Select the incorrect statement in reference to Krebs cycle:

Question

Accepted Answer

The correct option is 1:
The correct option is (1) because the statement, "The cycle starts with condensation of acetyl group with pyruvic acid to yield citric acid," is factually incorrect regarding the initiation of the Krebs cycle. This common misconception confuses the reactant entering the cycle with its precursor. The Krebs cycle, which is central to aerobic respiration, officially begins with the condensation of a two-carbon compound, **Acetyl-CoA**, not pyruvic acid. Acetyl-CoA combines with the four-carbon compound, **Oxaloacetate (OAA)**, to form the six-carbon molecule, Citric acid (Citrate), a reaction catalyzed by the enzyme citrate synthase. Pyruvic acid (a three-carbon molecule) is produced during glycolysis and must first undergo an intermediate step called the 'link reaction'—oxidative decarboxylation—to be converted into Acetyl-CoA before it can enter the Krebs cycle. Therefore, stating that pyruvic acid condenses directly to form citric acid makes this option the single incorrect statement among the choices.

The incorrect option is 2:
This statement, "A molecule of GTP is synthesised during conversion of succinyl CoA to succinic acid," is a correct biological fact and therefore an incorrect choice for the question. The conversion of succinyl CoA to succinic acid is the only step in the entire Krebs cycle where direct, substrate-level phosphorylation occurs. This highly energetic thioester bond is cleaved by the enzyme succinyl-CoA synthetase, and the energy released is immediately harnessed to phosphorylate a guanosine diphosphate (GDP) molecule into Guanosine triphosphate (GTP). In certain cell types, this reaction uses ADP instead of GDP to produce an ATP molecule directly. Since GTP is energetically equivalent to ATP and can be readily interconverted, the production of GTP at this step is a true feature of the cycle.

The incorrect option is 3:
The statement, "At one point in the cycle, FAD+ is reduced to FADH2," is a correct depiction of a key redox reaction and thus an incorrect answer. The reduction of the coenzyme Flavin Adenine Dinucleotide (FAD+) to its reduced form, FADH2, occurs only once per turn of the cycle. This step is the conversion of succinate to fumarate, which is catalyzed by the enzyme succinate dehydrogenase. This enzyme is unique because it is embedded within the inner mitochondrial membrane, unlike the other Krebs cycle enzymes found in the mitochondrial matrix. The FADH2 produced here transfers its high-energy electrons directly to the Electron Transport Chain (Complex II), linking the Krebs cycle to the final stage of aerobic respiration.

The incorrect option is 4:
This statement, "NAD+ is reduced to NADH+H+ at three points in the cycle," is fundamentally correct and must be rejected as the answer to the question. The cycle is a major source of reducing power for the cell, and the coenzyme Nicotinamide Adenine Dinucleotide (NAD+) is indeed reduced to NADH + H+ at three distinct oxidative decarboxylation steps. These points are: 1) the conversion of Isocitrate to $\alpha$-Ketoglutarate, 2) the conversion of $\alpha$-Ketoglutarate to Succinyl-CoA, and 3) the final step of the cycle, the conversion of Malate to Oxaloacetate. These three NADH molecules, along with the one FADH2 molecule produced, carry the vast majority of the energy harvested from the acetyl group to the Electron Transport Chain for large-scale ATP generation.