Question

How does the yield of ATP from complete oxidation of one molecule of glucose in muscle and brain differ from that in liver, heart, and kidney? What is the underlying reason for this difference?

Short answer

Muscle and brain yield 30 ATP, while liver, heart, and kidney yield 32 ATP due to different NADH shuttle systems.

Step-by-step solution

Understand the Basic Pathways of Glucose Metabolism

Glucose undergoes glycolysis in the cytoplasm to form pyruvate, which enters mitochondria and is converted to acetyl-CoA. Acetyl-CoA then enters the Krebs cycle. NADH and FADH2 produced through these processes donate electrons to the Electron Transport Chain (ETC) to produce ATP.

Calculate ATP Yield from Glycolysis

From one molecule of glucose during glycolysis, 2 molecules of ATP and 2 molecules of NADH are produced.

Consider NADH Transport into Mitochondria

NADH molecules produced in the cytoplasm during glycolysis must be transported into the mitochondria. This transport happens through two main shuttle systems: the Glycerol 3-Phosphate Shuttle (in muscle and brain) and the Malate-Aspartate Shuttle (in liver, heart, and kidney).

Glycerol 3-Phosphate Shuttle in Muscle and Brain

This shuttle transfers electrons from NADH to FAD in the mitochondria, resulting in the production of FADH2, which enters the ETC and produces 1.5 ATP per molecule of FADH2.

Malate-Aspartate Shuttle in Liver, Heart, and Kidney

The Malate-Aspartate Shuttle effectively transfers electrons from NADH in the cytoplasm to NADH in the mitochondria, resulting in the generation of 2.5 ATP per molecule of NADH.

Calculate Total ATP Yield

In muscle and brain: From glycolysis, 2 ATP (directly) + 2 NADH (via Glycerol 3-Phosphate Shuttle = 3 ATP) = 5 ATP. Additionally, through the Krebs cycle, each glucose molecule produces 2 ATP (GTP), 6 NADH (15 ATP), and 2 FADH2 (3 ATP), leading to 20 ATP from one cycle. Total yield is 5 (glycolysis) + 20 (Krebs) = 30 ATP. In liver, heart, and kidney: From glycolysis, 2 ATP (directly) + 2 NADH (via Malate-Aspartate Shuttle = 5 ATP) = 7 ATP. From the Krebs cycle, each glucose molecule produces 20 ATP as mentioned before. Total yield is 7 (glycolysis) + 20 (Krebs) = 32 ATP.

Summarize the Difference

The yield of ATP from the complete oxidation of one molecule of glucose is 30 ATP in muscle and brain, and 32 ATP in liver, heart, and kidney. The underlying reason for this difference is the different shuttle mechanisms used to transport NADH into the mitochondria: the Glycerol 3-Phosphate Shuttle in muscle and brain, and the Malate-Aspartate Shuttle in liver, heart, and kidney.

Key concepts

Glucose metabolism

Glucose metabolism is the process where glucose is broken down in the cells to release energy. It begins with **glycolysis**, which takes place in the cytoplasm. Here, one molecule of glucose (a six-carbon sugar) is split into two molecules of pyruvate (a three-carbon compound). During glycolysis, **2 ATP** and **2 NADH** molecules are produced.

After glycolysis, pyruvate enters the mitochondria and is converted into **Acetyl-CoA**, which then enters the **Krebs cycle** (also known as the citric acid cycle). The Krebs cycle produces more energy carriers: **6 NADH**, **2 FADH2**, and **2 ATP** (per glucose molecule). These energy carriers are essential for the next step - the **Electron Transport Chain (ETC)**.

Understanding the ATP yield differences in various tissues is crucial because not all tissues metabolize glucose in the same way.

Glycerol 3-Phosphate Shuttle

The Glycerol 3-Phosphate Shuttle is one of the two main shuttle systems that transport NADH from the cytoplasm into the mitochondria. This shuttle is used by muscles and the brain. Here's how it works:

• Cytoplasmic NADH donates its electrons to dihydroxyacetone phosphate (DHAP), converting it into **Glycerol 3-Phosphate**.


• Glycerol 3-Phosphate enters the mitochondria and transfers its electrons to FAD, forming **FADH2**.


• FADH2 then enters the Electron Transport Chain and contributes to ATP production.

However, each molecule of FADH2 generates only **1.5 ATP**, which is less than the amount generated by NADH when using the Malate-Aspartate Shuttle. This results in a lower total ATP yield from glycolysis in tissues employing the Glycerol 3-Phosphate Shuttle.

Malate-Aspartate Shuttle

The Malate-Aspartate Shuttle operates in tissues such as the liver, heart, and kidneys and is more efficient at generating ATP. This shuttle involves a two-step process:

• First, cytoplasmic NADH transfers its electrons to oxaloacetate, forming **Malate**.


• Malate can cross into the mitochondria, where it donates the electrons back to NAD+, thus regenerating **NADH**.

Since NADH directly enters the Electron Transport Chain, each NADH generates **2.5 ATP**. This higher efficiency results in a greater ATP yield in tissues using this shuttle, compared to those using the Glycerol 3-Phosphate Shuttle.

Electron Transport Chain (ETC)

The Electron Transport Chain (ETC) is a series of protein complexes located in the inner mitochondrial membrane. The ETC is the final step of aerobic respiration and is where the majority of ATP is produced. Here’s how it works:

• NADH and FADH2 donate electrons to the electron transport chain. These electrons move through various protein complexes.


• The transfer of electrons drives the pumping of protons (H+) from the matrix to the intermembrane space, creating a proton gradient.


• The flow of protons back into the mitochondrial matrix through **ATP synthase** drives the synthesis of ATP from ADP and inorganic phosphate (Pi).

Ultimately, the electrons combine with oxygen and protons to form water. This process, known as **oxidative phosphorylation**, generates a significant amount of ATP, crucial for cell functions.

Understanding these processes clarifies why ATP yield can differ in various tissues, based on which shuttle system they use and the efficiency of the ETC.