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.pdfdegraded in reactions that
form high-energy phosphorylated intermediates of the pathway (Fig. 20.11). These activated high-energy
intermediates provide the energy for the generation of ATP from ADP without involving electron transfer
to O2. Therefore, this pathway is called anaerobic glycolysis, and ATP is generated from substrate-level
phosphorylation rather than from oxidative phosphorylation (see Chapter 24). Anaerobic glycolysis is a
critical source of ATP for cells that have a decreased O2 supply either because they are physiologically
designed that way (e.g., cells in the kidney medulla, rapidly working muscle, red blood cells) or because
their supply of O2 has been pathologically decreased (e.g., coronary artery disease).
VI. Oxygenases and Oxidases Not Involved in ATP Generation
Approximately 90% to 95% of the O2 we consume is used by the terminal oxidase in the ETC for ATP
generation via oxidative phosphorylation. The remainder of the O2 is used directly by oxygenases and
other oxidases, enzymes that oxidize a compound in the body by transferring electrons directly to O2 (Fig.
20.12). The large positive reduction potential of O2 makes all of these reactions extremely favorable
thermodynamically, but the electronic structure of O2 slows the speed of electron transfer. These enzymes,
therefore, contain a metal ion that facilitates reduction of O2.A. Oxidases Oxidases transfer electrons from the substrate to O2, which is reduced to water (H2O) or to hydrogen
peroxide (H2O2). The terminal protein complex in the ETC, called cytochrome oxidase, is an oxidase
because it accepts electrons donated to the chain by NADH and FAD(2H) and uses these to reduce O2 to
H2O. Most of the other oxidases in the cell form H2O2 instead of H2O and are called peroxidases.
Peroxidases are generally confined to peroxisomes to protect DNA and other cellular components from
toxic free radicals (compounds containing single electrons in an outer orbital) generated by H2O2.
B. Oxygenases
Oxygenases, in contrast to oxidases, incorporate one or both of the atoms of oxygen into the organic
substrate (see Fig. 20.12). Monooxygenases, enzymes that incorporate one atom of oxygen into the
substrate and the other into H2O, are often named hydroxylases (e.g., phenylalanine hydroxylase, which
adds a hydroxyl group to phenylalanine to form tyrosine) or mixed-function oxidases. Monooxygenases
require an electron-donor substrate, such as NADPH; a coenzyme such as FAD, which can transfer single
electrons; and a metal or similar compound that can form a reactive oxygen complex. They are usually
found in the endoplasmic reticulum and occasionally in mitochondria. Dioxygenases, enzymes that
incorporate both atoms of oxygen into the substrate, are used in the pathways for converting arachidonate
into prostaglandins, thromboxanes, and leukotrienes. VII. Energy Balance
Our total energy expenditure is equivalent to our O2 consumption (Fig. 20.13). The resting metabolic rate
(energy expenditure of a person at rest, at 25°C, after an overnight fast) accounts for approximately 60%
to 70% of our total energy expenditure and O2 consumption, and physical exercise accounts for the
remainder. Of the resting metabolic rate, approximately 90% to 95% of O2 consumption
is used by the
mitochondrial ETC, and only 5% to 10% is required for nonmitochondrial oxidases and oxygenases and
is not related to ATP synthesis. Approximately 20% to 30% of the energy from this mitochondrial O2consumption is lost by proton leak back across the mitochondrial membrane, which dissipates the
electrochemical gradient without ATP synthesis. The remainder of our O2 consumption is used for
ATPases that maintain ion gradients and for biosynthetic pathways.
ATP homeostasis refers to the ability of our cells to maintain constant levels of ATP despite
fluctuations in the rate of use. Thus, increased use of ATP for exercise or biosynthetic reactions increases
the rate of fuel oxidation. The major mechanism used is feedback regulation; all of the pathways of fuel
oxidation that lead to generation of ATP are feedback-regulated by ATP levels or by compounds related to
the concentration of ATP. In general, the less ATP is used, the less fuel will be oxidized to generate ATP.
