Question

After an overnight fast, which of the following enzymes would be expected to have little, if any, physiological activity? (A) Malate dehydrogenase (B) Glucokinase (C) ?-Ketoglutarate dehydrogenase (D) Phosphofructokinase-1

Short answer

B) Glucokinase

Step-by-step solution

- Understand the context of fasting

After an overnight fast, the body is in a state of low blood glucose levels and therefore, it relies on alternative metabolic pathways like gluconeogenesis and glycogenolysis to maintain blood glucose.

- Identify the role of each enzyme

Evaluate the function of each enzyme in the context of fasting:(A) Malate dehydrogenase - involved in the citric acid cycle.(B) Glucokinase - catalyzes the first step of glycolysis by converting glucose to glucose-6-phosphate.(C) ?-Ketoglutarate dehydrogenase - involved in the citric acid cycle.(D) Phosphofructokinase-1 - regulates the third step of glycolysis by converting fructose-6-phosphate to fructose-1,6-bisphosphate.

- Determine which pathways are active during fasting

During fasting, glycolysis is downregulated because glucose levels are low and the body focuses on producing glucose through gluconeogenesis and freeing glucose from glycogen stores (glycogenolysis).

- Identify enzymes active during gluconeogenesis

Malate dehydrogenase and ?-Ketoglutarate dehydrogenase, both involved in the citric acid cycle, remain active to provide substrates for gluconeogenesis.

- Determine enzyme inactivity

Glucokinase and Phosphofructokinase-1 are glycolytic enzymes and would have little, if any, activity during fasting. Among these, Glucokinase specifically has very little activity since its main role is in the liver for glycolysis when glucose is abundant.

- Select the correct answer

Based on the analysis, Glucokinase would have the least physiological activity after an overnight fast.

Key concepts

fasting state metabolism

When we talk about fasting state metabolism, we refer to the body's way of maintaining energy and glucose levels when food intake is minimal, such as after an overnight fast. During fasting, the body experiences low blood glucose levels. To counter this, it switches to alternative metabolic pathways: namely, gluconeogenesis and glycogenolysis.
Gluconeogenesis is the process of generating glucose from non-carbohydrate sources, while glycogenolysis breaks down glycogen store in the liver to release glucose into the bloodstream.
In this state, glycolysis (the breakdown of glucose) is downregulated, as the body prefers to conserve what little glucose is available and, instead, produce its own through gluconeogenesis. Important hormones like glucagon play a significant role in signaling this metabolic shift from glucose storage and utilization to glucose production and release.
In summary, fasting state metabolism focuses on providing glucose when dietary sources are unavailable, primarily through gluconeogenesis and glycogenolysis.

enzyme function

Enzymes play a crucial role in regulating metabolic pathways. They are biological catalysts that speed up reactions without being consumed. Each enzyme is specific to a particular reaction and can be highly regulated by the body to ensure metabolic balance.
During the fasting state, enzymes that facilitate glucose production and release, like those in gluconeogenesis and glycogenolysis, are upregulated. Conversely, enzymes involved in glycolysis, the pathway for breaking down glucose, are downregulated.
For example, Glucokinase and Phosphofructokinase-1 are key glycolytic enzymes, meaning they are active when glucose is plentiful. However, in the fasting state, their activity significantly decreases as the demand for glycolysis drops. This precise regulation ensures efficient use of energy resources and maintains blood glucose levels within a healthy range.

glycolysis

Glycolysis is the metabolic pathway that breaks down glucose to produce energy. It consists of ten steps and occurs in the cytoplasm of cells. The pathway can be divided into two phases: the energy investment phase and the energy payoff phase.
In the energy investment phase, the cell uses ATP to convert glucose into fructose-1,6-bisphosphate. Key enzymes like Glucokinase and Phosphofructokinase-1 catalyze these early steps.
In the energy payoff phase, the pathway generates ATP and pyruvate. While glycolysis is crucial for providing quick energy, its activity drops during fasting when glucose levels are low. The body then relies more on pathways like gluconeogenesis to maintain energy and glucose levels. This regulation ensures that the cells have a constant energy supply, even when food intake is limited.

gluconeogenesis

Gluconeogenesis is the metabolic process of generating glucose from non-carbohydrate sources, such as amino acids, lactate, and glycerol. This pathway primarily occurs in the liver and partially in the kidneys, helping maintain blood glucose levels during prolonged fasting or intense exercise.
Key enzymes in gluconeogenesis include Pyruvate Carboxylase, Phosphoenolpyruvate Carboxykinase, and Glucose-6-phosphatase. These enzymes catalyze reactions that reverse the steps of glycolysis. For instance, Pyruvate Carboxylase converts pyruvate into oxaloacetate, an essential intermediate for glucose production.
During fasting, the body's priority is to ensure a steady supply of glucose to vital organs, like the brain. By activating gluconeogenesis, the liver can produce and release glucose into the bloodstream, thus maintaining energy levels and proper physiological function.
In essence, gluconeogenesis is a life-sustaining pathway that kicks in when dietary glucose is unavailable, converting various substrates into glucose to keep the body functioning optimally.