Aerobic respiration - Embden-Meyerhof pathway, Pentose phosphate pathway and Entner-Doudoroff pathway

Aerobic Respiration

Metabolism is divided into two: catabolism and anabolism. Catabolism is the breakdown of large, complex molecules into smaller, simpler ones, releasing energy that is either trapped for work or released as heat. Anabolism is the synthesis of complex molecules from simpler ones, a process that requires input of energy. The energy trapped during catabolism is used to carry out anabolic processes.

An amphibolic pathway is a metabolic pathway that serves both catabolic (breaking down) and anabolic (building up) functions. These pathways are crucial for metabolism because their intermediates can be either oxidized to release energy or used as building blocks for the synthesis of new cellular components. The glycolytic pathway and the citric acid cycle are examples of amphibolic pathways.

Catabolism can be classified based on the type of electron acceptor used to release energy. Fermentation is the process that occurs without an external electron acceptor, an endogenous molecule such as pyruvate or its derrivative acts as the electron acceptor.

Respiration utilizes an externally derived electron acceptor. Aerobic respiration uses oxygen as the final electron acceptor, while anaerobic respiration uses a different exogenous molecule, which is often an inorganic compound like nitrate, sulfate, or carbonate.

Aerobic respiration

Aerobic respiration is a process that occurs in the presence of oxygen. Cells break down glucose to produce energy in the form of molecules of adenosine triphosphate (ATP). This process is highly efficient and is the primary way most organisms, including humans, plants, and animals, generate energy.

The overall chemical equation for aerobic respiration is

 C_6​H₁₂​O₆ ​+ 6O₂ ​  →  6CO₂​+6H₂​O + Energy (ATP)

Aerobic respiration is a series of four interconnected stages.

Glycolysis: This stage does not require oxygen. During glycolysis, a single glucose molecule (a six-carbon sugar) is split into two molecules of pyruvate (a three-carbon compound). This process has a net yield of two ATP molecules and two NADH molecules, which are energy-carrying molecules.

Pyruvate Oxidation: The two pyruvate molecules from glycolysis are converted into acetyl-CoA (a two-carbon molecule). This step releases one molecule of carbon dioxide per pyruvate and produces one NADH molecule.

Krebs Cycle or Citric Acid Cycle: Acetyl-CoA enters the Krebs cycle. For each acetyl-CoA molecule, the cycle produces three NADH, one FADH₂, one ATP, and releases two molecules of carbon dioxide. Since each glucose molecule yields two acetyl-CoA molecules, the cycle runs twice per glucose molecule.

Oxidative Phosphorylation: This final stage takes place in the mitochondrial matrix in eukaryotes and plasma membrane in prokaryotes. The NADH and FADH₂ molecules produced in the previous stages donate their high-energy electrons to a series of protein complexes in the electron transport chain. As electrons move down the chain, their energy is used to pump protons across the membrane, creating a strong electrochemical gradient. This gradient drives the enzyme ATP synthase to create a large number of ATP molecules. At the end of the chain, oxygen acts as the final electron acceptor, combining with protons to form water.

 

 

Breakdown of Glucose to Pyruvate

Microorganisms break down sugars like glucose through various metabolic pathways. To simplify this, three primary routes are focused on for the catabolism of sugars into pyruvate and similar intermediates: glycolysis, the pentose phosphate pathway, and the Entner-Doudoroff pathway. These three pathways represent the main ways microorganisms degrade sugars.

The Glycolytic Pathway or Embden-Meyerhof pathway

Glycolysis is a ten-step catabolic pathway that breaks down one molecule of glucose into two molecules of pyruvate. It occurs in the cytoplasm of both prokaryotic and eukaryotic cells and can function with or without oxygen. The process is divided into two main stages: the energy investment phase and the energy payoff phase.

1. Energy Investment Phase (Six-Carbon Stage)

In this initial stage, the cell invests two ATP molecules to phosphorylate glucose and prime it for breakdown.

1. Phosphorylation of Glucose: An enzyme adds a phosphate group to glucose, forming glucose-6-phosphate. This step uses one molecule of ATP.
2. Isomerization: Glucose-6-phosphate is rearranged into its isomer, fructose-6-phosphate.
3. Second Phosphorylation: Another ATP is used to add a second phosphate group, converting fructose-6-phosphate into fructose-1,6-bisphosphate.
4. Cleavage: The six-carbon fructose-1,6-bisphosphate molecule is split into two three-carbon molecules: glyceraldehyde-3-phosphate and dihydroxyacetone phosphate.
5. Isomerization: The dihydroxyacetone phosphate molecule is immediately converted into glyceraldehyde-3-phosphate. At this point, one molecule of glucose has been converted into two molecules of glyceraldehyde-3-phosphate.

2. Energy Payoff Phase (Three-Carbon Stage)

This phase generates a net gain of ATP and NADH. Since two molecules of glyceraldehyde-3-phosphate are processed, all subsequent steps occur twice.

6. Oxidation and Phosphorylation: Each glyceraldehyde-3-phosphate molecule is oxidized, and a phosphate group is added, forming 1,3-bisphosphoglycerate. This step also reduces NAD+ to NADH.
7. First Substrate-Level Phosphorylation: The high-energy phosphate group on 1,3-bisphosphoglycerate is transferred to ADP, producing the first molecule of ATP and 3-phosphoglycerate. This is called substrate-level phosphorylation because a high-energy substrate directly donates a phosphate to ADP.
8. Phosphate Relocation: The phosphate group on 3-phosphoglycerate is moved to a different carbon, forming 2-phosphoglycerate.
9. Dehydration: A water molecule is removed from 2-phosphoglycerate, creating a high-energy molecule called phosphoenolpyruvate (PEP).
10. Second Substrate-Level Phosphorylation: The phosphate group from PEP is transferred to ADP, yielding the second molecule of ATP and the final product, pyruvate.