According to the first law of thermodynamics, the energy (in calories) in our consumed fuel can never
be lost. Consumed fuel is either oxidized to meet the energy demands of the BMR plus exercise, or it is
stored as fat. Thus, an intake of calories in excess of those expended results in weight gain. The simple
statement, “If you eat too much and don’t exercise, you will gain weight,” is really a summary of the
bioenergetics of the ATP–ADP cycle. CLINICAL COM M ENTS
Otto S. Otto S. visited his physician, who noted the increased weight. The physician recommended
several diet modifications to Otto that would decrease the caloric content of his diet and pointed
out the importance of exercise for weight reduction. He reminded Otto that the American Heart
Association recommends at least 30 minutes of moderate-intensity aerobic activity at least 5 days per
week or at least 25 minutes of vigorous aerobic activity at least 3 days per week. He also reminded Otto
that he would want to be a role model for his patients. Otto decided to begin an exercise regimen that
included at least 30 minutes of running and tennis at least 5 days a week. Stanley T. Mr. T. exhibited the classical signs and symptoms of hyperthyroidism (increased
secretion of the thyroid hormones T3 and T4; see Fig. 11.8 for the structure of T3), including a goiter
(enlarged thyroid gland). T3 is the more active form of the hormone. T4 is synthesized and secreted in
approximately 10 times greater amounts than T3. Liver and other cells contain an enzyme (a deiodinase)that removes one of the iodines from T4, converting it to T3. Thyroid function tests confirmed this
diagnosis.
Thyroid hormones (principally T3) modulate cellular energy production and use through their ability
to increase gene transcription (see Fig. 16.13) of many proteins involved in intermediary metabolism,
including enzymes in the TCA cycle and oxidative phosphorylation. They increase the rate of ATP use by
the Na+,K+-ATPase and other enzymes. They also affect the efficiency of energy transformations, so that
either more fuel must be oxidized to maintain a given level of ATP or more ATP must be expended to
achieve the desired physiologic response. The loss of weight experienced by Stanley T., in spite of a
very good appetite, reflects his increased caloric requirements and less efficient
use of fuels. The result is
enhanced oxidation of adipose tissue stores as well as a catabolic effect on muscle and other proteincontaining tissues. Through mechanisms that are not well understood, increased levels of thyroid hormone
in the blood also increase the activity or “tone” of the sympathetic (adrenergic) nervous system. An
activated sympathetic nervous system leads to a more rapid and forceful heartbeat (tachycardia and
palpitations), increased nervousness (anxiety and insomnia), tremulousness (a sense of shakiness or
jitteriness), and other symptoms.
Cora N. Cora N. was in left ventricular heart failure (LVF) when she presented to the hospital with
her second heart attack in 8 months. The diagnosis of LVF was suspected, in part, by her rapid heart
rate (104 beats/minute) and respiratory rate. On examining her lungs, her physician heard respiratory
rales (or crackles) caused by inspired air bubbling in fluid that had filled her lung air spaces secondary to
LVF. This condition is referred to as congestive heart failure.
Congestive heart failure occurs when the weakened pumping action of the left ventricular
heart muscle, often from ischemia, leads to a reduced blood flow from the heart to the rest
of the body. This leads to an increase in blood volume in the vessels that bring oxygenated blood
from the lungs to the left side of the heart. The pressure inside these pulmonary vessels eventually
reaches a critical level, above which water from the blood moves down a “pressure gradient”
from the capillary lumen into alveolar air spaces of the lung (transudation). The patient
experiences shortness of breath as the fluid in the air spaces interferes with oxygen exchange from
the inspired air into arterial blood, causing hypoxia. The hypoxia then stimulates the respiratory
center in the central nervous system, leading to a more rapid respiratory rate in an effort to
increase the oxygen content of the blood. As the patient inhales deeply, the physician hears
gurgling/crackling sounds (known as inspiratory rales) with a stethoscope placed over the
posterior lung bases. These sounds represent the bubbling of inspired air as it enters the fluidfilled pulmonary alveolar air spaces.
Cora’s rapid heart rate (tachycardia) resulted from a reduced capacity of her ischemic, failing left
ventricular muscle to eject a normal amount of blood into the arteries leading away from the heart with
each contraction. The resultant drop in intra-arterial pressure signaled a reflex response in the central
nervous system that, in turn, caused an increase in heart rate in an attempt to bring the total amount of
blood leaving the left ventricle each minute (the cardiac output) back toward a more appropriate level tomaintain systemic blood pressure.
