Chapter Summary, Questions Answers - The Feed-Fast Cycle

CHAPTER SUMMARY

The flow of intermediates through metabolic pathways is controlled by four mechanisms: 1) the availability of substrates, 2) allosteric activation and inhibition of enzymes, 3) covalent modification of enzymes, and 4) induction-repression of enzyme synthesis. In the absorptive state, the 2–4-hour period after ingestion of a meal, these regulatory mechanisms ensure that available nutrients are captured as glycogen, triacylglycerol (TAG), and protein (Figure 24.20). During this interval, transient increases in plasma glucose, amino acids, and TAG occur, the last primarily as components of chylomicrons synthesized by the intestinal mucosal cells. The pancreas responds to the elevated levels of glucose with an increased secretion of insulin and a decreased secretion of glucagon by the pancreas. The elevated insulin-to-glucagon ratio and the ready availability of circulating substrates make the absorptive state an anabolic period during which virtually all tissues use glucose as a fuel. In addition, the liver replenishes its glycogen stores, replaces any needed hepatic proteins, and increases TAG synthesis. The latter are packaged in very-low-density lipoproteins, which are exported to the peripheral tissues. Adipose tissue increases TAG synthesis and storage, whereas muscle increases protein synthesis to replace protein degraded since the previous meal. In the fed state, the brain uses glucose exclusively as a fuel. In the absence of food, plasma levels of glucose, amino acids, and TAG fall, triggering a decline in insulin secretion and an increase in glucagon and epinephrine release. The decreased insulin/counterregulatory hormone ratio and the decreased availability of circulating substrates make the fasting state a catabolic period. This sets into motion an exchange of substrates among liver, adipose tissue, skeletal muscle, and brain that is guided by two priorities: 1) the need to maintain adequate plasma levels of glucose to sustain energy metabolism of the brain and other glucose-requiring tissues and 2) the need to mobilize fatty acids (FAs) from adipose tissue and release ketone bodies from liver to supply energy to other tissues. To accomplish these goals, the liver degrades glycogen and initiates gluconeogenesis, using increased fatty acid oxidation as a source of the energy and reducing equivalents needed for gluconeogenesis and to supply the acetyl coenzyme A building blocks for ketogenesis. The adipose tissue degrades stored TAG, thus providing FAs and glycerol to the liver. The muscle can also use FAs as fuel as well as ketone bodies supplied by the liver. Muscle protein is degraded to supply amino acids for the liver to use in gluconeogenesis, but deceases as ketone bodies increase. The brain can use both glucose and ketone bodies as fuels. From late fasting into starvation, the kidneys play important roles b y synthesizing glucose and excreting the protons from ketone body dissociation as ammonium (NH₄⁺).

Figure 24.19 Intertissue relationships during starvation and the hormonal signals that promote them. P = phosphate; TCA = tricarboxylic acid; CoA = coenzyme A.

Figure 24.20 Key concept map for feed-fast cycle. VLDL = very-low-density lipoprotein.

Study Questions
Choose the ONE best answer.

24.1 Which one of the following is elevated in plasma during the absorptive (fed) period as compared with the postabsorptive (fasted) state?

A. Acetoacetate

B. Chylomicrons

C. Free fatty acids

D. Glucagon

Correct answer = B. Triacylglycerol-rich chylomicrons are synthesized in (and released from) the intestine following ingestion of a meal. Acetoacetate, free fatty acids, and glucagon are elevated in the fasted state, not the absorptive state.

24.2 Which one of the following statements concerning liver in the fed state is correct?

A. Fructose 2,6-bisphosphate is elevated.

B. Insulin stimulates the uptake of glucose.

C. Most enzymes that are regulated by covalent modification are in the phosphorylated state.

D. The oxidation of acetyl coenzyme A is increased.

E. The synthesis of glucokinase is repressed.

Correct answer = A. The increased insulin and decreased glucagon levels characteristic of the fed state promote the synthesis of fructose 2,6-bisphosphate, which allosterically activates phosphofructokinase-1 of glycolysis. Most covalently modified enzymes are in the dephosphorylated state and are active. Acetyl coenzyme A is not oxidized in the fed state because it is being used in fatty acid synthesis. Uptake of glucose (by glucose transporter-2) into the liver is insulin independent. Synthesis of glucokinase is induced by insulin in the fed state.

24.3 Which one of the following enzymes is phosphorylated and active in an individual who has been fasting for 12 hours?

A. Arginase

B. Carnitine palmitoyltransferase-1

C. Fatty acid synthase

D. Glycogen synthase

E. Hormone-sensitive lipase

F. Phosphofructokinase-1

G. Pyruvate dehydrogenase

Correct answer = E. Hormone-sensitive lipase of adipocytes is phosphorylated and activated by protein kinase A in response to epinephrine. Choices A, B, C, and F are not regulated covalently. Choices D and G are regulated covalently but are inactive if phosphorylated.

24.4 For a 70-kg man, in which one of the periods listed below do ketone bodies supply the major portion of the caloric needs of brain?

A. Absorptive period

B. Overnight fast

C. Three-day fast

D. Four-week fast

E. Five-month fast

Correct answer = D. Ketone bodies, made from the acetyl coenzyme A product of fatty acid oxidation, increase in the blood in fasting but must reach a critical level to cross the blood–brain barrier. Typically this occurs in the second to third week of a fast. Fat stores in a 70-kg man would not be able to supply his energy needs for 5 months.

24.5 The diagram below shows inputs to and outputs from pyruvate, a central molecule in energy metabolism.

Which letter on the diagram represents a reaction that requires biotin and is activated by acetyl coenzyme A?

Correct answer = C. Pyruvate carboxylase, a mitochondrial enzyme of gluconeogenesis, requires biotin (and adenosine triphosphate) and is allosterically activated by acetyl coenzyme A from fatty acid oxidation. None of the other choices meets these criteria.