Question

NADPH/NADP \(^{+}\) is maintained at a high level in cells primarily by A. lactate dehydrogenase. B. the combined actions of glucose 6 -phosphate dehydrogenase and gluconolactonase. C. the action of the electron transport chain. D. exchange with \(\mathrm{NAD}^{+} / \mathrm{NADH}\). E. the combined actions of transketolase and transaldolase.

Short answer

Answer: The primary way cells maintain a high level of NADPH/NADP\(^{+}\) is through the combined actions of glucose 6-phosphate dehydrogenase and gluconolactonase, which are part of the pentose phosphate pathway.

Step-by-step solution

Understand the role of NADPH in cells

NADPH (Nicotinamide Adenine Dinucleotide Phosphate) is a crucial coenzyme in various cell processes, including anabolic reactions, detoxification, and antioxidation. It mainly participates in reduction-oxidation (redox) reactions and helps cells maintain a high level of reduced glutathione.

Analyzing the provided options

Let's examine each choice separately to figure out which one(s) primarily aids in maintaining a high level of NADPH/NADP\(^{+}\) in cells. a. Lactate dehydrogenase: This enzyme helps in the conversion of pyruvate to lactate and vice versa. It primarily deals with NAD\(^{+}\)/NADH, and it doesn't affect the NADPH pool directly. b. Glucose 6-phosphate dehydrogenase and gluconolactonase: These enzymes are part of the pentose phosphate pathway (PPP), generating NADPH from glucose metabolism. c. Electron transport chain: This series of reactions produces ATP but doesn't involve NADPH directly. Instead, it deals with NAD\(^{+}\) and NADH. d. Exchange with NAD\(^{+}\)/NADH: Although NADPH and NADH have similar roles as reducing agents, they do not exchange directly, and their pathways are separate. e. Transketolase and transaldolase: These enzymes also belong to the pentose phosphate pathway. However, they are involved in the non-oxidative phase of the PPP, which does not produce NADPH directly but helps in the conversion of sugar molecules.

Determine the correct choice

From our analysis, we can see that option B, the combined actions of glucose 6-phosphate dehydrogenase and gluconolactonase, primarily help maintain a high level of NADPH/NADP\(^{+}\) in cells. They are part of the pentose phosphate pathway, which is responsible for generating NADPH for various cellular processes.

Key concepts

Pentose Phosphate Pathway

The pentose phosphate pathway (PPP), also known as the hexose monophosphate shunt, is a metabolic pathway that parallels glycolysis, though it serves distinct functions. Unlike glycolysis, which is primarily concerned with energy production in the form of ATP, the PPP focuses on the biosynthesis of nucleotides and the generation of NADPH.

NADPH is a key reducing agent important for protecting the cell against oxidative damage and for providing the reducing power needed in anabolic reactions, such as the synthesis of fatty acids and nucleic acids. The pathway operates in two distinct phases: the oxidative and the non-oxidative phase.

The Oxidative Phase

In the oxidative phase, glucose 6-phosphate is converted to ribulose 5-phosphate. Along this conversion, NADP+ is reduced to NADPH, crucial for anabolic processes. This phase is where glucose 6-phosphate dehydrogenase (G6PD) plays a pivotal role.

The Non-Oxidative Phase

Further, the PPP can enter the non-oxidative phase which restructures carbon skeletons into intermediates that the cell can use for the synthesis of various biomolecules or funnel into glycolysis. Enzymes like transketolase and transaldolase are involved in this phase, though they are not directly responsible for NADPH production.

Glucose 6-Phosphate Dehydrogenase

Glucose 6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme in the oxidative branch of the PPP. Its main function is to catalyze the first step of this pathway, which converts glucose-6-phosphate into 6-phosphoglucono-δ-lactone while reducing NADP+ to NADPH.

The enzymatic activity of G6PD is especially vital for the production of NADPH in cells, as this coenzyme is needed to maintain the reducing environment within the cell. NADPH is used to stave off oxidative stress by regenerating reduced glutathione, which acts as a critical antioxidant. In addition, G6PD deficiency is a known genetic disorder that demonstrates the importance of this enzyme; individuals with the condition are more susceptible to oxidative damage, highlighting the protective role of NADPH produced via G6PD's activity.

Anabolic Reactions

Anabolic reactions are a set of metabolic pathways that construct molecules from smaller units. These reactions are typically endergonic, meaning they require an input of energy. Anabolic processes include the synthesis of complex molecules like proteins, nucleic acids, carbohydrates, and lipids.

The role of NADPH in anabolic reactions is critical as it acts as a reducing agent, donating electrons to the reactions and therefore enabling the biosynthetic processes. For instance, in fatty acid synthesis, NADPH is used to reduce acetyl-CoA, contributing to the building up of larger fat molecules from smaller units. Through its role in anabolic reactions, NADPH plays a fundamental part in cellular growth, repair, and maintenance.

Redox Reactions

Redox reactions, or oxidation-reduction reactions, are chemical reactions that involve the transfer of electrons between species. In the context of cellular biology, these reactions are central to the metabolism, as cells harness energy from redox reactions to perform various functions.

NADPH operates as an electron donor in redox reactions within the cell, making it essential for maintaining cellular redox balance. This balance is integral for protecting cells from reactive oxygen species (ROS) and for ensuring that energy-dependent processes can occur unhindered. NADPH provides the electrons that are needed to reduce glutathione, which in turn reduces peroxides and free radicals, neutralizing them and mitigating oxidative stress.