Initial treatment of Cora’s congestive heart failure will include efforts to reduce the workload of the
heart by decreasing blood volume (preload) with diuretics and decreasing her blood pressure, and the
administration of oxygen by nasal cannula to increase the oxygen levels in her blood.
BIOCHEM ICAL COM M ENTS
Active Transport and Cell Death. Most of us cannot remember when we first learned that we
would die if we stopped breathing. But exactly how cells die from a lack of oxygen is an intriguing
question. Hypoxia leads to both physical and transcriptional changes. Pathologists generally describe two
histologically distinct types of cell death: necrosis and apoptosis (programmed cell death). Cell death
from a lack of O2, such as occurs during an MI, can be very rapid and is considered necrosis. The lack of
ATP for the active transport of Na+ and Ca2+ triggers some of the death cascades that lead to necrosis
(Fig. 20.14).
The influx of Na+ and loss of the Na+ gradient across the plasma membrane is an early event
accompanying ATP depletion during interruption of the O2 supply. One consequence of the increased
intracellular Na+ concentration is that other transport processes driven by the Na+ gradient are impaired.
For example, the Na+/H+ exchanger, which normally pumps out H+ generated from metabolism in
exchange for extracellular Na+, can no longer function, and intracellular pH may drop. The increased
intracellular H+ may impair ATP generation from anaerobic glycolysis. As a consequence of increased
intracellular ion concentrations, H2O enters the cells and hydropic swelling occurs. Swelling isaccompanied by the release of creatine kinase MB subunits, troponin I, and troponin C into the blood.
Some of these enzymes are measured in the blood to help diagnose an MI (see Chapters 6 and 7).
Swelling is an early event and is considered a reversible stage of cell injury. Normally, intracellular Ca2+ concentration is carefully regulated to fluctuate at low levels
(intracellular Ca2+ concentration is <10−7 M, compared to ~10−3 M in extracellular fluid). Fluctuations
of Ca2+ concentration at these low levels regulate myofibrillar contraction, energy metabolism, and other
cellular processes. However, when Ca2+ concentration is increased above this normal range, it triggers
cell death (necrosis). High Ca2+ concentrations activate a phospholipase that increases membrane
permeability, resulting in further loss of ion gradients across the cell membrane. They also trigger opening
of the mitochondrial permeability transition pore, which results in loss of mitochondrial function and
further impairs oxidative phosphorylation.
Intracellular Ca2+ levels may increase as a result of cell swelling, the lack of ATP for ATP-dependent
Ca2+ pumps, or the loss of the Na+ gradient. Normally, Ca2+-ATPases located in the plasma membrane
pump Ca2+ out of the cell. Ca2+-ATPases in the endoplasmic reticulum, and in the sarcoplasmic reticulum
of heart and other muscles, sequester Ca2+ within the membranes, where it is bound by a low-affinity
binding protein. Ca2+ is released from the sarcoplasmic reticulum in response to a nerve impulse, which
signals contraction, and the increase of Ca2+ stimulates both muscle contraction and the oxidation of fuels.
Within the heart, another Ca2+ transporter protein, the Na+/Ca2+ exchange transporter, coordinates the
efflux of Ca2+ in exchange for Na+, so that Ca2+ is extruded with each contraction. Hypoxia also induces the transcription of genes in an attempt to compensate for the hypoxic
conditions. A family of transcription factors, known as hypoxia-inducible factors (HIFs), are activated
under hypoxic conditions. These factors bind to hypoxia-responsive elements (promoter-proximal
elements) in the regulatory region of target genes. More than 70 target genes are regulated by HIFs,
including the gene for erythropoietin, which stimulates increased red blood cell production. Induction of
these genes allows cells to adapt to and survive for some time under these hypoxic conditions.
KEY CONCEPTS
Bioenergetics refers to cellular energy transformations.
The high-energy phosphate bonds of ATP are a cell’s primary source of energy. ATP is generated through cellular respiration, the oxidation of fuels to carbon dioxide and water.
ATP can also be generated, at reduced levels, via anaerobic glycolysis (in the absence of O2).
