Question

Alcohol intoxication can lead to hypoglycemia especially if the alcohol is consumed by an undernourished individual or after strenuous exercise. In both cases the hypoglycemia results from the inhibitory effects of alcohol on hepatic gluconcogenesis and occurs under circumstances of heparic glycogen depletion. Alcohol potentiates the hypoglycemic effect of insulin so diaberics who have self-administered insulin and then consumed alcohol are at increased risk. Alcohol metabolism produces large amounts of NADH which inhibit gluconcogenesis by A. shifting the pyruvate-lactate cquilibrium toward lactate. B. favoring the production of oxaloacetate from malate. C. preventing the movement of phosphocaolpyruvate from the mitochondria to the cytasol. D. inhibiting the electron transport chain. E. inhibiting the malate-aspartate shurtle.

Short answer

Answer: The metabolism of alcohol produces large amounts of NADH by converting ethanol to acetaldehyde via the enzyme alcohol dehydrogenase (ADH). This high NADH/NAD+ ratio inhibits gluconeogenesis by shifting the pyruvate-lactate equilibrium towards lactate production, preventing pyruvate from being used for gluconeogenesis.

Step-by-step solution

Brief overview of gluconeogenesis

Gluconeogenesis is a metabolic pathway that allows the production of glucose from certain non-carbohydrate precursors such as lactate, glycerol, and some amino acids. This pathway is crucial for maintaining blood glucose levels during fasting or intense exercise.

NADH formation during alcohol metabolism

When alcohol (ethanol) is metabolized in the liver, it gets converted into acetaldehyde by the enzyme alcohol dehydrogenase (ADH). This process leads to the production of NADH from NAD+. Higher levels of NADH inhibit gluconeogenesis by affecting multiple steps in the pathway. Now, let us assess the given options:

Evaluate option A

A high NADH/NAD+ ratio shifts the pyruvate-lactate equilibrium towards lactate production (by lactate dehydrogenase). Lactate accumulation prevents pyruvate from being used for gluconeogenesis. So, option A is a correct explanation for the inhibition of gluconeogenesis by NADH.

Evaluate option B

Option B states that NADH production favors the conversion of malate into oxaloacetate. However, this statement is incorrect. A high NADH/NAD+ ratio actually inhibits the conversion of malate to oxaloacetate, which is required for gluconeogenesis.

Evaluate option C

Option C suggests that NADH prevents the movement of phosphoenolpyruvate (PEP) from the mitochondria to the cytosol. While it is true that mitochondrial PEP has to be transported into the cytosol for gluconeogenesis, the process is not directly affected by NADH levels. Hence, option C is incorrect.

Evaluate option D

Option D indicates that NADH inhibits the electron transport chain (ETC). While NADH is a key electron donor in the ETC, an excess of NADH does not directly inhibit the ETC. Thus, option D is incorrect concerning the inhibition of gluconeogenesis.

Evaluate option E

Option E states that the malate-aspartate shuttle is inhibited by NADH. This shuttle helps to transfer reducing equivalents from the cytosol to the mitochondria. Although a high NADH/NAD+ ratio can affect the shuttle's efficiency, it is not the primary reason for the inhibition of gluconeogenesis by alcohol metabolism. So, option E is not the most suitable choice.

Choose the best explanation

As analyzed in the previous steps, option A, which suggests that NADH inhibits gluconeogenesis by shifting the pyruvate-lactate equilibrium towards lactate, is the most accurate explanation for the given exercise.