Proteins, Enzymes, and the Lock-and-Key Model
Enzymes make nearly every biochemical reaction the MCAT tests possible, and the way scientists have described how they work has itself evolved over more than a century. German chemist Emil Fischer proposed the first influential model in 1894: an enzyme’s active site and its substrate fit together like a lock and key, each shaped precisely to match the other, explaining why enzymes are so selective about which molecules they act on. The lock-and-key model was elegant, but too rigid to explain everything scientists observed; in 1958, biochemist Daniel Koshland proposed the induced fit model instead, arguing that an enzyme’s active site is flexible, subtly changing shape as the substrate binds to achieve an even tighter, more catalytically effective fit — a refinement, not a replacement, of Fischer’s original insight, and the model still taught today.
Amino acids, the building blocks enzymes and every other protein are constructed from, were identified individually over more than a century before the full set of 20 standard amino acids used in human proteins was established; threonine, the last of the 20 to be discovered, wasn’t isolated until 1935. Each amino acid’s side chain — the variable portion of its structure — determines whether it is hydrophobic or hydrophilic, acidic or basic, properties that in turn dictate how a protein folds into its three-dimensional shape once it’s assembled. That folded shape is not incidental; a protein’s function depends entirely on its structure, which is why conditions that denature proteins — extreme heat, extreme pH — cause them to lose function even though every amino acid in the chain remains chemically unchanged.
Glycolysis, the Krebs Cycle, and How Cells Make Energy
The metabolic pathways the MCAT tests in greatest depth — glycolysis, the citric acid cycle, and oxidative phosphorylation — were mapped out across the first half of the twentieth century by researchers working with surprisingly modest equipment for such foundational discoveries. German-British biochemist Hans Krebs described the citric acid cycle (the pathway that now carries his name) in 1937, working out the sequence of reactions by which a cell breaks down acetyl-CoA to generate the electron carriers that power ATP production, using little more than minced pigeon breast muscle tissue and careful measurement of oxygen consumption. Krebs received the 1953 Nobel Prize in Physiology or Medicine for the work, sharing it with biochemist Fritz Lipmann, whose separate discovery of coenzyme A explained the molecule that links glycolysis’s end products to the cycle Krebs had described.
Glycolysis itself — the ten-step breakdown of glucose into pyruvate that doesn’t require oxygen — was worked out even earlier, through the combined efforts of biochemists including Gustav Embden and Otto Meyerhof in the 1930s, which is why the pathway is sometimes called the Embden-Meyerhof pathway in older texts. Together, glycolysis, the citric acid cycle, and the electron transport chain that follows it represent one continuous energy-extraction system, and MCAT questions frequently test whether a given step occurs in the cytoplasm or the mitochondrial matrix, and whether it requires oxygen — distinctions that matter because they determine how a cell adapts when oxygen becomes scarce, shifting toward the far less efficient process of fermentation to keep glycolysis running.
Source: National Institutes of Health (NIH) and Encyclopaedia Britannica.