| Course | NS230 Macronutrient Metabolism |
|---|---|
| Unit | Unit 4 |
| Paper type | Pathway trace |
| Length | About 1,130 words, 7 pages double-spaced |
| Format | APA 7 student paper |
| School | Purdue University Global |
| Program | BS in Nutrition Science |
| Updated | October 2026 |
Free sample paper for NS230 Unit 4
Two Lactates Back to One Glucose: A Unit 4 Pathway Trace of Gluconeogenesis From Working Muscle to the Liver
[Student Name]
Purdue University Global
NS230: Macronutrient Metabolism
Unit 4 Pathway Trace
[Instructor Name]
[Date]
The trace describes human gluconeogenesis from the sources cited; the exercise scenario is illustrative.
The Setting
A runner finishes a hard 400-meter effort. Her leg muscles have broken down glycogen faster than oxygen could support full oxidation, and lactate has accumulated. Lactate leaves the muscle cells, enters the blood and travels to the liver. There, gluconeogenesis turns two lactate molecules into one glucose, which can return to the blood and to muscle. This loop between muscle and liver is called the Cori cycle (Berg et al., 2019).
Why Gluconeogenesis Is Not Glycolysis in Reverse
Most of glycolysis's ten reactions are near equilibrium and can run in either direction. Three cannot: the steps run by hexokinase, the main phosphofructokinase and pyruvate kinase each release so much energy that reversing them directly is impossible. Gluconeogenesis bypasses each of these with different enzymes, and the bypasses are where the energy cost and the regulation of the pathway lie (Petersen et al., 2017).
The Trace
Each step names its compartment, enzyme, cofactors and energy cost. The trace follows two lactate molecules, which is what one glucose requires.
Step 1. Lactate to pyruvate. Compartment: liver cell cytosol. Enzyme: lactate dehydrogenase. Cofactor: NAD+, reduced to NADH. Cost: none; the step yields 2 NADH for two lactates. These NADH will be needed later in the pathway, which is one reason lactate is a particularly efficient substrate.
Step 2. Pyruvate into the mitochondrion. Pyruvate enters the mitochondrial matrix through the mitochondrial pyruvate carrier.
Step 3. Pyruvate to oxaloacetate. Compartment: mitochondrial matrix. Enzyme: pyruvate carboxylase. Cofactor: biotin, which carries the added carbon dioxide. Cost: 1 ATP per pyruvate, 2 ATP for two. This is the first bypass, around pyruvate kinase. Pyruvate carboxylase is activated by acetyl-CoA, a signal that fatty acid oxidation is supplying energy and that pyruvate can be spared for glucose.
Step 4. Oxaloacetate to phosphoenolpyruvate. Compartment: in liver, phosphoenolpyruvate carboxykinase exists in both the mitochondrion and the cytosol. When lactate is the starting material, the mitochondrial form is used extensively, because the NADH needed later is already present in the cytosol from step 1. Enzyme: phosphoenolpyruvate carboxykinase. Cost: 1 GTP per oxaloacetate, 2 GTP for two. Phosphoenolpyruvate then leaves the mitochondrion. Together, steps 3 and 4 complete the bypass of pyruvate kinase.
Step 5. Phosphoenolpyruvate to 2-phosphoglycerate to 3-phosphoglycerate. Compartment: cytosol. Enzymes: enolase and phosphoglycerate mutase, running in reverse. Cost: none.
Step 6. 3-phosphoglycerate to 1,3-bisphosphoglycerate. Compartment: cytosol. Enzyme: phosphoglycerate kinase, in reverse. Cost: 1 ATP per molecule, 2 ATP for two.
Step 7. 1,3-bisphosphoglycerate to glyceraldehyde-3-phosphate. Compartment: cytosol. Enzyme: glyceraldehyde-3-phosphate dehydrogenase, in reverse. Cofactor: NADH, oxidized to NAD+. Cost: 2 NADH for two molecules, supplied by step 1.
Step 8. Two three-carbon units to fructose-1,6-bisphosphate. One glyceraldehyde-3-phosphate is converted to dihydroxyacetone phosphate by triose phosphate isomerase; aldolase joins it with the other. Compartment: cytosol. Cost: none.
Step 9. Fructose-1,6-bisphosphate to fructose-6-phosphate. Compartment: cytosol. Enzyme: fructose-1,6-bisphosphatase. Cost: none; a phosphate is removed by hydrolysis. This is the second bypass, around phosphofructokinase-1, and the pathway's main control point. It is inhibited by fructose-2,6-bisphosphate, whose levels fall when glucagon is high, so glucagon releases the brake on gluconeogenesis.