The electrons captured from fuel oxidation generate NADH and FAD(2H), which are used to
regenerate ATP via the process of oxidative phosphorylation.
The energy available from ATP hydrolysis can be used for the following: Mechanical work (muscle contraction)
Transport work (establishment of ion gradients across membranes)
Biochemical work (energy-requiring chemical reactions, including detoxification reactions)
Energy released from fuel oxidation that is not used for work is transformed into and released as
heat.
The many pathways of fuel oxidation are coordinately regulated to maintain ATP homeostasis.ΔG0′ is the change in Gibbs free energy at pH 7.0 under standard conditions between the substrates
and products of a reaction.
Fuel oxidation has a negative ΔG0;′ the products formed have less chemical energy than the reactants
(an exergonic reaction pathway).
ATP synthesis has a positive ΔG0′ and is endergonic; the reaction requires energy. Metabolic pathways have an overall negative ΔG0,′ which is obtained by summing all of the ΔG0′
values for each reaction in the pathway.
Oxidation–reduction reactions can be related to changes in free energy, the use of E0,′ the chemical’s
affinity for electrons. Compounds with higher E0′ values have greater affinity for electrons than
those with lower E0′ values.
Diseases discussed in this chapter are summarized in Table 20.5. REVIEW QUESTIONS—CHAPTER 20
1.ATP is the cells’ major chemical form of energy, and often it is converted to ADP during reactions,
thereby releasing energy to allow the reaction to proceed in the forward direction. The highest
energy phosphate bond in ATP is located between which of the following groups? A. Adenosine and phosphate
B. Ribose and phosphate C. Ribose and adenine
D. Two hydroxyl groups in the ribose ring E. Two phosphate groups
2.All cells require energy to survive, and the laws of thermodynamics need to be followed within
biologic systems. Which one of the following bioenergetic terms or phrases is defined correctly?
A. The first law of thermodynamics states that the universe tends toward a state of increased order.
B. The second law of thermodynamics states that the total energy of a system remains constant.
C. The change in enthalpy of a reaction is a measure of the total amount of heat that can be released
from changes in the chemical bonds.D. ΔG0′ of a reaction is the standard free-energy change measured at 37°C and a pH of 7.4.
E. A high-energy bond is a bond that releases >3 kcal/mol of heat when it is hydrolyzed.
3.In order for a cell to carry out its biologic functions, the intracellular
reactions need to be directed to
follow a certain pathway. Which one statement best describes the direction a chemical reaction will
follow?
A.A reaction with positive free energy will proceed in the forward direction if the substrate
concentration is raised high enough.
B.Under standard conditions, a reaction will proceed in the forward direction if the free energy
ΔG0′ is positive.
C.The direction of a reaction is independent of the initial substrate and product concentrations
because the direction is determined by the change in free energy.
D.The concentration of all of the substrates must be higher than that of all of the products for the
reaction to proceed in the forward direction.
E.The enzyme for the reaction must be working at >50% of its maximum efficiency for the reaction
to proceed in the forward direction.
4. A patient, Mr. P., has just suffered a heart attack. As a consequence, his heart will display which one
of the following changes?
A.Increased intracellular O2 concentration
B.Increased intracellular ATP concentration
C.Increased intracellular H+ concentration
D.Decreased intracellular Ca2+ concentration
E.Decreased intracellular Na+ concentration
5. Many biologic reactions are oxidation–reduction reactions that use a biologic electron carrier.
Which one of the following statements correctly describes reduction of one of these electron
carriers, NAD+ or FAD?
A.NAD+ accepts two electrons as hydrogen atoms to form NAD(2H).
B.NAD+ accepts two electrons that are each donated from a separate atom of the substrate.
C.NAD+ accepts two electrons as a hydride ion to form NADH.
D.FAD releases a proton as it accepts two electrons.
E.FAD must accept two electrons at a time.
6. Active transport is necessary to move compounds into or out of the cell or mitochondria. Transport
work can occur when ATP donates its phosphate group to a transport protein, thereby altering the
conformation of that protein. Which one of the following mechanisms allows this conformational
change to occur?
