Glycolysis and Cellular Respiration Study Notes
Introduction to Glycolysis
Glycolysis, derived from the Greek words "glykys" (sweet) and "lysis" (splitting), is the foundational metabolic pathway that breaks down a six-carbon glucose molecule into two three-carbon pyruvate molecules.
It occurs in the cytoplasm of virtually all living cells and is crucial for aerobic and anaerobic respiration.
This multi-stage process converts the chemical energy of glucose into ATP and NADH, representing the initial energy extraction from fuel molecules.
Energy Dynamics in Glycolysis
To understand the energy transformations, consider a hypothetical energy level diagram (like a graph) for glycolysis:
Points labeled A, B, C, D could represent various energy states of intermediates.
Point A would generally represent the high energy state of an intact glucose molecule at the start.
Point B often signifies the initial energy investment where ATP is consumed to phosphorylate glucose, slightly increasing its instability.
Point C might illustrate the cleavage of the six-carbon molecule into two three-carbon molecules, each still rich in potential energy.
Point D typically indicates the end of the energy liberation phase, demonstrating a net energy gain, but also highlighting that a substantial amount of chemical energy still resides within the pyruvate molecules.
Key takeaway: While glycolysis generates a net gain of ATP, pyruvate still holds a significant amount of chemical energy, much of which is subsequently harvested in the later stages of cellular respiration.
Products of Glycolysis
End Products for each glucose molecule:
Formation of two molecules of pyruvate (CH3COCOO^-(+H^+)) from one glucose molecule (C6H{12}O6).
Data on ATP and NADH involved:
Investment Phase (Energy-Requiring Phase):
Two ATP molecules are consumed to phosphorylate glucose and its derivatives, making them more reactive and facilitating their breakdown. This phase effectively uses energy to destabilize the glucose molecule.
Energy Liberation Phase (Energy-Releasing Phase):
Four ATP molecules are produced via substrate-level phosphorylation, resulting in a net gain of 2 ATP per glucose molecule (4 ext{ ATP produced} - 2 ext{ ATP consumed} = 2 ext{ net ATP}).
Additionally, two NADH molecules are produced. These electron carriers are formed through the oxidation of two molecules of G3P (Glyceraldehyde 3-phosphate), carrying high-energy electrons to be used in later stages of cellular respiration.
Phases of Glycolysis
Energy Investment Phase:
This phase begins with glucose and consumes two ATP molecules per glucose.
Step 1: Glucose is phosphorylated by hexokinase, using 1 ATP, to form Glucose-6-phosphate.
Step 2: Glucose-6-phosphate is isomerized to Fructose-6-phosphate.
Step 3: Fructose-6-phosphate is phosphorylated by phosphofructokinase, using a second ATP, to form Fructose-1,6-bisphosphate. This is a key regulatory step.
These steps involve endergonic reactions where energy from ATP hydrolysis is used to attach phosphate groups, priming the glucose molecule for cleavage.
Cleavage Phase:
Fructose-1,6-bisphosphate is cleaved by the enzyme aldolase into two three-carbon isomers:
Dihydroxyacetone phosphate (DHAP)
Glyceraldehyde 3-phosphate (G3P)
DHAP is then rapidly converted to G3P by an isomerase, ensuring that both three-carbon molecules can proceed through the subsequent energy liberation phase.
Energy Liberation Phase:
This phase generates ATP and NADH.
Each of the two G3P molecules goes through a series of reactions:
Oxidation and Phosphorylation: G3P is oxidized and phosphorylated to 1,3-bisphosphoglycerate, producing 1 NADH molecule per G3P (2 NADH total) through the enzyme glyceraldehyde-3-phosphate dehydrogenase.
Substrate-Level Phosphorylation 1: A phosphate group is transferred from 1,3-bisphosphoglycerate to ADP, forming ATP (2 ATP total) catalyzed by phosphoglycerate kinase, resulting in 3-phosphoglycerate.
Further rearrangements lead to phosphoenolpyruvate (PEP).
Substrate-Level Phosphorylation 2: A phosphate group is transferred from PEP to ADP, forming ATP (2 ATP total) catalyzed by pyruvate kinase, resulting in pyruvate.
