Biochemistry I - Glycolysis
- Biochemistry
- Texas A&M University
- 21 pages
- Shared March 2026
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Study Guide Biochemistry I – Glycolysis 1. Glycolysis: ATP and NADH Production Glycolysis is a central metabolic pathway that breaks down glucose to produce energy. The energy - yielding phase of glycolysis involves a series of reactions between 3 - carbon molecules that generate ATP and NADH , the cell’s key energy carriers. 1.1 Energy - Yielding Phase of Glycolysis The first molecule that directly produces energy in this phase is glyceraldehyde - 3 - phosphate (G3P) . This molecule reacts with: • ADP • Inorganic phosphate (P ᵢ ) • NAD ⁺ The reaction is catalyzed by the enzyme glyceraldehyde - 3 - phosphate dehydrogenase .
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Study Guide 1.2 Mechanism of the Glyceraldehyde - 3 - Phosphate Reaction This reaction occurs in several important steps: 1. A thiol group from the enzyme attacks the aldehyde carbon of glyceraldehyde - 3 - phosphate. 2. This forms a thiohemiacetal intermediate . 3. NAD ⁺ then accepts two electrons , becoming NADH . 4. The aldehyde group of the substrate is oxidized to the level of a carboxylic acid . 5. Inorganic phosphate replaces the thiol group, forming 1,3 - bisphosphoglycerate . This step is crucial because it links oxidation to energy capture . 1.3 ATP Formation by Substrate - Level Phosphorylation The next step transfers a phosphate group from 1,3 - bisphosphoglycerate to ADP, producing ATP. This reaction is catalyzed by phosphoglycerate kinase . At this point: • Two ATP molecules were used earlier in glycolysis • Two ATP molecules are now regenerated So, the energy balance returns to zero . 1.4 Rearrangement of the Carbon Skeleton Next, 3 - phosphoglycerate is converted into 2 - phosphoglycerate by the enzyme phosphoglycerate mutase . This rearrangement prepares the molecule for the next energy - releasing step.
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Study Guide 1.5 Formation of Phosphoenolpyruvate (PEP) The enzyme enolase removes: • A hydroxyl group from carbon 3 • A hydrogen from carbon 2 This dehydration reaction forms a double bond, producing phosphoenolpyruvate (PEP) . 1.6 Why PEP Has High Energy PEP is an enol , and enols are usually less stable than keto compounds . PEP cannot easily convert to its keto form because of the phosphate group. When the phosphate is released: • PEP converts to the keto form (pyruvate) • A large amount of free energy is released This energy is used to make ATP. 1.7 Formation of ATP and Pyruvate The enzyme pyruvate kinase transfers the phosphate from PEP to ADP, forming ATP and pyruvate .
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Study Guide This step: • Is highly favorable • Produces two ATP molecules per glucose • Brings glycolysis into a positive energy balance Overall Reaction of Glycolysis Overall equation of glycolysis: Glucose + 2 ADP + 2 P ᵢ + 2 NAD ⁺ → 2 Pyruvate + 2 ATP + 2 NADH + 2 H ⁺ + 2 H ₂ O 1.8 Regeneration of NAD ⁺ : An Essential Step For glycolysis to continue, NADH must be converted back to NAD ⁺ . This regeneration can occur in two ways: • Anaerobically (without oxygen) • Aerobically (with oxygen) 1.9 Anaerobic Regeneration: Lactate Formation In animal muscle cells, NAD ⁺ is regenerated by transferring electrons to pyruvate , forming lactate . This reaction is catalyzed by lactate dehydrogenase .
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Study Guide This reaction oxidizes NADH back to NAD ⁺ . This pathway is also used by lactic acid bacteria in yogurt production. 1.10 Anaerobic Regeneration: Ethanol Formation In yeast and some microorganisms, pyruvate is converted into ethanol in two steps: 1. Pyruvate decarboxylase removes CO ₂ , forming acetaldehyde 2. Alcohol dehydrogenase reduces acetaldehyde to ethanol using NADH When ethanol is produced, the reaction of glycolysis becomes:
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Study Guide 1.11 Biological and Practical Significance of Ethanol Formation • High sugar content in grapes leads to higher ethanol production • Ethanol concentrations above ~14% inhibit fermentation • This explains limits in natural wine production Alcohol dehydrogenase also works in the reverse direction in humans: • Found in liver and intestines • Converts ethanol back to acetaldehyde • Acetaldehyde contributes to alcohol toxicity • Differences in intestinal enzyme levels explain why people respond differently to alcohol 1.12 Pyruvate to Acetyl - CoA: Entry into the TCA Cycle Under aerobic conditions, pyruvate is oxidatively decarboxylated to form acetyl - CoA , which enters the TCA cycle . This step connects glycolysis to oxidative metabolism. 1.13 Why Aerobic Metabolism Produces More ATP Louis Pasteur observed that oxygen inhibits fermentation in yeast. This is because: • Oxygen allows complete oxidation of glucose carbons to CO ₂ • More free energy is released • More ATP is produced than in fermentation High ATP levels then inhibit key glycolytic enzymes , slowing glycolysis. Key Takeaway • Glycolysis produces ATP and NADH from glucose • Substrate - level phosphorylation generates ATP directly • NAD ⁺ must be regenerated for glycolysis to continue • Anaerobic pathways form lactate or ethanol • Aerobic metabolism yields more ATP through complete oxidation
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Study Guide 2. Glycolysis Regulation Cells carefully control glycolysis so that energy is produced when needed and conserved when energy is plentiful . This control is achieved by regulating specific steps in the pathway rather than every reaction. 2.1 General Principle of Metabolic Regulation A key rule in metabolism is that regulation usually occurs at the first committed step of a pathway. A committed step is one after which the molecule has only one possible fate . However, glycolysis is connected to many other pathways. Some glycolytic intermediates are used to make: • Lipids • Amino acids • Nucleotides Because of this, glycolysis is regulated at more than one step , allowing the cell to coordinate energy production with biosynthesis. 2.2 Why Multiple Control Points Are Needed For example: • Dihydroxyacetone phosphate (DHAP) can be used to make glycerol , which is needed for fat (triglyceride) synthesis. • In a well - fed state, animals store energy as fat. • Even when ATP demand is low, glucose must still be converted into triose phosphates. Therefore, glycolysis must sometimes continue partially , without fully breaking glucose down to CO ₂ .
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