Question

An inability to renxidize NADH because of the defect of complex I would A. inhibit isocitrate dehydrogenase and, therefore, inhibit the rate of the TCA cycle. B. force the oxaloacetate-malate equilibrium toward oxaloacetate. C. promote the \(\alpha\) -glycerol phosphate shuttle for transporting reducing equivalents. D. cause NADH to freely diffuse from the mitochondria to the cytosol. E. force the succinate-fumarate equilibrium toward succinate.

Short answer

Answer: The most immediate effect is to inhibit isocitrate dehydrogenase and, therefore, inhibit the rate of the TCA cycle.

Step-by-step solution

Understand the NADH and role of complex I in ETC

NADH is an essential electron carrier that moves electrons from one reaction to another in various metabolic pathways, especially in the ETC (electrogen transport chain). Complex I (NADH-CoQ oxidoreductase) is the first enzyme of the mitochondrial ETC, which accepts electrons from NADH and transfers them to CoQ (coenzyme Q).

Analyze the effects of defective complex I

When the complex I is defective (inhibited), NADH cannot be reoxidized to NAD+. As a result, NADH accumulates in the cell, while the NAD+ level decreases. This disrupts the NAD+/NADH balance and has a cascading effect on various cellular processes.

Evaluate each given choice

A. inhibit isocitrate dehydrogenase and, therefore, inhibit the rate of the TCA cycle. - True. NAD+ is required for the isocitrate dehydrogenase step in the TCA cycle, and the decrease in NAD+ levels due to the defective complex I can inhibit the rate of the TCA cycle. B. force the oxaloacetate-malate equilibrium toward oxaloacetate. - False. The oxaloacetate-malate equilibrium is not directly affected by the complex I defect. C. promote the \(\alpha\) -glycerol phosphate shuttle for transporting reducing equivalents. - True. The \(\alpha\)-glycerol phosphate shuttle is an alternative way to indirectly transfer electrons from NADH in the cytosol to the ETC in mitochondria. When the complex I is defective, this shuttle can be upregulated to compensate for the lost function of complex I. D. cause NADH to freely diffuse from the mitochondria to the cytosol. - False. NADH cannot freely diffuse across the mitochondrial inner membrane, regardless of whether complex I is functional or not. E. force the succinate-fumarate equilibrium toward succinate. - False. The succinate-fumarate equilibrium is not directly affected by the complex I defect.

Choose the correct answer

Both options A and C are correct based on our analysis. However, since this is a multiple-choice question and only one answer can be selected, we need to choose the option that best describes the most immediate effect of complex I defect: A. inhibit isocitrate dehydrogenase and, therefore, inhibit the rate of the TCA cycle.