This phase clearly indicates that glucose is not fully broken down yet; the pyruvate molecules still contain much chemical energy that can be further extracted.
Interaction with Other Topics
Relation to redox reactions:
During glycolysis, glucose is partially oxidized (loses electrons and hydrogens) while the electron carrier NAD+ is reduced by accepting these electrons and hydrogens to form NADH. This NAD^+/NADH couple is central to energy transfer.
Activation energy: All metabolic reactions, including those in glycolysis, require an initial input of energy to reach their transition state, known as activation energy. Enzymes like hexokinase and phosphofructokinase lower this activation energy, allowing the reactions to proceed at physiological temperatures, demonstrating the close relationship between energy dynamics and thermodynamics in metabolic processes.
Case Study Reminder
A case study on cellular respiration is due, with a specific focus on testing various metabolic toxins.
The study requires clarity on writing indicators and a deep understanding of the impact of these toxins on specific metabolic processes, such as glycolysis, the Krebs cycle, or oxidative phosphorylation.
Continuing the Discussion on Cellular Respiration
Overview of Stages of Cellular Respiration
Cellular respiration is a comprehensive catabolic pathway that fully breaks down glucose in the presence of oxygen to produce a large amount of ATP. It consists of four main stages:
Glycolysis: The breakdown of glucose into pyruvate in the cytoplasm.
Pyruvate Oxidation: The conversion of pyruvate into acetyl CoA, occurring in the mitochondrial matrix.
Citric Acid Cycle (Krebs Cycle): A series of reactions that further oxidize acetyl CoA, occurring in the mitochondrial matrix.
Oxidative Phosphorylation: The primary mechanism of ATP synthesis, involving the electron transport chain and chemiosmosis, occurring on the inner mitochondrial membrane.
Pyruvate Oxidation
This crucial transitional step connects glycolysis to the citric acid cycle. It occurs in the mitochondrial matrix (in eukaryotes). The pyruvate dehydrogenase complex catalyzes three reactions:
Decarboxylation: The carboxyl group of pyruvate is removed and released as a molecule of CO_2. Each pyruvate loses one carbon atom.
Oxidation: The remaining two-carbon molecule is oxidized, and the electrons are transferred to NAD^+ to form NADH.
Coenzyme A Attachment: The oxidized two-carbon acetate group is attached to coenzyme A, forming acetyl CoA. This molecule is now ready to enter the citric acid cycle.
Citric Acid Cycle (Krebs Cycle)
This cycle completely breaks down the carbon atoms originally from glucose, occurring in the mitochondrial matrix. It processes two acetyl CoA molecules per glucose:
Input: Each of the two acetyl CoA molecules (from pyruvate oxidation) enters the cycle by combining with a four-carbon compound, oxaloacetate, to form a six-carbon citrate molecule.
Carbon Release: Through a series of oxidation steps, two carbon atoms from each acetyl CoA are released as CO2 (for a total of four CO2 molecules per glucose molecule, combining with the two from pyruvate oxidation, making all six carbons of glucose released as CO_2 by the end of this cycle).
Production of Electron Carriers and ATP (per one acetyl CoA turn):
Three NADH molecules are produced.
One FADH2 molecule is produced.
One ATP (or GTP, which is readily converted to ATP) is generated via substrate-level phosphorylation.
Since two acetyl CoA molecules enter per glucose, these yields are doubled: 6 NADH, 2 FADH2, and 2 ATP per glucose molecule.
Summary of Citric Acid Cycle Dynamics
The cycle regenerates oxaloacetate, which is essential to combine with incoming acetyl CoA, making it a continuous cycle rather than a linear pathway.
The main objective is the complete oxidation of carbon backbones from acetyl CoA, extracting high-energy electrons (carried by NADH and FADH2) for the final stage of ATP production.
Other Energy Sources
Cells are adaptable and can utilize alternative energy sources (fats and proteins) to feed into the cellular respiration pathways:
Fats: Triglycerides are hydrolyzed into glycerol and fatty acids.