Step 10. Fructose-6-phosphate to glucose-6-phosphate. Enzyme: phosphoglucose isomerase. Cost: none.
Step 11. Glucose-6-phosphate to glucose. Compartment: endoplasmic reticulum. Enzyme: glucose-6-phosphatase. Cost: none; hydrolysis again. This third bypass, around hexokinase, exists in liver and kidney but not in muscle, which is why muscle cannot release free glucose to the blood (Petersen et al., 2017).
Every bypass in gluconeogenesis sits exactly where glycolysis cannot run backward, and each is a separate enzyme the cell can regulate, which is how the liver can make glucose and break it down without the two pathways canceling each other out.
Where Glycerol and Alanine Would Change the Bill
The cost depends on the starting material. Alanine, from muscle protein, enters as pyruvate after transamination and pays the same bill as lactate, but it brings no NADH with it, so the cytosolic NADH needed at step 7 must come from elsewhere, usually through the malate route out of the mitochondrion. Glycerol enters at dihydroxyacetone phosphate, above the pyruvate kinase and phosphoglycerate kinase bypasses, so it costs much less: no pyruvate carboxylase, no phosphoenolpyruvate carboxykinase and no phosphoglycerate kinase step. Glycerol is therefore the cheapest gluconeogenic substrate, but adipose tissue supplies only a limited amount of it.
The Energy Bill
For two lactate molecules to one glucose: 2 ATP at pyruvate carboxylase, 2 GTP at phosphoenolpyruvate carboxykinase and 2 ATP at phosphoglycerate kinase, a total of 6 high-energy phosphate bonds. The 2 NADH used at step 7 are supplied by step 1, so they are balanced within the pathway when lactate is the substrate.
The Cost of the Cori Cycle
The muscle gained 2 ATP per glucose converted to lactate by anaerobic glycolysis. The liver spends 6 to turn the lactate back into glucose. Each turn of the cycle therefore costs the body a net 4 high-energy phosphates. The liver pays this cost largely with ATP from fatty acid oxidation, so the cycle effectively shifts the energy burden from working muscle to the liver.
Where the Energy Comes From
During recovery after exercise, and during fasting, the liver oxidizes fatty acids to supply the ATP and GTP that gluconeogenesis needs. The acetyl-CoA produced also activates pyruvate carboxylase, linking fat breakdown to glucose production. In fasting, gluconeogenesis becomes the main source of blood glucose once liver glycogen falls; measurements in fasting humans found it supplied most glucose production within the first day and an even greater share in the second (Rothman et al., 1991).
Why the Liver Does Not Run Both Directions at Once
If glycolysis and gluconeogenesis ran at full speed together in the same cell, the result would be a futile cycle: glucose broken down and rebuilt repeatedly, with nothing gained but heat and a steady loss of ATP. The bypass enzymes prevent this because they are regulated in opposite directions by the same signals. Fructose-2,6-bisphosphate activates phosphofructokinase-1, speeding glycolysis, while inhibiting fructose-1,6-bisphosphatase, slowing gluconeogenesis. When glucagon lowers fructose-2,6-bisphosphate, the balance tips toward making glucose. Acetyl-CoA activates pyruvate carboxylase while inhibiting pyruvate dehydrogenase, steering pyruvate toward glucose rather than oxidation. Some cycling does occur, and may help fine-tune the response, but the paired regulation keeps it small (Petersen et al., 2017).
Other Starting Points
Lactate is one of three main substrates. Alanine from muscle protein enters as pyruvate after transamination; glycerol from fat breakdown enters at dihydroxyacetone phosphate, skipping the first bypass. Each substrate joins the pathway at a different point, and the trace above shows where.
References
Berg, J. M., Tymoczko, J. L., Gatto, G. J., Jr., & Stryer, L. (2019). Biochemistry (9th ed.). W. H. Freeman.
Petersen, M. C., Vatner, D. F., & Shulman, G. I. (2017). Regulation of hepatic glucose metabolism in health and disease. Nature Reviews Endocrinology, 13(10), 572-587. https://doi.org/10.1038/nrendo.2017.80
Rothman, D. L., Magnusson, I., Katz, L. D., Shulman, R. G., & Shulman, G. I. (1991). Quantitation of hepatic glycogenolysis and gluconeogenesis in fasting humans with 13C NMR. Science, 254(5031), 573-576. https://doi.org/10.1126/science.1948033
What the NS230 Unit 4 assignment asks for
The pathway trace asks students to follow one metabolic pathway in full detail. Prompts usually require each step's substrate and product, enzyme, location in the cell, cofactors and energy cost or yield, plus the pathway's regulation and purpose. Choose a starting substrate and say why. Number the steps and keep compartments explicit, since several gluconeogenic steps move between mitochondrion and cytosol. Identify the irreversible steps and their bypasses. Total the energy cost and explain where the energy comes from. Explain how the pathway avoids running against its opposite. Note how other substrates would enter. Cite a biochemistry text and a review. Four to five pages is typical.
