Help with the Krebs Cycle - GRE Subject Test: Biochemistry, Cell, and Molecular Biology

The Krebs cycle is responsible for creating three molecules of NADH, and one molecule of both ATP and NADH. Acetyl CoA is the 2-carbon molecule that enters the Krebs cycle following pyruvate decarboxylation.

Each of the enzymes is involved in the citric acid cycle except for phosphoglycerate kinase, which is an enzyme that is utilized in glycolysis and gluconeogenesis, and catalyzes the reversible transfer or a phosphate group from 1,3-bisphosphoglycerate to ADP, producing and/or consuming 3-phosphoglycerate and ATP.

Gluconeogenesis is the process in which glucose can be generated from carbon structures that are not the canonical carbohydrate inputs. This is required for many organisms to maintain appropriate blood glucose levels, and for vertebrates gluconeogenesis primarily occurs in the liver, although it has been found to occur in the kidneys as well.

The end product of glycolysis is two molecules of pyruvate, however the molecule used to starts the Krebs cycle is acetyl-CoA. Before going into the Krebs cycle then these 2 pyruvate molecules need to be converted into 2 acetyl-CoA molecules via pyruvate dehydrogenase complex, which occurs in the mitochondria and releases carbon dioxide.

During glycolysis, 2 molecules of NADH are produced per glucose. During the Krebs cycle, 3 molecules of NADH are produced per acetyl-CoA. With 2 molecules of glucose, glycolysis can run twice and produce 4 molecules of acetyl-CoA. Since 2 pyruvates are produced from glucose during glycolysis, a total of 4 are made from our 2 glucose molecules. These 4 pyruvates are then converted to 4 acetyl-CoA molecules. Each of these acteyl-CoA molecules runs through the Krebs cycle yielding a total 12 molecules of NADH. 4 from glycolysis, 12 from the TCA cycle so 16 molecules of NADH total.

Each turn of Krebs cycle produces 3 NADH and 1 ATP. Recall that each turn of Krebs cycle requires a molecule of acetyl-CoA (two-carbon molecule). Acetyl-CoA comes from pyruvate, which in turn comes from glucose. During glycolysis, a molecule of glucose (six-carbon molecule) is converted into two pyruvate molecules; therefore, a molecule of glucose will eventually lead to two acetyl-CoA molecules. This means that there are two turns of Krebs cycle for every glucose molecule and, therefore, for a given molecule of glucose Krebs cycle produces 6 NADH and 2 ATP.

Glycolysis produces a net of 2 ATP and 2 NADH; therefore, Krebs cycle produces three times the NADH and the same amount of ATP as glycolysis.

The question states that the enzyme inhibitor slows down the Krebs cycle. This suggests that the inhibitor blocks the rate-determining step of the cycle. Recall that the rate-determining step of Krebs cycle is the isocitrate dehydrogenase step. This converts the six-carbon isocitrate to five-carbon alpha-ketoglutarate. Blocking this step leads to the build up of six-carbon isocitrate and decrease in all of the downstream molecules (including alpha-ketoglutarate).

The first step of Krebs cycle is the formation of a six-carbon molecule from a two-carbon and a four-carbon molecule. The two-carbon molecule acetyl-CoA combines with the four-carbon molecule oxaloacetate to form a six-carbon molecule, citrate. The citrate molecule undergoes a series of reactions in the Krebs cycle that eventually leads to a five-carbon intermediate and, finally, regeneration of the four-carbon oxaloacetate (to be used for the next cycle). The two-carbon molecule, acetyl-CoA, comes from the pyruvate molecule from glycolysis (recall that pyruvate comes from glucose).

The Krebs cycle starts when oxaloacetate combines with acetyl-CoA in order to create citrate. The process is able to work in a cyclic fashion due to the cycle's ability to remake oxaloacetate at the end, so that it can combine with another acetyl-CoA and start the process again.

The Krebs cycle is useful in not only making ATP molecules, but also for creating high-energy electron carriers, such as NADH and FADH2. As a result, the enzyme isocitrate dehydrogenase will be stimulated when these high energy molecules are depleted in the cell. NAD+, or the oxidized form of NADH, stimulates isocitrate dehydrogenase to work more efficiently. All the other options are high-energy molecules, which would slow down the cycle, as enough energy has already been produced.

