MCAT practice · Biological and Biochemical Foundations · 1D Bioenergetics and metabolism
Blood fuels and hormones over five days of fasting
An original practice passage written for this site, not an AAMC item. Exam pace is about 8 minutes for a passage like this.
Between meals, the body must hold plasma glucose within a narrow range. Red blood cells depend on glucose entirely, and in a person eating a normal diet the brain consumes most of the glucose the liver releases. As a fast lengthens from hours to days, both the source of blood glucose and the fuels burned by other tissues change. To chart this transition, investigators studied eight healthy adult volunteers who ate a standard mixed meal and then consumed only water and electrolytes for 5 days.
Venous blood was sampled 4, 12, 24, 48, 72, and 120 h after the meal. Plasma glucose, free fatty acids (FFA), and β-hydroxybutyrate, the main circulating ketone body, were measured enzymatically (Figure 1). Plasma insulin and glucagon were measured by immunoassay, and total nitrogen, most of it as urea, was measured in each 24-h urine collection (Table 1). Because the subjects ate no protein, urinary nitrogen was used as an index of the breakdown of body protein.
Plasma glucose declined gradually but stayed above 3.5 mM throughout. FFA rose about fourfold over the fast. β-Hydroxybutyrate changed little during the first 12 h and then climbed steeply, reaching a concentration well above that of FFA by the end of the study. Insulin fell and glucagon rose, so the insulin-to-glucagon ratio declined steadily. Urinary nitrogen excretion peaked during the second day and then fell, even though plasma glucose remained nearly constant after 72 h.
The investigators noted that nitrogen excretion on the fifth day implied a much smaller daily loss of body protein than would be needed if amino acids were supplying all of the carbon for the glucose their tissues were using. They proposed that the decline in protein breakdown after the second day was a consequence of the rise in circulating ketone bodies, and they planned a follow-up study to test that idea directly.
- Glucose
- FFA
- BHB
| Time since last meal (h) | Insulin (µU/mL) | Glucagon (pg/mL) | Urinary nitrogen (g/day) |
|---|---|---|---|
| 24 | 7 | 100 | 9.5 |
| 48 | 5 | 120 | 11 |
| 72 | 4 | 135 | 10 |
| 120 | 3.5 | 140 | 7.5 |
Data are illustrative, constructed for practice.
1. According to Figure 1, plasma β-hydroxybutyrate increased by approximately what factor between 24 h and 72 h of the fast?
- A. Wrong: about 2-fold is the rise from 48 h (1.20 mM) to 72 h (2.20 mM), which starts the interval at the wrong time point.
- B. Wrong: 4-fold is the rise from 24 h (0.30 mM) to 48 h (1.20 mM), which stops the interval a day too early.
- C. Right: β-hydroxybutyrate went from 0.30 mM at 24 h to 2.20 mM at 72 h, and 2.20 / 0.30 is about 7.3.
- D. Wrong: about 11-fold is the rise from 24 h to 120 h (3.40 / 0.30), which reads the last time point instead of 72 h.
2. The fall in the insulin-to-glucagon ratio shown in Table 1 increases hepatic ketone production. Which change in the liver most directly links this hormonal shift to faster fatty acid oxidation?
- A. Wrong: this reverses both links. In the fasted state acetyl-CoA carboxylase is phosphorylated and inhibited, and malonyl-CoA inhibits CPT-I rather than opening it.
- B. Wrong: in the fasted liver, PKA phosphorylates and inhibits pyruvate kinase so that PEP is kept for gluconeogenesis; the acetyl-CoA for ketogenesis comes from fatty acids.
- C. Right: with low insulin and high glucagon, acetyl-CoA carboxylase is phosphorylated and inhibited, malonyl-CoA falls, CPT-I is released from inhibition, and more fatty acyl groups enter mitochondria for β-oxidation and ketogenesis.
- D. Wrong: the liver lacks SCOT (thiophorase) and does not burn its own ketone bodies; even if it did, that would lower, not raise, ketone output.
3. Which follow-up study would best test the investigators' proposal that rising ketone bodies cause the decline in protein breakdown?
- A. Right: this manipulates the proposed cause (ketone level) at a time when ketones are still low, holds the main competing variables (glucose and insulin) constant, and includes a saline control, so a difference in urinary nitrogen can be attributed to the ketones.
- B. Wrong: without a control group, any change could reflect the ongoing day-to-day decline in nitrogen excretion seen in Table 1 rather than the infusion.
- C. Wrong: a larger correlational study would only repeat the observation that the two variables change together over time; it cannot separate ketones from other things that also change with fasting duration.
- D. Wrong: glucose infusion raises insulin, which suppresses lipolysis and ketogenesis and also affects protein turnover directly, so any change in nitrogen could not be assigned to ketones.
4. Between 72 h and 120 h, urinary nitrogen fell while plasma glucose stayed nearly constant. Which explanation best accounts for both observations?
- A. Right: as β-hydroxybutyrate climbed (Figure 1), the brain shifted onto ketone bodies and needed less glucose, so the liver needed fewer amino acids from muscle protein, and nitrogen excretion fell while glucose held steady.
- B. Wrong: the brain has little capacity to oxidize long-chain fatty acids, so rising FFA cannot be what reduced its glucose demand.
- C. Wrong: even-chain fatty acids cannot yield net glucose in mammals, because the citric acid cycle releases two carbons as CO₂ for each acetyl-CoA that enters, so no oxaloacetate is gained.
- D. Wrong: muscle lacks glucose-6-phosphatase and cannot release free glucose.
5. A child with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency undergoes a supervised fast. At 24–48 h, compared with the volunteers in Figure 1, the child's plasma would most likely show which pattern?
- A. Wrong: ketone bodies are built from the acetyl-CoA that β-oxidation produces; a stalled pathway cannot supply it, so ketones are low, not high.
- B. Right: lipolysis is intact, so FFA are released and accumulate, but β-oxidation stalls at medium chains, so the liver makes little acetyl-CoA for ketogenesis and lacks the ATP and acetyl-CoA signal that drive gluconeogenesis; tissues also lean harder on glucose. The result is hypoketotic hypoglycemia.
- C. Wrong: blocking fat oxidation does not spare glucose; it removes the liver's energy for gluconeogenesis and forces tissues to use more glucose, so glucose falls.
- D. Wrong: the defect is in mitochondrial oxidation, not in adipose lipolysis, which glucagon and low insulin still drive, so FFA rise rather than fall.
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