Cellular Respiration and Fermentation Processes
Cellular Respiration
Cellular respiration is the process where glucose is completely oxidized to CO2 and H2O with O2 intervention. This catabolic pathway occurs in the mitochondria of eukaryotes or in the cytoplasm and plasma membrane of prokaryotes.
The pyruvate obtained in glycolysis is broken down in three stages:
1. Oxidative Decarboxylation of Pyruvate
Pyruvate from glycolysis enters the mitochondrial matrix and undergoes decarboxylation, releasing a CO2 molecule, while NAD+ is reduced to NADH. An acetyl group (CH3-CO) is formed and activated, producing acetylCoA. Since glycolysis produces two pyruvate molecules per glucose molecule, this phase results in 2 acetylCoA, 2 NADH, and 2 CO2 + 2 H+.
2. Krebs Cycle
The Krebs cycle is a metabolic pathway located in the mitochondrial matrix where acetylCoA is completely oxidized to CO2 and H+. The equation is: AcetylCoA + ADP + Pi + 3 NAD+ + FAD → 2 CO2 + CoA-SH + ATP + 3 NADH + 3 H+ + FADH2. The ATP corresponds to the transformation of GTP found in the cycle.
Krebs Cycle Balance
The Krebs cycle produces little energy in the form of ATP (only 2 ATP molecules). Most energy is stored in the electrons and H+ from the reduced coenzymes (NADH and FADH2), which travel through the respiratory chain to O2, generating most of the energy in cellular respiration. The carbon skeleton of glucose, entering as acetyl groups, is completely degraded to CO2, and coenzyme A is recovered.
3. Electron Transport and Oxidative Phosphorylation
High-energy electrons from NADH + H+ and FADH2 are transported through the electron transport chain to O2, which is reduced to H2O. The electron transport chain consists of four protein and coenzyme complexes. Electrons flow through redox reactions from higher to lower energy levels, ultimately reaching O2.
According to the chemiosmotic hypothesis, the energy released by electrons moving from NADH or FADH2 to O2 is used to translocate H+ from the matrix to the intermembrane space, generating an electrochemical gradient across the inner mitochondrial membrane.
The electrochemical gradient drives H+ back into the matrix through ATP synthase. The energy released by H+ flow is used to phosphorylate ADP, generating ATP.
Cellular Respiration Balance
To determine the ATP yield of cellular respiration, consider substrate-level phosphorylation in glycolysis and the Krebs cycle, and oxidative phosphorylation from NADH and FADH2.
ATP Synthesized by Substrate-Level Phosphorylation
- Glycolysis: 2 ATP (3 ATP if glucose is from glycogenolysis)
- Krebs Cycle: 2 ATP
ATP Obtained by Oxidative Phosphorylation
- From NADH in Glycolysis: 2 NADH from glycolysis must enter the mitochondrial matrix. The malate shuttle (heart, kidney, liver) yields 3 ATP per NADH. The glycerol phosphate shuttle (skeletal muscle, brain) yields 2 ATP per NADH.
- From NADH in Pyruvate Decarboxylation: 6 ATP (2 NADH per glucose molecule).
- From NADH and FADH2 in the Krebs Cycle: 22 ATP per glucose molecule (2 cycles). Each acetylCoA yields 11 ATP: 3 NADH (9 ATP) and 1 FADH2 (2 ATP).
Fermentation
Fermentation is a metabolic process in the hyaloplasm that produces energy anaerobically through partial oxidation of glucose and other organic fuels. Substrates are usually carbohydrates, but some bacteria ferment proteins and amino acids.
Fermentation Features
- The final electron acceptor is an organic molecule, not O2.
- Glucose degradation is incomplete, and the final product is another organic molecule, retaining most of glucose’s energy.
- Energy yield is 2 ATP per glucose molecule from glycolysis. NADH is consumed to reduce pyruvate or acetaldehyde, regenerating NAD+ for glycolysis.
Lactic Acid Fermentation
Pyruvic acid is reduced to lactic acid under anaerobic conditions. Pyruvic acid accepts electrons from NADH + H+ produced in glycolysis, catalyzed by lactate dehydrogenase. Equation: Glucose + 2 ADP + 2 Pi → 2 ATP + 2 Lactic acid.
Lactic acid fermentation occurs in microorganisms like Lactobacillus and Streptococcus, used in cheese and yogurt production. It also occurs in skeletal muscle during intense exercise when O2 supply is insufficient. Lactic acid accumulation causes muscle soreness and is later converted back to glucose through gluconeogenesis.
Alcoholic Fermentation
Pyruvate is converted to ethanol under anaerobic conditions. Pyruvate loses a CO2 molecule and is transformed into acetaldehyde, which is then reduced to ethanol by NADH + H+ from glycolysis. Equation: Glucose + 2 ADP + 2 Pi → Ethanol + 2 CO2 + 2 ATP.
Alcoholic fermentation is performed by Saccharomyces yeasts, used in beer and wine production. It is also used in bread making, where CO2 and alcohol are eliminated during baking.
Amphipathic Status of the Krebs Cycle
The Krebs cycle has dual roles in cell metabolism:
- Catabolic Functions: AcetylCoA oxidized in the Krebs cycle comes from glucose, fatty acid oxidation, or amino acid degradation. The Krebs cycle is where carbohydrate, lipid, and amino acid catabolism converge.
- Anabolic Functions: The Krebs cycle provides precursors for biosynthetic pathways. Oxaloacetate can synthesize amino acids and glucose. Citrate can synthesize fatty acids and sterols. α-Ketoglutarate can synthesize purines and nonessential amino acids like glutamic acid, glutamine, or proline. SuccinylCoA can synthesize heme.
Other Catabolic Pathways
Fatty Acid Oxidation
Fatty acid oxidation occurs in the mitochondrial matrix via the β-oxidation pathway (Lynen helix). Fatty acids are degraded by sequential removal of two-carbon fragments as acetylCoA.
Fatty acids enter the mitochondria and are activated by coenzyme A, forming acylCoA. AcylCoA undergoes β-oxidation, producing acetylCoA, FADH2, and NADH + H+. The process repeats until the fatty acid is fully oxidized. AcetylCoA enters the Krebs cycle, and FADH2 and NADH + H+ are regenerated in the respiratory chain.
Amino Acid Degradation
Free amino acids from protein degradation are degraded based on their structure, converging on the Krebs cycle.
