Test: Krebs (citric acid) cycle and oxidative phosphorylation - MCAT MCQ

During glucose metabolism, a single molecule of glucose produces two molecules of pyruvate through the process of glycolysis. Each pyruvate molecule then undergoes conversion to acetyl CoA before entering the Krebs cycle. Since there are two pyruvate molecules produced from one glucose molecule, the answer is 2 molecules of acetyl CoA.

During the citric acid cycle, the oxidation of acetyl CoA leads to the production of reducing equivalents in the form of NADH and FADH₂. These molecules carry high-energy electrons that are extracted from the citric acid cycle and then delivered to the electron transport chain (ETC). NAD⁺ and FAD act as electron carriers and are reduced to NADH and FADH₂, respectively, by accepting the electrons generated during the cycle. These reduced forms of NAD and FAD then donate the electrons to the ETC for further energy generation.

Explanation: NADH is a high-energy electron carrier that is generated during the oxidation of glucose in processes like glycolysis and the citric acid cycle. In the citric acid cycle, NADH is produced during the oxidation of isocitrate to α-ketoglutarate and during the oxidation of α-ketoglutarate to succinyl-CoA. High cellular concentrations of NADH can inhibit the entry of pyruvate into the citric acid cycle through negative feedback regulation. This occurs because the accumulation of NADH signals that the cell has sufficient energy and doesn't require further oxidation of pyruvate to generate more NADH through the citric acid cycle. As a result, the entry of pyruvate into the cycle is inhibited.

The activity of the electron transport chain and oxidative phosphorylation is closely linked to the cellular energy demands. When the cell requires more ATP, the electron transport chain and oxidative phosphorylation are stimulated. One of the key factors influencing their activity is the concentration of ADP (adenosine diphosphate). ADP is converted to ATP through the phosphorylation process in oxidative phosphorylation. When ADP levels are high, it indicates that ATP levels are low, signaling a need for increased ATP production. This stimulates the electron transport chain to transfer electrons and generate a proton gradient, which in turn drives ATP synthesis. Therefore, high ADP concentrations favor increased activity of the electron transport chain and oxidative phosphorylation.

The relative pH levels of the cytosol, intermembrane space of the mitochondria, and the mitochondrial matrix differ. The mitochondrial matrix has a higher pH than both the cytosol and the intermembrane space. This is because the electron transport chain and chemiosmosis during oxidative phosphorylation lead to the pumping of protons from the mitochondrial matrix to the intermembrane space. This creates a higher concentration of protons and a lower pH in the intermembrane space compared to the mitochondrial matrix. The protons then flow back into the mitochondrial matrix through ATP synthase, which leads to the synthesis of ATP. This process results in a higher concentration of protons and a lower pH in the intermembrane space compared to the mitochondrial matrix. Finally, the cytosol, which is outside the mitochondria, typically has a higher pH than both the intermembrane space and the mitochondrial matrix.

The superoxide anion is produced as a byproduct of various metabolic processes within the body. These processes include oxidative phosphorylation in the mitochondria, enzymatic reactions, and cellular respiration. During these processes, electrons can be incompletely transferred, leading to the formation of the superoxide anion. Additionally, certain enzymes, such as NADPH oxidase, can generate superoxide as part of their normal function. It is important to note that while the superoxide anion is a reactive oxygen species and can have damaging effects, the body has defense mechanisms, including antioxidant enzymes, to neutralize and manage the levels of reactive oxygen species.

Although the Krebs cycle is involved in the production of ATP indirectly through oxidative phosphorylation, ATP itself is not a direct product of the Krebs cycle. The primary products of the Krebs cycle are NADH, FADH2, and carbon dioxide.

In oxidative phosphorylation, the energy released during electron transport is utilized to generate ATP. The proton gradient established across the inner mitochondrial membrane drives the synthesis of ATP by ATP synthase, which converts ADP (adenosine diphosphate) to ATP (adenosine triphosphate).

NADH is produced directly in the Krebs cycle. It is generated during the redox reactions that occur as the cycle progresses. NADH is an important electron carrier that will be used in the electron transport chain for ATP production.

ATP synthase is an enzyme complex that plays a crucial role in oxidative phosphorylation. It utilizes the proton gradient generated by the electron transport chain to produce ATP from ADP and inorganic phosphate. ATP synthase acts as a molecular machine that converts the potential energy stored in the proton gradient into the chemical energy of ATP.