Cellular Metabolism Pathways

Why This Matters

Cellular metabolism isn't just a collection of chemical reactions to memorize—it's the fundamental engine that powers every living cell. On the AP exam, you're being tested on your understanding of how cells harvest energy from nutrients, store it in usable forms, and channel it toward building the molecules life requires. These pathways connect directly to major course themes: energy transfer, enzyme regulation, compartmentalization, and the integration of catabolic and anabolic processes.

The key to mastering this topic is recognizing that metabolism is a coordinated network, not isolated reactions. Glycolysis feeds the citric acid cycle, which feeds oxidative phosphorylation. The pentose phosphate pathway supplies NADPH for biosynthesis. Gluconeogenesis reverses glycolysis when glucose runs low. Don't just memorize ATP yields and enzyme names—know why each pathway exists, where it occurs, and how it connects to the bigger metabolic picture. That conceptual understanding is what separates a 3 from a 5.

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Energy-Harvesting Pathways (Catabolism)

These pathways break down nutrients to capture energy in ATP and electron carriers. The central strategy is stepwise oxidation—removing electrons from fuel molecules and using them to drive ATP synthesis.

Glycolysis

• Converts glucose to pyruvate—this 10-step pathway yields a net gain of 2 ATP and 2 NADH per glucose molecule
• Occurs in the cytoplasm and requires no oxygen, making it the universal starting point for glucose metabolism in both aerobic and anaerobic organisms
• Regulated at three key enzymes—hexokinase, phosphofructokinase (PFK), and pyruvate kinase control flux through the pathway based on cellular energy status

Citric Acid Cycle (Krebs Cycle)

• Completes the oxidation of acetyl-CoA—each turn produces 3 NADH, 1 FADH₂, and 1 GTP, feeding electrons to the transport chain
• Located in the mitochondrial matrix—this compartmentalization keeps the cycle's intermediates concentrated and separate from cytoplasmic reactions
• Integrates multiple fuel sources—acetyl-CoA enters from carbohydrates, fats, and proteins, making this cycle the metabolic hub of the cell

Oxidative Phosphorylation

• Generates the majority of cellular ATP—approximately 30-32 ATP per glucose through chemiosmosis at the inner mitochondrial membrane
• Electron transport creates a proton gradient—NADH and FADH₂ donate electrons to protein complexes that pump $H^+$ into the intermembrane space
• Oxygen is the final electron acceptor—without $O_2$ to accept electrons, the chain backs up and ATP synthesis halts, which is why cyanide poisoning is lethal

Fatty Acid Oxidation (Beta-Oxidation)

• Breaks fatty acids into 2-carbon acetyl-CoA units—each cycle releases 1 NADH and 1 FADH₂, making fats extremely energy-dense
• Occurs in the mitochondrial matrix—fatty acids must be transported across the membrane via the carnitine shuttle before oxidation begins
• Regulated by energy availability—when ATP is abundant, beta-oxidation slows; during fasting or exercise, it accelerates to meet energy demands

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Biosynthetic Pathways (Anabolism)

These pathways build complex molecules from simpler precursors. They typically require energy input (ATP) and reducing power (NADPH) to drive thermodynamically unfavorable reactions.

Pentose Phosphate Pathway

• Generates NADPH for biosynthesis—the oxidative phase produces 2 NADPH per glucose-6-phosphate, essential for fatty acid synthesis and antioxidant defense
• Produces ribose-5-phosphate—this 5-carbon sugar is the backbone of nucleotides, making this pathway critical for DNA and RNA synthesis
• Operates in the cytoplasm—runs parallel to glycolysis, with intermediates that can shuttle between pathways depending on cellular needs

Fatty Acid Synthesis

• Builds fatty acids from acetyl-CoA—the enzyme fatty acid synthase adds 2-carbon units in a repeating cycle until a 16-carbon chain (palmitate) is complete
• Requires NADPH as the reducing agent—this is why the pentose phosphate pathway and fatty acid synthesis are metabolically linked
• Regulated by insulin—fed-state hormonal signals activate synthesis, while fasting and glucagon inhibit it, coordinating fat storage with nutritional status

Gluconeogenesis

• Synthesizes glucose from non-carbohydrate precursors—lactate, glycerol, and certain amino acids can all be converted to glucose via this pathway
• Bypasses three irreversible glycolytic steps—enzymes like pyruvate carboxylase and PEPCK catalyze the energetically unfavorable reverse reactions
• Primarily occurs in the liver—this organ maintains blood glucose during fasting, ensuring the brain and red blood cells have constant fuel supply

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Nitrogen-Handling Pathways

These pathways manage the nitrogen atoms found in amino acids and nucleotides. Unlike carbon, which can be exhaled as $CO_2$, nitrogen must be carefully processed and excreted to avoid toxicity.

Amino Acid Metabolism

• Transamination transfers amino groups—enzymes called aminotransferases shuffle nitrogen between molecules, allowing interconversion of amino acids
• Deamination removes nitrogen as ammonia—this toxic compound must be quickly processed, especially during protein breakdown or amino acid catabolism
• Carbon skeletons enter central metabolism—after nitrogen removal, the remaining carbons feed into glycolysis, the citric acid cycle, or gluconeogenesis

Urea Cycle

• Converts toxic ammonia to urea—this water-soluble, non-toxic compound can be safely excreted by the kidneys
• Operates exclusively in the liver—the cycle spans both mitochondria (first two steps) and cytoplasm (remaining steps), requiring compartmentalized coordination
• Links to the citric acid cycle—fumarate produced by the urea cycle enters the citric acid cycle, connecting nitrogen disposal to energy metabolism

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Photosynthetic Energy Capture

This pathway is unique to plants, algae, and cyanobacteria—it captures light energy and converts it to chemical energy. Photosynthesis is the ultimate source of nearly all biological energy on Earth.

Photosynthesis (Light and Dark Reactions)

• Light reactions capture solar energy—chlorophyll in the thylakoid membranes absorbs photons, driving electron flow that produces ATP and NADPH
• The Calvin cycle fixes carbon—in the stroma, the enzyme RuBisCO attaches $CO_2$ to a 5-carbon sugar, ultimately producing G3P for glucose synthesis
• Oxygen is a byproduct of water splitting—the light reactions split $H_2O$ to replace electrons lost by chlorophyll, releasing $O_2$ into the atmosphere

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Quick Reference Table

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Self-Check Questions

1. Which two pathways both produce NADPH, and why is this molecule important for biosynthesis rather than energy production?

2. Compare the locations and functions of beta-oxidation and fatty acid synthesis. Why does the cell keep these pathways in separate compartments?

3. If a cell is starving and blood glucose is low, which pathway becomes active in the liver—glycolysis or gluconeogenesis? What precursors might fuel this pathway?

4. An FRQ asks you to trace the flow of electrons from glucose to water in aerobic respiration. Which three major pathways would you discuss, and what electron carriers connect them?

5. Compare and contrast oxidative phosphorylation in mitochondria with the light reactions in chloroplasts. What structural and functional features do they share, and how do their energy sources differ?