# Respiratory substrates

Respiratory substrates are **organic molecules** that living cells break down in a series of enzyme-controlled steps to **release chemical potential energy**, which is then used to synthesize ATP (adenosine triphosphate). This process is known as respiration. While **glucose** is the primary or "essential" respiratory substrate for most cells, other complex organic molecules can also be used.

**Types of Respiratory Substrates and Their Entry into Respiration**: All carbohydrates, lipids, and proteins can serve as respiratory substrates.

* **Carbohydrates (e.g., Glucose)**:
  * **Glucose** is generally the **main organic molecule** used.
  * It undergoes **glycolysis** in the **cytoplasm**, where it is split into two molecules of pyruvate. Glycolysis produces a net gain of 2 ATP and reduced NAD per glucose molecule.
  * If oxygen is available (aerobic respiration), pyruvate is then **actively transported into the mitochondrial matrix**.
* **Lipids (Fats)**:
  * Lipids are commonly used as respiratory substrates.
  * They are first broken down into **fatty acids and glycerol**.
  * **Glycerol** can be converted into **triose phosphate**, which enters glycolysis.
  * **Fatty acids** are broken down (cut up by enzyme action) into **2-carbon fragments** (acetyl units). These fragments are then fed into the **Krebs cycle via coenzyme A** (acetyl CoA).
  * Vertebrate muscle, including **heart muscle**, is well adapted to respire fatty acids.
* **Proteins**:
  * Proteins can also be used as respiratory substrates, especially by carnivorous animals.
  * They are first **hydrolysed into amino acids**.
  * Individual amino acids undergo **deamination**, where the amino group (–NH2) is split off and excreted (as ammonia or urea).
  * The remaining **carbon compound (organic acid)** then enters the respiratory pathway as **pyruvic acid (pyruvate)**, **acetyl coenzyme A**, or as a **Krebs cycle acid**.
  * Plants rarely respire proteins.

**Energy Values of Respiratory Substrates**: The energy value of respiratory substrates is typically expressed in kilojoules (kJ) per 100g or per gram.

* **Lipids** have a significantly **higher energy density** (kJ/g) than carbohydrates or proteins.
  * Typical values: **3700–4000 kJ per 100g** or **39.4 kJ/g**.
* **Carbohydrates** are intermediate.
  * Typical values: **1600–1760 kJ per 100g** or **15.8 kJ/g**.
* **Proteins** are also intermediate.
  * Typical values: **1700–1720 kJ per 100g** or **17.0 kJ/g**.

This difference in energy value is because most of the energy released in aerobic respiration comes from the **oxidation of hydrogen to water** when reduced NAD and FAD pass electrons to the electron transport chain. Therefore, the **greater the proportion of hydrogen atoms** in a substrate molecule, the more energy it can provide. Lipids have a greater proportion of hydrogen relative to oxygen, making them more highly reduced than sugars.

**Respiratory Quotient (RQ)**: The **Respiratory Quotient (RQ)** is the ratio of the volume of **carbon dioxide produced** to the volume of **oxygen consumed** in a given time during respiration. Calculating the RQ can indicate which substrate is being used.

* **Carbohydrates**: RQ = **1.0** (e.g., C6H12O6 + 6O2 → 6CO2 + 6H2O).
* **Lipids**: RQ = **0.7** (e.g., 2C57H110O6 + 163O2 → 114CO2 + 110H2O). More oxygen is required for fat respiration because fats are more highly reduced.
* **Proteins**: RQ = **0.9**.
* **Anaerobic Respiration**:
  * **Alcoholic fermentation** (in yeast and plants): RQ is theoretically **infinity (∞)** because carbon dioxide is produced but no oxygen is consumed. However, if some aerobic respiration occurs, the RQ will be very high (well above 1).
  * **Lactate fermentation** (in muscle cells): No RQ can be calculated because **no carbon dioxide is produced**.

In practice, an organism rarely respires a single substrate. Many organisms have an RQ between 0.8–0.9, indicating a mix of carbohydrate and fatty acid respiration.

**Specific Substrate Usage**:

* While most cells can use various substrates, **brain cells (neurones) can primarily use only glucose**.
* **Heart muscle preferentially uses fatty acids**.
* Amino acids are generally used as a last resort, as they have more specialized functions.
* In starvation, **proteins** become the major respiratory substrate in mammals.
* For germinating seeds, the RQ can change over time, indicating a shift in the primary respiratory substrate (e.g., from lipids to carbohydrates).Respiratory substrates are **organic molecules** that living cells break down in a series of enzyme-controlled steps to **release chemical potential energy**, which is then used to synthesize ATP (adenosine triphosphate). This process is known as respiration. While **glucose** is the primary or "essential" respiratory substrate for most cells, other complex organic molecules can also be used.