Glycerol can be converted into glyceraldehyde-3-phosphate (G3P) and enter glycolysis.
Fatty acids undergo beta-oxidation, a process that breaks them down into two-carbon units, which are then converted into acetyl CoA and enter the citric acid cycle. Fats are a highly efficient energy storage.
Proteins: Proteins are degraded into their constituent amino acids.
The amino groups (NH_2) are removed (deamination).
The remaining carbon skeletons of the amino acids can enter cellular respiration at various points: some are converted to pyruvate, others to acetyl CoA, and still others directly into intermediates of the citric acid cycle (e.g., alpha-ketoglutarate, succinyl CoA, fumarate, oxaloacetate).
Oxidative Phosphorylation
This is the final and most productive stage of ATP synthesis, utilizing the potential energy stored in NADH and FADH2.
Electron Transport Chain (ETC):
Located on the inner mitochondrial membrane (cristae), the ETC consists of four major protein complexes (Complex I, II, III, IV), along with two mobile carriers (ubiquinone/Q and cytochrome c).
High-energy electrons from NADH (entering at Complex I) and FADH2 (entering at Complex II) are passed down a series of redox reactions through these complexes.
As electrons drop in energy level at each transfer, the released energy is used by Complexes I, III, and IV to pump protons (H^+ ions) from the mitochondrial matrix into the intermembrane space, establishing a steep electrochemical gradient, known as the proton motive force.
The final electron acceptor at the end of the chain is oxygen, which combines with electrons and protons to form water (H_2O).
ATP Synthase Activity (Chemiosmosis):
The proton motive force drives the synthesis of ATP.
H+ ions, concentrated in the intermembrane space, flow back down their electrochemical gradient into the mitochondrial matrix through a specialized protein complex called ATP synthase.
This flow of protons provides the kinetic energy that causes the rotor and catalytic knob of ATP synthase to turn, inducing conformational changes that catalyze the phosphorylation of ADP to ATP (ADP + P_i
ightarrow ATP).This process, where energy stored in a hydrogen ion gradient is used to drive ATP synthesis, is known as chemiosmosis.
ATP Yield from Cellular Respiration
The theoretical maximum ATP yield from the complete oxidation of one glucose molecule is approximately 30-34 ATP in eukaryotes. This number can vary depending on the efficiency of the shuttle system used to transport cytoplasmic NADH into the mitochondria.
The contributions from different electron carriers are:
Roughly 2.5 ATP are produced for each NADH molecule that donates its electrons to the ETC.
Approximately 1.5 ATP are produced for each FADH2 molecule.
Considering: 2 net ATP from glycolysis, 2 NADH from glycolysis, 2 NADH from pyruvate oxidation, 6 NADH from Citric Acid Cycle, and 2 FADH2 from Citric Acid Cycle, we get a total theoretical yield.
Comparison Between Eukaryotes and Prokaryotes
In prokaryotic cells, the absence of membrane-bound organelles like mitochondria significantly affects the ATP yield and location of processes:
All stages of cellular respiration occur in the cytoplasm or on the prokaryotic cell membrane (which serves a similar function to the inner mitochondrial membrane for the ETC).
The overall yield of ATP from cellular respiration is typically lower (e.g., 32-34 ATP for prokaryotes vs. 30-32 for eukaryotes via different shuttle systems) compared to theoretical eukaryotic yields because specific energy-costly transport systems (like those for NADH from glycolysis into mitochondria) are not needed. However, the exact efficiency can vary.
Conclusion and Important Points to Remember
A detailed understanding of each step of cellular respiration and its regulation is essential for comprehending cellular energy production.
Recognize that glycolysis is merely the initial step; the subsequent stages (pyruvate oxidation, citric acid cycle, and oxidative phosphorylation) are critical for the complete breakdown of glucose and to maximize ATP extraction.
Remember the intricate interconnections between different metabolic pathways and their remarkable flexibility in terms of utilizing various energy sources (carbohydrates, fats, proteins) to meet the body's dynamic needs for cellular metabolism. This adaptability underscores the complexity and efficiency of biological energy systems.