Question

After a person has ingested large amounts of sucrose, the body transforms the glucose and fructose that exceed caloric requirements to fatty acids for triacylglycerol synthesis. This fatty acid synthesis consumes acetyl-CoA, ATP, and NADPH. How do cells produce acetyl-CoA, ATP, and NADPH from glucose?

Short answer

Cells convert glucose to acetyl-CoA via glycolysis and pyruvate processing. ATP is mainly produced via glycolysis and oxidative phosphorylation. NADPH is generated through the pentose phosphate pathway.

Step-by-step solution

Glucose to Acetyl-CoA

First, glucose undergoes glycolysis, a ten-step process that takes place in the cytoplasm. During glycolysis, one molecule of glucose (a 6-carbon sugar) is converted into two molecules of pyruvate (each with 3 carbons). Pyruvate is then transported into the mitochondria, where it is converted into acetyl-CoA by the pyruvate dehydrogenase complex. This conversion process results in the production of acetyl-CoA and the release of CO2.

Production of ATP through Glycolysis and Cellular Respiration

ATP is generated primarily through glycolysis and the subsequent steps in the mitochondria. In glycolysis, a small amount of ATP is produced directly. However, more ATP is generated in the mitochondria through oxidative phosphorylation. Acetyl-CoA enters the citric acid cycle (Krebs cycle), where it generates NADH and FADH2, which carry electrons to the electron transport chain. The energy from electrons is used to drive ATP synthesis, producing the majority of the ATP.

Generation of NADPH via Pentose Phosphate Pathway

To generate NADPH from glucose, cells use the pentose phosphate pathway, which occurs in the cytoplasm. This pathway branches off from glycolysis and primarily serves to produce NADPH and ribose-5-phosphate. For each glucose molecule affected, two NADPH molecules are generated, which are crucial for biosynthetic reactions, including fatty acid synthesis.

Key concepts

Glycolysis

Glycolysis is the first step in breaking down glucose to produce energy. This process occurs in the cytoplasm and involves a series of ten enzyme-catalyzed reactions. During glycolysis, one glucose molecule (which has six carbon atoms) is converted into two molecules of pyruvate, each containing three carbon atoms. This process yields a net gain of two ATP molecules and two NADH molecules. Glycolysis is an anaerobic process, meaning it doesn’t require oxygen, and it provides the energy needed for cells when oxygen is scarce.

Citric Acid Cycle

The Citric Acid Cycle, also known as the Krebs Cycle, is a central part of cellular respiration. This process occurs in the mitochondria and begins with acetyl-CoA, which is produced from pyruvate after glycolysis. Each acetyl-CoA molecule enters the cycle and combines with oxaloacetate to form citrate. Through a series of enzymatic reactions, citrate is eventually converted back to oxaloacetate. In the process, ATP, NADH, and FADH2 are produced, along with the release of CO2. The NADH and FADH2 carry electrons to the electron transport chain, driving the production of ATP.

Pentose Phosphate Pathway

The Pentose Phosphate Pathway (PPP) is a metabolic pathway parallel to glycolysis. It takes place in the cytoplasm and serves two major functions: the production of NADPH and the synthesis of ribose-5-phosphate. NADPH is a reducing agent essential for biosynthetic reactions, such as fatty acid synthesis. The pathway begins with glucose-6-phosphate, a product of glycolysis, which is oxidized to generate NADPH. Ribose-5-phosphate is used in nucleotide biosynthesis. For every glucose molecule processed through PPP, two molecules of NADPH are generated.

Acetyl-CoA

Acetyl-CoA is a vital molecule in many metabolic pathways. It is primarily formed from pyruvate in the mitochondria during the transition step from glycolysis to the citric acid cycle. The enzyme complex known as pyruvate dehydrogenase catalyzes this conversion, releasing a molecule of CO2 in the process. Acetyl-CoA is not only crucial for energy production through the citric acid cycle but also serves as a building block for the synthesis of fatty acids. It acts as a two-carbon donor in various biosynthetic reactions, linking carbohydrate metabolism to lipid metabolism.

NADPH

NADPH is an important cofactor in anabolic reactions, providing the necessary reducing power for biosynthesis. It is mainly generated through the pentose phosphate pathway. Unlike NADH that is used in energy production, NADPH supplies electrons in biosynthetic processes, such as fatty acid and cholesterol synthesis. It also plays a crucial role in maintaining the antioxidant system of the cell, helping to combat oxidative stress by regenerating reduced glutathione, an important cellular antioxidant.

ATP Production

ATP, or adenosine triphosphate, is often referred to as the energy currency of the cell. Cells generate ATP through a combination of glycolysis, the citric acid cycle, and oxidative phosphorylation in the electron transport chain. Although glycolysis provides a modest amount of ATP, the majority is produced during oxidative phosphorylation, where the energy from NADH and FADH2 generated in previous steps is used to synthesize ATP. ATP is vital for numerous cellular processes, providing energy for mechanical work, active transport, and biosynthetic reactions.