Inside the NS230 Unit 4 example
The scenario opens with a runner and the Cori cycle. A section explains why three glycolytic steps need bypasses. Eleven numbered steps follow, each naming compartment, enzyme, cofactor and cost, from lactate dehydrogenase supplying NADH to glucose-6-phosphatase, which muscle lacks. The highlighted sentence explains the logic of the bypasses. An energy bill totals six high-energy phosphates, and a section shows how glycerol and alanine change it. The Cori cycle's net cost of four is calculated, the source of the liver's energy is explained with fasting data, and a section on avoiding futile cycles describes paired regulation. Other starting points close the trace. Each step lists compartment, enzyme, cofactor and cost in the same order.
NS230 Unit 4 rubric: what earns full points
NS230 pathway traces generally reward completeness and accuracy at every step: correct enzymes, compartments, cofactors and energy costs. Points go to correctly identifying the bypasses and explaining why they are needed. A correct energy total, with its sources explained, is scored under accuracy. Regulation, especially how the pathway avoids futile cycling with glycolysis, earns credit for depth. Connecting the pathway to physiology, such as the Cori cycle or fasting, counts under application. Numbered organization and cited sources complete the rubric. Traces that omit compartments, mislabel enzymes or present gluconeogenesis as simple reversal of glycolysis typically lose points. Explaining why muscle cannot release glucose is a common checkpoint in this rubric.
NS230 Unit 4 help from the desk
Gluconeogenesis traces most often go wrong at the first bypass, where students skip the mitochondrial steps or forget that pyruvate carboxylase needs biotin and ATP. Another frequent error is stating that muscle can release glucose, though it lacks glucose-6-phosphatase. Energy totals are often off by counting NADH as an extra cost when lactate supplies it. Compartments are frequently left out. Regulation is sometimes listed without explaining how it prevents futile cycling. If you have chosen a starting substrate and keep losing track of where each step happens, list each enzyme with its compartment before writing a single sentence of the trace. Checking that the NADH used in the trace is supplied by lactate's own oxidation avoids a common double count.
Get an NS230 Unit 4 example written to your instructions
Name the substrate and the condition your Unit 4 prompt specifies, whether lactate after exercise or glycerol during a fast, and send the rubric with it. The trace follows that route line by line, compartments and costs written in, within 24-48h. A first example is prepared without charge. The paper above is an original model document written by our desk, not a submitted student paper and not an official Purdue University Global document.
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NS230 Unit 4 questions, answered
Does the trace have to start from lactate?
No. Prompts vary, and alanine, glycerol and pyruvate are all common starting points. The substrate changes the opening steps: alanine joins after transamination, glycerol enters as dihydroxyacetone phosphate and skips the first bypasses entirely. Whichever substrate your prompt names, the trace should say where it joins and which bypasses it still needs, since that is what graders check first.
Why is gluconeogenesis more than glycolysis reversed?
Because three glycolytic steps release so much energy that they cannot run backward under cellular conditions. The liver goes around each one with a different enzyme, and those detours are also where the two pathways are controlled in opposite directions. A sentence stating that the bypass steps and the control steps are the same steps shows the grader you see the design.
How much of the Cori cycle belongs in the trace?
Enough to explain where the lactate comes from and where the glucose goes: muscle or red blood cells produce lactate, the liver rebuilds glucose, and the glucose returns to the tissues that made the lactate. The energy accounting across the cycle, two ATP gained in muscle against six phosphate bonds spent in liver, is a strong closing sentence if your prompt leaves room.
Where can I find a free NS230 Unit 4 sample paper?
This page presents a complete Unit 4 pathway trace of gluconeogenesis from two lactates to one glucose, with compartments, enzymes, costs, margin notes and APA references.
What does the Cori cycle cost the body?
Muscle gains 2 ATP converting glucose to lactate, while the liver spends 6 high-energy phosphates turning two lactates back into glucose, so each turn costs a net 4, paid mostly by fatty acid oxidation in the liver.