A.A gain of ionic interactions, which alter tertiary and/or quaternary structure of the protein
B.Loss of ionic interactions, thereby altering the proteins tertiary and/or quaternary structure
C.Loss of hydrogen bonds in the primary structure of the protein
D.Gain of hydrophobic interactions, leading to an alteration in the proteins tertiary and/or
quaternary structure
E.Loss of hydrophobic interactions, leading to an alteration in the proteins tertiary and/or
quaternary structure7. The ΔG0′ values are determined under standard biochemical conditions and reflect the energy either
required, or released, as a particular reaction proceeds. Given the ΔG0′ values below, determine the
overall ΔG0′ for the following reaction: creatine + ATP yields creatine phosphate + ADP The half reactions are
ATP + H2O yields ADP
+ inorganic phosphate ΔG0'= −7.3 kcal/mol Creatine phosphate + H2O yields creatine
+ inorganic phosphate ΔG0'= −10.3 kcal/mol
A.−3.0 kcal/mol
B.−10.3 kcal/mol
C.−17.6 kcal/mol
D.+3.0 kcal/mol
E.+10.3 kcal/mol
+17.6 kcal/mol
8. When athletes expend vast amounts of energy, they are sometimes seen on the sidelines using
supplemental oxygen. More than 90% of the O2 we breathe is used for the generation of which one of
the following?
A.ATP
B.ADP
C.NAD+
D.FAD
E.Acetyl-CoA
9. ATP is the cells’ major energy-carrying molecule, and in order for a cell to survive, the cell must be
able to regenerate ATP when ATP levels drop. Which one of the following statements accurately
describes an aspect of ATP metabolism?
A.ATP is more stable than ADP.
B.ATP has more positively charged phosphate groups than ADP.
C.Phosphate groups repel each other, which in ATP leads to strained bond formation.
D.Heat from ATP hydrolysis is used to drive energy requiring processes.
E.ATP is hydrolyzed directly in the cell.
10. All physiologic processes in living cells require energy transformation. Which one of the following
would be considered biochemical work using the high-energy phosphate bonds of ATP?
A.Contracting muscle fibers
B.Developing a Na+ gradient across a membrane
C.Transporting compounds against a concentration gradient
D.Converting toxic compounds to nontoxic compounds in the liver
E.Undergoing catabolic pathways
ANSWERS TO REVIEW QUESTIONS1. The answer is E. Both of the high-energy phosphate bonds in ATP are located between phosphate
groups (both the α- and β-phosphates, and the β- and γ-phosphates). The phosphate bond between
the α-phosphate and ribose (or adenosine) is not a high-energy bond (thus, A and B are incorrect);
and there is no phosphate between the ribose and adenine, or two hydroxyl groups in the ribose
ring; therefore, answers C and D are incorrect.
2. The answer is C. The change in enthalpy, ΔH, is the total amount of heat that can be released in a
reaction. The first law of thermodynamics states that the total energy of a system remains constant,
and the second law of thermodynamics states the universe tends toward a state of disorder (thus, A
and B are incorrect). Answer D is incorrect because ΔG0′ is the standard free-energy change
measured at 25°C and a pH of 7. Answer E is incorrect because a high-energy bond releases more
than about 7 kcal/mol of heat when it is hydrolyzed. The definition of a high-energy bond is based
on the hydrolysis of one of the high-energy bonds of ATP.
3. The answer is A. The concentration of the substrates and products influence the direction of a
reaction. Answer B is incorrect because reactions with a positive free energy, at 1 M
concentrations of substrate and product, will proceed in the reverse direction. Answer C is
incorrect because substrate and product concentrations do influence the free energy
of a reaction.
Answer D is incorrect because the free energy must be considered (in addition to the substrate and
product concentrations) to determine the direction of a reaction. Answer E is false; an enzyme’s
efficiency does not influence the direction of a reaction.
4.The answer is C. A heart attack results in decreased pumping of blood, and thus a decreased O2
supply to the heart (thus, A is incorrect). The lack of O2 leads to a lack of ATP (thus, B is
incorrect) owing to an inability to perform oxidative phosphorylation. The lack of ATP impairs the
working of Na+,K+-ATPase, which pumps sodium out of the cell in exchange for potassium.
