# The Role of Coenzymes ## Coenzyme A - A coenzyme is a molecule that assists an enzyme in carrying out its function but is not consumed in the reaction itself - Coenzyme A (CoA) consists of: - A nucleoside (ribose and adenine) - A vitamin component - During the link reaction, CoA binds to the acetyl group (2C) - the remainder of the pyruvate molecule after decarboxylation - to form acetyl CoA - Acetyl CoA then delivers the acetyl group to the Krebs cycle where it is used to continue aerobic respiration - This represents a critical bridging stage that: - Brings the products of carbohydrate breakdown (or lipid/amino acid breakdown) into the later stages of respiration - Links the initial cytoplasmic stage of respiration to the mitochondrial stages

Coenzyme A transfers acetyl groups from the link reaction to the Krebs cycle by forming acetyl CoA

## NAD & FAD as Hydrogen Carriers - Coenzymes NAD and FAD play essential roles in aerobic respiration as **hydrogen carriers** - When hydrogen atoms become available at various points during respiration, NAD and FAD accept these hydrogen atoms - A hydrogen atom consists of: - One hydrogen ion ($\text{H}^+$) - One electron ($\text{e}^-$) ### Reduction of coenzymes - When the coenzymes gain hydrogen they are **reduced** - NAD becomes reduced NAD (NADH) - FAD becomes reduced FAD ($\text{FADH}_2$) - OIL RIG: **O**xidation **I**s **L**oss, **R**eduction **I**s **G**ain

Think of NAD and FAD as molecular taxis - they pick up hydrogen passengers at different stages of respiration and deliver them to the electron transport chain

### Transfer to the electron transport chain - Reduced coenzymes transfer the hydrogen atoms (hydrogen ions and electrons) from the different stages of respiration to the **electron transport chain** on the inner mitochondrial membrane - At the electron transport chain, the hydrogen atoms are removed from the coenzymes - When the hydrogen atoms are removed, the coenzymes are **oxidised** back to NAD and FAD - This regeneration allows them to be reused in further cycles of respiration ### Role in ATP synthesis - Hydrogen ions and electrons are crucial in the electron transport chain for ATP synthesis - **Electrons** from reduced NAD (NADH) and reduced FAD ($\text{FADH}_2$) are passed to the electron transport chain - **Hydrogen ions** from reduced NAD (NADH) and reduced FAD ($\text{FADH}_2$) are released when the electrons are lost - The electron transport chain uses energy from the electrons to pump hydrogen ions (protons) across the inner mitochondrial membrane into the intermembrane space - This creates a **proton gradient** (higher concentration of hydrogen ions in the intermembrane space than in the matrix) - Movement of hydrogen ions down the proton gradient, back into the mitochondrial matrix through ATP synthase, provides the energy required for **ATP synthesis**

Without NAD and FAD to transport hydrogens, the electron transport chain cannot function and ATP production stops

## Sources of Reduced NAD & FAD - A specific amount of reduced NAD and reduced FAD is produced during the aerobic respiration of a single glucose molecule - These amounts can be tracked through each stage of respiration ### Reduced NAD production - **Glycolysis**: $2 \times 1 = 2$ reduced NAD molecules - One molecule produced per triose phosphate - Two triose phosphates produced per glucose molecule - **Link Reaction**: $2 \times 1 = 2$ reduced NAD molecules - One molecule produced per pyruvate - Two pyruvate molecules produced per glucose molecule - **Krebs Cycle**: $2 \times 3 = 6$ reduced NAD molecules - Three molecules produced per turn of the cycle - The cycle turns twice per glucose molecule - **Total**: 10 reduced NAD molecules per glucose molecule ### Reduced FAD production - **Krebs Cycle**: $2 \times 1 = 2$ reduced FAD molecules - One molecule produced per turn of the cycle - The cycle turns twice per glucose molecule - **Total**: 2 reduced FAD molecules per glucose molecule

Remember the doubling: since one glucose molecule splits into two triose phosphates in glycolysis, everything after that point occurs twice per glucose molecule

### Summary table | **Stage of Respiration** | **Reduced NAD** | **Reduced FAD** | |--------------------------|-----------------|-----------------| | Glycolysis | 2 | 0 | | Link Reaction | 2 | 0 | | Krebs Cycle | 6 | 2 | | **Total per glucose** | **10** | **2** | ### Visual comparison of coenzyme production The chart below visualizes the production of reduced NAD and reduced FAD at each stage of aerobic respiration, clearly showing that the Krebs cycle is the major source of both coenzymes:

### Why doubling occurs - One glucose molecule is split into two triose phosphate molecules during glycolysis - Each triose phosphate produces one pyruvate molecule - Each pyruvate molecule enters the link reaction once - Each acetyl CoA enters the Krebs cycle once - Therefore all reactions after the splitting of glucose occur **twice per glucose molecule** ## The Importance of Hydrogen Content - The number of reduced coenzymes produced directly affects the amount of ATP that can be synthesized - More hydrogen atoms available = more reduced NAD and FAD produced - More reduced coenzymes = larger proton gradient across the mitochondrial membrane - Larger proton gradient = more ATP produced via chemiosmosis - This explains why different respiratory substrates (carbohydrates, lipids, proteins) have different energy values - Molecules with higher hydrogen content (like lipids with long hydrocarbon chains) yield more ATP when respired

The proton gradient created by hydrogen transport is the driving force behind ATP synthesis through chemiosmosis

## Oxidation and Reduction in Context $$\text{NAD} + 2\text{H} \xrightarrow{\text{REDUCTION}} \text{NADH} + \text{H}^+$$ $$\text{NADH} + \text{H}^+ \xrightarrow{\text{OXIDATION}} \text{NAD} + 2\text{H}$$ $$\text{FAD} + 2\text{H} \xrightarrow{\text{REDUCTION}} \text{FADH}_2$$ $$\text{FADH}_2 \xrightarrow{\text{OXIDATION}} \text{FAD} + 2\text{H}$$ - These reactions are reversible, allowing the coenzymes to be recycled throughout respiration - The continual oxidation and reduction of these coenzymes is essential for maintaining the flow of energy through the respiratory pathway