Chapter 24
Integration of Metabolism: Cellular Signaling
1
SUMMARY
Section 24.1
All metabolic pathways are related, and some metabolites appear in several
pathways.
Section 24.2
The sources of substrates for catabolism and for anabolism are the nutrients
derived from foodstuffs.
In humans, the choice of diet becomes important in the interest of obtaining
Section 24.3
Sophisticated fine tuning of metabolic processes in multicellular organisms is
possible through the actions of hormones and second messengers.
In humans, a complex hormonal system has evolved that requires releasing
factors (under the control of the hypothalamus), trophic hormones (under the
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Section 24.4
When a hormone binds to its receptor on the plasma membrane of a target cell, it
sets off a cascade of reactions by which second messengers elicit the actual
cellular response.
Two of the most important second messengers, cyclic AMP (cAMP) and
phosphatidylinositol- 4,5-bisphosphate (PIP2), activate protein kinases, which
gluconeogenesis in the liver, leading to increased glucose production.
Hormonal triggering can be added to other levels of control of metabolism, such
as allosteric activation and covalent modification, to ensure an efficient response
to the needs of the organism.
Section 24.5
Insulin’s primary job is to stimulate the glucose transporters in muscle —
particularly the GLUT4 transporter—to take up glucose from the blood.
In addition, it has a wide range of intracellular effects, such as switching off
LECTURE NOTES
The intent of this chapter is to tie together what students have already learned
about metabolism by seeing how these concepts apply to nutrition, and hormonal
control in a large-scale organism. The material in this chapter will take two to three
lectures to cover.
Integration of Metabolism: Cellular Signaling 3
LECTURE OUTLINE
I. Connections among metabolic pathways
II. Biochemistry and nutrition
A. Required nutrients
1. Macronutrients
III. Hormones and second messengers
A. Hormones
B. Second messengers
IV. Hormonal control in metabolism
V. Insulin
A. Structure
B. Receptors
ANSWERS TO PROBLEMS
24.1 Connections between Metabolic Pathways
1. ATP and NADPH are the two molecules that link the most pathways.
3.
(a) Fructose-6-phosphate—from the pentose phosphate pathway (PPP).
(b) Oxaloacetate—to phosphoenolpyruvate in gluconeogenesis, to and from
aspartate, to the glyoxylate cycle via citrate.
(c) Glucose-6-phosphate—to PPP, to and from glycogen in animals, to starch in
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(k) Phosphoenolpyruvate—from oxaloacetate in gluconeogenesis.
(l) Citrate—to the glyoxylate cycle, transport across the mitochondrial membrane for
5.
(a) High ATP or NADH concentration and the citric acid cycle: isocitrate
dehydrogenase (and the citric acid cycle) would be inhibited. The resulting pileup
of acetyl-CoA (or citrate) would stimulate fatty acid and steroid synthesis,
gluconeogenesis, and (in plants and some microorganisms) the glyoxylate cycle.
(b) High ATP concentration and glycolysis: phosphofructokinase-1 (and glycolysis)
6. Many compounds, such as oxaloacetate, pyruvate, and acetyl-CoA, play a role in
a number of reactions. More to the point, the end products of some pathways are
the starting points of others. Each pathway is one aspect of an overall metabolic
scheme.
7. The effect of biochemical pathways can be reversed. Examples include
glycolysis and gluconeogenesis, glycogen formation and synthesis, and the
8. Transport processes are especially important for substances, such as
oxaloacetate, that cannot cross the mitochondrial membrane. The same is true
for electrons. Shuttle mechanisms must exist to transport electrons as the
reduced form of important compounds. Compounds that cannot cross the
membrane must be converted to ones that can, and then must be converted
Integration of Metabolism: Cellular Signaling 5
24.2 Biochemistry and Nutrition
11. The old pyramid assumed that all carbohydrates and fats were the same and that
carbohydrates were good and all fats were bad. The new pyramid recognizes
12. Fats and carbohydrates can be stored when they are consumed in excess. Fats
are stored as triacylglycerols and carbohydrates are stored as glycogen.
However, proteins consumed in excess are not stored. The extra protein is
broken down. The amino groups are released as urea and the carbon skeletons
are stored as carbohydrate or fat.
13. Saturated fatty acids have been correlated with increased levels of LDL, which
16. Carbohydrates are the main energy source. Excess fat consumption can lead to
the formation of ―ketone bodies‖ and to atherosclerosis. Diets extremely high in
protein can put a strain on the kidneys.
17. The liver is the primary organ for alcohol metabolism and for disposing of drugs
(legal, illegal, and accidental) and halocarbon compounds. When the liver spends
19. Low levels of iodine in the diet often lead to hypothyroidism and an enlarged
thyroid gland (goiter). This condition has largely been eliminated by the addition
of sodium iodide to commercial table salt.
