Questions and Answers
Which substrate is primarily used in the TCA cycle?
What is the primary regulatory site in glycolysis?
Which molecule is produced as a result of the bisphosphoglycerate shunt?
Which of the following pathways is activated when ATP needs are low?
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How is ATP homeostasis primarily maintained in cells?
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Which of the following is a source of acetyl-CoA for the TCA cycle?
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What role does 2,3-BPG play in red blood cells?
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What is the primary function of the enzyme pyruvate dehydrogenase in cellular metabolism?
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What is the primary function of anaerobic glycolysis in tissues with limited oxygen supply?
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Which of the following is a net reaction of anaerobic glycolysis?
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What is a consequence of excess lactate in the body?
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Which tissues primarily rely on anaerobic glycolysis due to their low oxygen supply?
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Which enzyme is responsible for converting pyruvate to lactate in anaerobic glycolysis?
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What intermediates are generated from glycolysis that can serve as precursors for nucleotide synthesis?
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How does the liver utilize lactate produced during anaerobic glycolysis?
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Which of the following is NOT a role of glycolysis in the cell?
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What reaction is catalyzed by glyceraldehyde-3-phosphate dehydrogenase in glycolysis?
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Which enzyme is responsible for the final transfer of phosphate to ADP, producing ATP and pyruvate?
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What is produced during the oxidation of 1,3-bisphosphoglycerate in glycolysis?
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In anaerobic metabolism, what does lactate dehydrogenase convert pyruvate into?
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Why is NADH reoxidized during glycolysis?
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What is the primary fate of pyruvate in the presence of oxygen?
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Which compound is generated from the conversion of 3-phosphoglycerate in glycolysis?
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What distinguishes aerobic glycolysis from anaerobic glycolysis?
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Study Notes
Glycolysis Overview
- Aldolase catalyzes aldol cleavage, forming a covalent bond with the substrate using a lysine residue.
- Each glucose molecule yields two glyceraldehyde-3-phosphate (G3P) for glycolysis.
Glyceraldehyde-3-Phosphate Oxidation
- Glyceraldehyde-3-phosphate dehydrogenase converts G3P to 1,3-bisphosphoglycerate (1,3-BPG).
- NAD+ is reduced to NADH during this process, involving a high-energy thioester intermediate.
- The reaction creates a high-energy acyl phosphate bond, initiating substrate-level phosphorylation.
ATP Formation
- 1,3-BPG donates a phosphate to ADP through 3-phosphoglycerate kinase, generating ATP and 3-phosphoglycerate.
- The acyl phosphate bond's energy drives ATP synthesis.
Conversion to Phosphoenolpyruvate (PEP)
- 3-phosphoglycerate is converted to 2-phosphoglycerate, followed by dehydration to form PEP, which possesses a high-energy enol phosphate bond.
Final ATP Generation
- PEP transfers its phosphate to ADP via pyruvate kinase, producing ATP and pyruvate.
- This reaction is energetically favorable and irreversible.
Oxidative Fates of Pyruvate and NADH
- NADH must be reoxidized to NAD+ for glycolysis to continue, achieved via two pathways: aerobic and anaerobic.
Aerobic Pathway
- Electrons are transferred to the mitochondrial electron transport chain (ETC) using shuttles and oxygen, oxidizing pyruvate to acetyl CoA for the TCA cycle.
Anaerobic Pathway
- NADH is reoxidized to NAD+ by converting pyruvate to lactate through lactate dehydrogenase (LDH), diverting pyruvate from the TCA cycle.
ATP Generation Comparison
- Aerobic glycolysis produces more ATP than anaerobic glycolysis, with shuttle systems facilitating NADH oxidation.
Mitochondrial Membrane Characteristics
- The inner mitochondrial membrane's impermeability to NADH necessitates shuttles to transfer electrons to the ETC.
Anaerobic Glycolysis Overview
- Occurs under limited oxidative capacity (e.g., in red blood cells).
- Results in the net reaction: Glucose + 2 ADP + 2 Pi → 2 lactate + 2 ATP + 2 H2O + 2 H⁺.
Acid Production
- Glycolysis results in pyruvic acid, which is reduced to lactic acid, dissociating into lactate and H⁺.
- High lactate levels can lower blood pH, leading to lactic acidosis.
Tissues Relying on Anaerobic Glycolysis
- Red and white blood cells, kidney medulla, eye tissues, and skeletal muscles utilize anaerobic glycolysis due to high glycolytic enzyme levels and low ATP demands.
Role of Anaerobic Glycolysis
- Provides ATP when oxygen is scarce; eye cells rely on it to prevent opacities in structures.
Fate of Lactate
- Lactate can be converted back to pyruvate in the liver, heart, and muscle; in the liver, it can contribute to gluconeogenesis (Cori cycle).
LDH Isoenzymes
- LDH consists of A (muscle) and B (heart) subunits, forming various tetramers (M4, M3H1, M2H2, M1H3, H4) that play roles in lactate and pyruvate conversions.
Other Functions of Glycolysis
- Generates precursors for nucleotide synthesis, produces various sugars, and synthesizes amino acids like serine and alanine.
Liver Functions
- Major biosynthetic site, converting pyruvate into fatty acids and synthesizing glucose from lactate, glycerol, and amino acids (gluconeogenesis).
Bisphosphoglycerate Shunt
- Converts 1,3-BPG to 2,3-BPG in red blood cells, which inhibits oxygen binding to heme and reenters glycolysis as 3-phosphoglycerate.
Regulation of Glycolysis by ATP Needs
- Regulation occurs at the rate-limiting steps, mainly via PFK-1 and pyruvate dehydrogenase, ensuring proper product flow into alternative pathways.
Major Regulatory Sites
- PFK-1 serves as a primary control point in glycolysis, while pyruvate dehydrogenase links glycolysis to the TCA cycle.
Regulation Mechanisms
- ATP homeostasis is maintained by adjusting glycolytic activity based on cellular ATP requirements.
Tissue-Specific Isoenzymes
- Isoenzymes allow glycolysis regulation to adapt to tissue-specific conditions; liver pyruvate kinase isoenzyme inhibits glycolysis during active gluconeogenesis.
TCA Cycle Overview
- Produces over two-thirds of ATP from oxidized fuel sources using acetyl CoA derived from fatty acids, glucose, amino acids, acetate, and ketone bodies.
- Oxidation generates CO₂ and conserves energy as NADH, FAD(2H), and GTP, with NADH and FAD(2H) donating electrons to the ETC for ATP production via oxidative phosphorylation.
- Also known as the Krebs cycle, named after Sir Hans Krebs.
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Description
This quiz explores key processes in glycolysis, focusing on the roles of aldolase and glyceraldehyde-3-phosphate dehydrogenase. You will learn how these enzymes facilitate substrate-level phosphorylation and oxidation of G3P to 1,3-bisphosphoglycerate, contributing to energy production in cells.