Therefore, intracellular levels of sodium will increase as Na+ enters the cell through other
transport mechanisms (thus, E is incorrect). The high intracellular sodium concentration then
blocks the functioning of the Na+/H+ antiporter (which sends protons out of the cell in exchange
for sodium). Because intracellular sodium is high, the driving force for this reaction is lost, which
leads to increased intracellular H+, or a lower intracellular pH (thus, C is correct). The
intracellular pH also decreases because of glycolysis in the absence of O2, which produces lactic
acid. The loss of the sodium gradient, coupled with the lack of ATP, leads to increased calcium in
the cell (thus, D is incorrect) owing to an inability to pump calcium out.
5.The answer is C. NAD+ accepts two electrons as hydride ions to form NADH (thus, A and B are
incorrect). Answers D and E are incorrect because FAD can accept two single electrons from
separate atoms, together with protons, or FAD can accept a pair of electrons.
6.The answer is A. When a protein is phosphorylated, the most likely sites of phosphorylation are
the hydroxyl groups of serine, threonine, or tyrosine. Prior to phosphorylation, those hydroxyl
groups on the amino acid side chains can only participate in hydrogen bonds. When phosphorylated, the oxygen of the hydroxyl group is now covalently linked to the phosphate, which
has two negative charges. This allows this group to form ionic bonds, which were not available
prior to phosphorylation. The formation of ionic bonds then alters the tertiary and/or thequaternary structure of the protein. The addition of phosphate groups reduces the hydrophobicity
of this region of the protein, and the primary structure of the protein is the linear sequence of
amino acids and does not involve hydrogen bond formation.
7.The answer is D. ΔG0′ values are additive for a series of reactions. In order to generate the
overall reaction required, creatine + ATP yields ADP + creatine phosphate, the second reaction
listed in the question needs to be reversed. Upon reversing a reaction, the sign of the standard free
energy is reversed, in this case becoming +10.3 for the reaction creatine + inorganic phosphate
yields creatine phosphate + H2O. Upon summing the first reaction, and the reversed second
reaction, the overall reaction is obtained and the ΔG0′ = 10.3 − 7.3, or +3.0 kcal/mol.
8.The answer is A. More than 90% of the O2 we breathe is used for cellular respiration, the overall
process of transferring the electrons obtained from oxidizing fuels to oxygen in order to generate
ATP. When ATP energy is needed, a high-energy phosphate bond of ATP is cleaved, forming ADP.
NAD+ and FAD are electron-accepting coenzymes that accept electrons from fuels as they are
oxidized, and the electron carriers are reduced to NADH and FAD(2H). NADH and FAD(2H)
donate their electrons to the electron transfer chain in order to generate ATP via oxidative
phosphorylation. Generation of acetyl-CoA is only phase 1 of cellular respiration and does not by
itself generate ATP. In phase 2, oxidation of acetyl-CoA in the TCA cycle collects energy as
NADH and FAD(2H) in order to generate ATP.
9.The answer is C. The instability of the phosphoanhydride bonds arises from their negatively
charged phosphate groups that repel each other and strain their bonds. ATP has more negatively
charged phosphate groups (4) than ADP (3), reflective of ATP containing two high-energy bonds,
and ADP containing one high-energy bond. In the cell, ATP is not hydrolyzed directly; rather, it is
hydrolyzed in specific reactions that require energy to be pushed toward product formation. ATP
is also used to form phosphate intermediates that are then substrates for other reactions in a
metabolic pathway. The heat released from ATP hydrolysis is used for thermogenesis, but it cannot
be used to drive other energy-requiring processes.