Summary of Net Yield

By the end of glycolysis, one glucose molecule has been converted into two pyruvate molecules.

• ATP: Four ATP molecules are produced (two per glyceraldehyde-3-phosphate), but two were used in the initial stage. This results in a net gain of 2 ATP.
• NADH: Two molecules of NADH are produced.
• Pyruvate: Two molecules of pyruvate are produced.

The overall equation for glycolysis is

Glucose + 2 ADP + 2 Pi​ + 2 NAD+ → 2 Pyruvate + 2 ATP + 2 NADH + 2 H+

 

(https://app.lecturio.com/)

 

The Pentose Phosphate Pathway

The pentose phosphate pathway (PPP), also known as the hexose monophosphate pathway is a metabolic pathway that can operate concurrently with glycolysis or the Entner-Doudoroff pathway. It is crucial for both biosynthesis (anabolic) and catabolism.

This a multi-step process that can be divided into two phases: the oxidative phase and the non-oxidative phase.

Oxidative Phase:

This irreversible phase focuses on the generation of NADPH and the synthesis of pentose sugars.

1. Glucose 6-phosphate is oxidized by glucose 6-phosphate dehydrogenase to form 6-phosphogluconate. In this step, NADP+ is reduced to NADPH.
2. 6-phosphogluconate is then oxidized and decarboxylated by 6-phosphogluconate dehydrogenase, producing ribulose 5-phosphate and releasing a molecule of CO₂​. This step also produces a second molecule of NADPH.

Non-Oxidative Phase:

This reversible phase involves the interconversion of various sugars to produce intermediates that can be channeled back into glycolysis.

• Ribulose 5-phosphate is isomerized to ribose 5-phosphate or epimerized to xylulose 5-phosphate.
• Transketolase and transaldolase, two key enzymes unique to this pathway, catalyze the transfer of carbon groups between sugars, creating a diverse pool of sugar phosphates.
• Transketolase transfers a two-carbon ketol group. For example, it transfers a two-carbon unit from xylulose 5-phosphate to ribose 5-phosphate, forming a seven-carbon sugar (sedoheptulose 7-phosphate) and a three-carbon sugar (glyceraldehyde 3-phosphate).
• Transaldolase transfers a three-carbon dihydroxyacetone group. For instance, it transfers a three-carbon unit from sedoheptulose 7-phosphate to glyceraldehyde 3-phosphate, producing fructose 6-phosphate and erythrose 4-phosphate.

The overall result is the conversion of three molecules of glucose 6-phosphate into two molecules of fructose 6-phosphate, one molecule of glyceraldehyde 3-phosphate, and three molecules of CO2​.

Anabolic and Catabolic functions of PPP

• The NADPH produced serves as a source of electrons for the reduction of molecules during biosynthesis.
• Sugar Synthesis: The pathway synthesizes four- and five-carbon sugars essential for various purposes.
• Erythrose 4-phosphate (a four-carbon sugar) is used to synthesize aromatic amino acids and vitamin B6​.
• Ribose 5-phosphate (a five-carbon sugar) is a key component of nucleic acids.
• Ribulose 1,5-bisphosphate is the primary CO₂​ acceptor in photosynthesis.
• The pathway can also supply carbon for hexose production (e.g., glucose for peptidoglycan synthesis) when an organism is growing on a pentose carbon source.
• ATP Production: The PPP can produce ATP. Glyceraldehyde 3-phosphate can enter the glycolytic pathway to be converted to ATP and pyruvate. The pyruvate can then be oxidized in the tricarboxylic acid (TCA) cycle for more energy. Some NADPH can be converted to NADH, which yields ATP when oxidized by the electron transport chain. The pathway can also catabolize pentoses and hexoses for energy.

(https://bio.libretexts.org/)

 

The Entner-Doudoroff (ED) pathway

The Entner-Doudoroff (ED) pathway is a metabolic route that serves as an alternative to glycolysis for the catabolism of glucose. It is particularly common in certain Gram-negative bacteria.

Steps

The ED pathway can be broken down into three main stages:

Initial Phosphorylation and Oxidation: The pathway begins with the same two steps as the pentose phosphate pathway. Glucose is first phosphorylated to glucose 6-phosphate, which is then oxidized to 6-phosphogluconate.  This oxidation step involves the reduction of NADP+ to NADPH.

Key Intermediate Formation: 6-phosphogluconate is dehydrated to form 2-keto-3-deoxy-6-phosphogluconate (KDPG). This molecule is the unique and central intermediate of the ED pathway.

Cleavage and Pyruvate Production: KDPG, is cleaved by the enzyme KDPG aldolase into two products, Pyruvate and Glyceraldehyde 3-phosphate.

The glyceraldehyde 3-phosphate then enters the second half of the glycolytic pathway to be converted into a second molecule of pyruvate. This latter conversion produces one molecule of ATP and one molecule of NADH.

(https://www.sciencefacts.net/)

Energy Yield

For each molecule of glucose metabolized through the ED pathway, the net energy and reducing power yield is:

• 1 ATP: Produced from the conversion of glyceraldehyde 3-phosphate to pyruvate.
• 1 NADPH: Produced during the oxidation of glucose 6-phosphate.
• 1 NADH: Produced during the conversion of glyceraldehyde 3-phosphate to pyruvate.

This yield is less than that of glycolysis (which produces 2 net ATP and 2 NADH per glucose). However, the NADPH produced is used for anabolic processes.

The ED pathway is a characteristic feature of several bacterial genera, particularly Gram-negative bacteria such as Pseudomonas, Rhizobium, Azotobacter, and Agrobacterium and very rare in Gram-positive bacteria, with exceptions like Enterococcus faecalis.