The Krebs cycle is responsible for creating three molecules of NADH, and one molecule of both ATP and NADH. Acetyl CoA is the 2-carbon molecule that enters the Krebs cycle following pyruvate decarboxylation.

Each of the enzymes is involved in the citric acid cycle except for phosphoglycerate kinase, which is an enzyme that is utilized in glycolysis and gluconeogenesis, and catalyzes the reversible transfer or a phosphate group from 1,3-bisphosphoglycerate to ADP, producing and/or consuming 3-phosphoglycerate and ATP.

Gluconeogenesis is the process in which glucose can be generated from carbon structures that are not the canonical carbohydrate inputs. This is required for many organisms to maintain appropriate blood glucose levels, and for vertebrates gluconeogenesis primarily occurs in the liver, although it has been found to occur in the kidneys as well.

The end product of glycolysis is two molecules of pyruvate, however the molecule used to starts the Krebs cycle is acetyl-CoA. Before going into the Krebs cycle then these 2 pyruvate molecules need to be converted into 2 acetyl-CoA molecules via pyruvate dehydrogenase complex, which occurs in the mitochondria and releases carbon dioxide.

During glycolysis, 2 molecules of NADH are produced per glucose. During the Krebs cycle, 3 molecules of NADH are produced per acetyl-CoA. With 2 molecules of glucose, glycolysis can run twice and produce 4 molecules of acetyl-CoA. Since 2 pyruvates are produced from glucose during glycolysis, a total of 4 are made from our 2 glucose molecules. These 4 pyruvates are then converted to 4 acetyl-CoA molecules. Each of these acteyl-CoA molecules runs through the Krebs cycle yielding a total 12 molecules of NADH. 4 from glycolysis, 12 from the TCA cycle so 16 molecules of NADH total.

Each turn of Krebs cycle produces 3 NADH and 1 ATP. Recall that each turn of Krebs cycle requires a molecule of acetyl-CoA (two-carbon molecule). Acetyl-CoA comes from pyruvate, which in turn comes from glucose. During glycolysis, a molecule of glucose (six-carbon molecule) is converted into two pyruvate molecules; therefore, a molecule of glucose will eventually lead to two acetyl-CoA molecules. This means that there are two turns of Krebs cycle for every glucose molecule and, therefore, for a given molecule of glucose Krebs cycle produces 6 NADH and 2 ATP.

Glycolysis produces a net of 2 ATP and 2 NADH; therefore, Krebs cycle produces three times the NADH and the same amount of ATP as glycolysis.

The question states that the enzyme inhibitor slows down the Krebs cycle. This suggests that the inhibitor blocks the rate-determining step of the cycle. Recall that the rate-determining step of Krebs cycle is the isocitrate dehydrogenase step. This converts the six-carbon isocitrate to five-carbon alpha-ketoglutarate. Blocking this step leads to the build up of six-carbon isocitrate and decrease in all of the downstream molecules (including alpha-ketoglutarate).

The first step of Krebs cycle is the formation of a six-carbon molecule from a two-carbon and a four-carbon molecule. The two-carbon molecule acetyl-CoA combines with the four-carbon molecule oxaloacetate to form a six-carbon molecule, citrate. The citrate molecule undergoes a series of reactions in the Krebs cycle that eventually leads to a five-carbon intermediate and, finally, regeneration of the four-carbon oxaloacetate (to be used for the next cycle). The two-carbon molecule, acetyl-CoA, comes from the pyruvate molecule from glycolysis (recall that pyruvate comes from glucose).

The Krebs cycle starts when oxaloacetate combines with acetyl-CoA in order to create citrate. The process is able to work in a cyclic fashion due to the cycle's ability to remake oxaloacetate at the end, so that it can combine with another acetyl-CoA and start the process again.

The Krebs cycle is useful in not only making ATP molecules, but also for creating high-energy electron carriers, such as NADH and FADH2. As a result, the enzyme isocitrate dehydrogenase will be stimulated when these high energy molecules are depleted in the cell. NAD+, or the oxidized form of NADH, stimulates isocitrate dehydrogenase to work more efficiently. All the other options are high-energy molecules, which would slow down the cycle, as enough energy has already been produced.