An Overview of Metabolism and Biochemical Energy

Core Concepts

Catabolism and anabolism are complementary halves

Catabolic reactions are predominantly oxidative and exergonic: they release energy as ATP and reduced coenzymes. Anabolic reactions are predominantly reductive and endergonic: they consume ATP and NADPH. A key organic-chemistry consequence: a degradative pathway is usually not the exact reverse of its biosynthetic pathway. Fatty-acid degradation (β-oxidation) and fatty-acid synthesis use different intermediates, different coenzymes, and different cellular locations, so each direction can be regulated independently.

ATP is the cell's energy currency

ATP is adenosine (adenine attached to ribose) carrying a chain of three phosphate groups. Energy is released when the terminal phosphoanhydride linkage is hydrolyzed:

ATP + H₂O → ADP + P_i   ΔG^°′ ≈ -30.5 kJ/mol (-7.3 kcal/mol)

The large negative ΔG^°′ does not mean the P–O bond is strong; the products are simply far more stable than the reactant (resonance stabilization of free phosphate, relief of charge repulsion, better solvation). Some reactions cleave ATP to AMP + PPᵢ (pyrophosphate, later hydrolyzed to two phosphates), effectively spending two phosphate-transfer equivalents, as in fatty-acid activation.

Reduced coenzymes carry electrons

NAD⁺ accepts a hydride ion (two electrons plus a proton) to become NADH; FAD accepts two electrons and two protons to become FADH₂. Both feed the electron-transport chain at different points: NADH enters at Complex I (about 2.5 ATP), FADH₂ at Complex II (about 1.5 ATP) — modern estimates; older texts used 3 and 2. NADPH has identical chemistry but an anabolic role: the reducing agent for biosynthesis (fatty-acid synthesis consumes 14 NADPH per palmitate).

Coupled reactions drive unfavorable processes

An endergonic reaction (ΔG > 0) cannot run by itself, but it can when coupled to a strongly exergonic reaction such as ATP hydrolysis, because free-energy changes are additive:

ΔG_total = ΔG_unfavorable + ΔG_{ATP hydrolysis}

The enzyme binds both substrates and channels the energy of ATP hydrolysis directly into the synthetic step.

Catabolism proceeds in three stages

1. Stage 1 — Macromolecules to building blocks: polysaccharides to monosaccharides, triacylglycerols to glycerol + fatty acids, proteins to amino acids. Little energy captured.
2. Stage 2 — Building blocks to acetyl CoA: glycolysis converts glucose to pyruvate; pyruvate becomes acetyl CoA; β-oxidation converts fatty acids to acetyl CoA. Some ATP and reduced coenzymes captured.
3. Stage 3 — Acetyl CoA to CO₂ and water: the citric acid cycle and oxidative phosphorylation extract most of the ATP and regenerate NAD⁺ and FAD.

High-energy compounds beyond ATP

Several intermediates hydrolyze with a large negative ΔG: phosphoenolpyruvate (PEP), 1,3-bisphosphoglycerate, creatine phosphate, and thioesters such as acetyl CoA. They act as high-energy donors in substrate-level phosphorylation and in priming biosynthetic reactions.

Common Confusions