The hidden logic behind life's pathways | EoB Ch00

Henrik Kacser developed metabolic control analysis in the 1970s, providing mathematical frameworks for understanding pathway optimization. Systems biologists use flux balance analysis to predict optimal metabolic configurations. Metabolic engineers redesign pathways for biotechnology applications maximizing yield and minimizing enzyme investment.

Fritz Lipmann and Herman Kalckar discovered ATP’s role as energy currency in the 1940s, with Lipmann receiving the 1953 Nobel Prize. Biochemists quantify ATP production and consumption across metabolic pathways. Cell biologists measure ATP levels to assess cellular health and metabolic state.

Gustav Embden and Otto Meyerhof elucidated glycolysis in the 1920s-1930s, earning Meyerhof the 1922 Nobel Prize. Biochemists study glycolysis as the central pathway converting glucose to pyruvate. Cell biologists examine how cells regulate glycolysis to meet energy demands during different metabolic states.

Charles Darwin’s natural selection theory explains how metabolic efficiency differences drive evolutionary outcomes. Evolutionary biochemists study how selection optimizes enzyme catalysis and pathway design. Microbiologists observe real-time metabolic evolution in laboratory populations under nutrient limitation.

Emil Fischer proposed the lock-and-key model of enzyme specificity in 1894. James Sumner first crystallized an enzyme (urease) in 1926, proving enzymes are proteins. Biochemists study enzyme mechanisms, kinetics, and regulation. Biotechnologists engineer enzymes for industrial applications from laundry detergents to pharmaceutical synthesis.

W. John Albery and Jeremy Knowles characterized diffusion-limited enzymes in the 1970s. Biochemists recognize triose phosphate isomerase—the enzyme interconverting glycolysis’s three-carbon intermediates—as approaching catalytic perfection. Enzymologists study how evolution optimizes catalytic efficiency against physical constraints.

Biochemists studying aldolase enzyme mechanism discovered why fructose-1,6-bisphosphate splits symmetrically into two three-carbon molecules. Metabolic engineers recognize this symmetry as critical for glycolytic efficiency. Structural biologists examine the chemical motif enabling favorable cleavage at the central carbon-carbon bond.