acetyl CoA.
• However, oxaloacetic acid is being used for gluconeogenesis.
• Without oxaloacetic acid, Acetyl CoA builds up.
• The liver converts Acetyl CoA into ketones.

Ketones For Energy

• Some tissues (heart, kidneys, brain) use ketones for energy production.
• This is the body going into "starvation mode", body chemistry is thrown off, but survival is extended.
• A large amount of ketones in the body can make the body acidic, which is dangerous for diabetics.
• The body tightly controls pH, but any disruption results in serious health problems.