**Types of Respiratory Substrates and Their Entry into Respiration**: All carbohydrates, lipids, and proteins can serve as respiratory substrates.

* **Carbohydrates (e.g., Glucose)**:
  * **Glucose** is generally the **main organic molecule** used.
  * It undergoes **glycolysis** in the **cytoplasm**, where it is split into two molecules of pyruvate. Glycolysis produces a net gain of 2 ATP and reduced NAD per glucose molecule.
  * If oxygen is available (aerobic respiration), pyruvate is then **actively transported into the mitochondrial matrix**.
* **Lipids (Fats)**:
  * Lipids are commonly used as respiratory substrates.
  * They are first broken down into **fatty acids and glycerol**.
  * **Glycerol** can be converted into **triose phosphate**, which enters glycolysis.
  * **Fatty acids** are broken down (cut up by enzyme action) into **2-carbon fragments** (acetyl units). These fragments are then fed into the **Krebs cycle via coenzyme A** (acetyl CoA).
  * Vertebrate muscle, including **heart muscle**, is well adapted to respire fatty acids.
* **Proteins**:
  * Proteins can also be used as respiratory substrates, especially by carnivorous animals.
  * They are first **hydrolysed into amino acids**.
  * Individual amino acids undergo **deamination**, where the amino group (–NH2) is split off and excreted (as ammonia or urea).
  * The remaining **carbon compound (organic acid)** then enters the respiratory pathway as **pyruvic acid (pyruvate)**, **acetyl coenzyme A**, or as a **Krebs cycle acid**.
  * Plants rarely respire proteins.

**Energy Values of Respiratory Substrates**: The energy value of respiratory substrates is typically expressed in kilojoules (kJ) per 100g or per gram.

* **Lipids** have a significantly **higher energy density** (kJ/g) than carbohydrates or proteins.
  * Typical values: **3700–4000 kJ per 100g** or **39.4 kJ/g**.
* **Carbohydrates** are intermediate.
  * Typical values: **1600–1760 kJ per 100g** or **15.8 kJ/g**.
* **Proteins** are also intermediate.
  * Typical values: **1700–1720 kJ per 100g** or **17.0 kJ/g**.

This difference in energy value is because most of the energy released in aerobic respiration comes from the **oxidation of hydrogen to water** when reduced NAD and FAD pass electrons to the electron transport chain. Therefore, the **greater the proportion of hydrogen atoms** in a substrate molecule, the more energy it can provide. Lipids have a greater proportion of hydrogen relative to oxygen, making them more highly reduced than sugars.

**Respiratory Quotient (RQ)**: The **Respiratory Quotient (RQ)** is the ratio of the volume of **carbon dioxide produced** to the volume of **oxygen consumed** in a given time during respiration. Calculating the RQ can indicate which substrate is being used.

* **Carbohydrates**: RQ = **1.0** (e.g., C6H12O6 + 6O2 → 6CO2 + 6H2O).
* **Lipids**: RQ = **0.7** (e.g., 2C57H110O6 + 163O2 → 114CO2 + 110H2O). More oxygen is required for fat respiration because fats are more highly reduced.
* **Proteins**: RQ = **0.9**.
* **Anaerobic Respiration**:
  * **Alcoholic fermentation** (in yeast and plants): RQ is theoretically **infinity (∞)** because carbon dioxide is produced but no oxygen is consumed. However, if some aerobic respiration occurs, the RQ will be very high (well above 1).
  * **Lactate fermentation** (in muscle cells): No RQ can be calculated because **no carbon dioxide is produced**.

In practice, an organism rarely respires a single substrate. Many organisms have an RQ between 0.8–0.9, indicating a mix of carbohydrate and fatty acid respiration.

**Specific Substrate Usage**:

* While most cells can use various substrates, **brain cells (neurones) can primarily use only glucose**.
* **Heart muscle preferentially uses fatty acids**.
* Amino acids are generally used as a last resort, as they have more specialized functions.
* In starvation, **proteins** become the major respiratory substrate in mammals.
* For germinating seeds, the RQ can change over time, indicating a shift in the primary respiratory substrate (e.g., from lipids to carbohydrates).