10.The answer is D. Biochemical work occurs in anabolic pathways (synthesizing large molecules)
or when toxic compounds are converted to nontoxic compounds that can be excreted. Muscle fiber
contraction is mechanical work and generating a sodium gradient, or transporting compounds
against a concentration gradient, are considered transport work. Catabolic pathways lead to the
generation of ATP.Digestion, Absorption, and Transport of Carbohydrates 21
For additional ancillary materials related to this chapter, please visit thePoint. Carbohydrates are the largest source of dietary calories for most of the world’s population. The major
carbohydrates in the US diet are starch, lactose, and sucrose. The starches amylose and amylopectin are
polysaccharides composed of hundreds to millions of glucosyl units linked together through α-1,4- and
α-1,6-glycosidic bonds (Fig. 21.1). Lactose is a disaccharide composed of glucose and galactose, linked
together through a β-1,4-glycosidic bond. Sucrose is a disaccharide composed of glucose and fructose,
linked through an α-1,2-glycosidic bond. The digestive processes convert all of these dietary
carbohydrates to their constituent monosaccharides by hydrolyzing glycosidic bonds between the sugars.The digestion of starch begins in the mouth (Fig. 21.2). The salivary gland releases α-amylase, which
converts starch to smaller polysaccharides called α-dextrins. Salivary α-amylase is inactivated by the
acidity of the stomach (hydrochloric acid [HCl]). Pancreatic α-amylase and bicarbonate are secreted by
the exocrine pancreas into the lumen of the small intestine, where bicarbonate neutralizes the gastric
secretions. Pancreatic α-amylase continues the digestion of α-dextrins, converting them to disaccharides
(maltose), trisaccharides (maltotriose), and oligosaccharides called limit dextrins. Limit dextrins
usually contain four to nine glucosyl residues and an isomaltose branch (two
glucosyl residues attached
through an α-1,6-glycosidic bond).The digestion of the disaccharides lactose and sucrose, as well as further digestion of maltose,
maltotriose, and limit dextrins, occurs through disaccharidases attached to the membrane surface of the
brush border (microvilli) of intestinal epithelial cells. Glucoamylase hydrolyzes the α-1,4-bonds of
dextrins. The sucrase–isomaltase complex hydrolyzes sucrose, most of maltose, and almost all of the
isomaltose formed by glucoamylase from limit dextrins. Lactase-glycosylceramidase (β-glycosidase)
hydrolyzes the β-glycosidic bonds in lactose and glycolipids. A fourth disaccharidase complex,
trehalase, hydrolyzes the bond (an α-1,1-glycosidic bond) between two glucosyl units in the sugar
trehalose. The monosaccharides produced by these hydrolases (glucose, fructose, and galactose) are then
transported into the intestinal epithelial cells.
Dietary fiber, composed principally of polysaccharides, cannot be digested by enzymes in the human
intestinal tract. In the colon, dietary fiber and other nondigested carbohydrates may be converted to gases
(H2, CO2, and methane) and short-chain fatty acids (principally acetic acid, propionic acid, and butyric
acid) by bacteria in the colon.
Glucose, galactose, and fructose formed by the digestive enzymes are transported into the absorptive
epithelial cells of the small intestine by protein-mediated Na+-dependent active transport and
facilitative diffusion. Monosaccharides are transported from these cells into the blood and circulate to
the liver and peripheral tissues, where they are taken up by facilitative transporters. Facilitative transport
of glucose across epithelial cells and other cell membranes is mediated by a family of tissue-specificglucose transport proteins (GLUT 1 to GLUT 5). The type of transporter found in each cell reflects the
role of glucose metabolism in that cell. THE WAITING ROOM
Denise V. is a 20-year-old exchange student from Nigeria who has noted gastrointestinal bloating,
abdominal cramps, and intermittent diarrhea ever since arriving in the United States 6 months ago.
A careful history shows that these symptoms occur most commonly about 45 minutes to 1 hour after eating
breakfast but may occur after other meals as well. Dairy products, which were not a part of Denise’s diet
in Nigeria, were identified as the probable offending agent because her gastrointestinal symptoms
disappeared when milk and milk products were eliminated from her diet.
Deborah S.’s fasting and postprandial blood glucose levels are frequently above the normal range
in spite of good compliance with insulin therapy. Her physician has referred her to a dietician
skilled in training diabetic patients in the successful application of an appropriate American Diabetes
Association diet. As part of the program, Ms. S. is asked to incorporate foods containing fiber into her
diet, such as whole grains (e.g., wheat, oats, corn), legumes (e.g., peas, beans, lentils), tubers (e.g.,
potatoes, peanuts), and fruits.
Nina M. is a 13-month-old baby girl, the second child born to unrelated parents. Her mother had a
healthy, full-term pregnancy, and Nina’s birth weight was normal. She did not respond well to
breastfeeding and was changed entirely to a formula based on cows’ milk at 6 weeks.