20. Lucullus breaks down the protein in the tuna to amino acids, which in turn
undergo the urea cycle and the breakdown of the carbon skeleton described in
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23. After a person is fully grown, many amino acids are scavenged and recycled by
the body. Because all proteins contain at least some of these two amino acids,
24. The early colonists always cooked in iron pots; enough iron is leached out to
25. Diets high in fiber are usually lower in fats, especially saturated fats; fiber
adsorbs many potentially toxic substances, such as cholesterol and halocarbons,
preventing their absorption into the body; fiber decreases transit time through the
intestine, so any toxic materials in food remain in the body for less time and have
a smaller chance of being absorbed or otherwise causing problems.
26. This claim has a chemical basis. Calcium carbonate dissolves in stomach acid,
releasing calcium ion in its usual hydrated form. Calcium citrate is likely to have
27. Alcohol provides calories but does not provide vitamins. This is one of the
28. Metal ions play a role in the structure and function of proteins and some
coenzymes. They tend to do so because they operate as Lewis acids.
29. Severe depletion of glycogen often results in a rebound effect, in which so much
is made that some is stored in inappropriate tissues, including the heart, and
mineral imbalances often occur. It is best to exercise moderately before the
24.3 Hormones and Second Messengers
31. Hormones can have several different kinds of chemical structures, including
steroids, polypeptides, and amino acid derivatives.
32. The anterior pituitary stimulates release of trophic hormones, which in turn
stimulate specific endocrine glands; the workings of the adrenal cortex, the
thyroid, and the gonads can all be affected as a result. The adrenal cortex
Integration of Metabolism: Cellular Signaling 7
disease, characterized by hypoglycemia, weakness, and increased susceptibility
to stress. The opposite condition, hyperadrenocorticism, is Cushing’s syndrome.
33. The hypothalamus secretes hormone-releasing factors. Under the influence of
34. Thyroxine is an amino acid derivative and is absorbed directly from the gut into
the bloodstream. If insulin were taken orally, it would be hydrolyzed to amino
acids in the stomach and intestine.
35. G proteins get their name because they bind GTP as part of their effect. An
example is the G protein that is linked to the epinephrine receptor and leads to
37. Human growth hormone is a peptide hormone. If it were taken orally, the peptide
would be degraded to its component amino acids in the small intestine and would
be rendered useless.
24.4 Hormones and the Control of Metabolism
38. Epinephrine and glucagon are the two that were discussed the most in this book.
41. The G protein is bound to GTP. Eventually, the GTP is hydrolyzed to GDP, which
causes it to dissociate from adenylate cyclase. This stops the hormone response
until the hormone dissociates from the receptor, the G protein trimers are
rejoined, and the process starts over again.
42. IP3 is a polar compound and can dissolve in the aqueous environment of the
cytosol; DAG is nonpolar and interacts with the side chains of the membrane
phospholipids.
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46. In cholera, adenylate cyclase is permanently ―turned on.‖ This in turn stimulates
active transport of Na+ and water from epithelial cells, leading to diarrhea.
47.
(a) Stoichiometric amounts of cAMP are required to activate cAMP-dependent
protein kinase.
48. A phosphatase dephosphorylates glycogen phosphorylase and glycogen
synthetase, inactivating and activating them, respectively. The phosphatase
becomes active in response to high concentrations of glucose.
49. Low-carbohydrate diets are designed to prevent the high blood sugar levels that
24.5 Insulin and Its Effects
50. Insulin’s primary function is to stimulate the transport of glucose out of the blood
and into the cell.
51. The second messenger is a protein called the insulin receptor substrate, which is
phosphorylated on a tyrosine by the insulin receptor kinase.
52. When insulin binds to its receptor, the -subunit of the receptor kinase
Integration of Metabolism: Cellular Signaling 9
54. Insulin and epinephrine normally have opposite effects, but they both stimulate
muscle glycolysis. Epinephrine is the hormone that signals the need for quick
energy, which means the muscle cells must be able to use glucose via glycolysis.
55. Prerace diet can be critical to a runner. If the race is at 9 AM, and the runner gets
up at 7 AM and then eats a typical American breakfast of cereal, toast, or
56. It has been shown that the GLUT4 transporter responds to physical activity.
57. GLUT4 is one of the glucose transporters on muscle cells. It responds to insulin
by moving glucose out of the blood and into the cell. In type II diabetes, insulin is
58. Adipocytes, liver cells, and muscle cells.
59. Obese and diabetic individuals have a much higher risk of getting cancer than
lean, healthy people, and when they do get cancer, their risk of dying from it is
greater
60. The Warburg effect describes a situation where, when bathed in large amounts
of glucose, and with significant insulin to allow the glucose to enter the cells,
61. Because of the link between some cancers, obesity, and diabetes, one can think
of cancer as being a lifestyle disease as people that stay lean, fit, and healthy are
therefore less likely to get cancer.