Download Chapter Twenty Three

Chapter Twenty Three
Carbohydrate Metabolism
Outline
►
►
►
►
►
►
►
►
►
►
►
23.1 Digestion of Carbohydrates
23.2 Glucose Metabolism: An Overview
23.3 Glycolysis
23.4 Entry of Other Sugars into Glycolysis
23.5 The Fate of Pyruvate
23.6 Energy Output in Complete Catabolism of Glucose
23.7 Regulation of Glucose Metabolism and Energy
Production
23.8 Metabolism in Fasting and Starvation
23.9 Metabolism in Diabetes Mellitus
23.10 Glycogen Metabolism: Glycogenesis and
Glycogenolysis
23.11 Gluconeogenesis: Glucose from Noncarbohydrates
Prentice Hall © 2007
Chapter Twenty Three
2
23.1 Digestion of Carbohydrates
► The first stage in catabolism is digestion, the
breakdown of food into small molecules.
► Digestion entails the physical grinding, softening,
and mixing of food, as well as the enzyme-catalyzed
hydrolysis of carbohydrates, proteins, and fats.
► Digestion begins in the mouth, a-amylase in saliva
catalyzes hydrolysis of the glycosidic bonds in
carbohydrates. Salivary a-amylase continues to act
on polysaccharides in the stomach until, after an
hour or so, it is inactivated by stomach acid. No
further carbohydrate digestion takes place in the
stomach.
Prentice Hall © 2007
Chapter Twenty Three
3
► a-Amylase is secreted by the
pancreas and enters the small
intestine, where conversion of
polysaccharides to maltose
continues.
► Enzymes from the mucous
lining of the small intestine
hydrolyze maltose, sucrose
and lactose to glucose,
fructose, and galactose, which
are then transported across
the intestinal wall into the
bloodstream.
Prentice Hall © 2007
Chapter Twenty Three
4
23.2 Glucose Metabolism: An
Overview
► When glucose enters a cell from the bloodstream, it
is immediately converted to glucose 6-phosphate.
► Once this phosphate is formed, glucose is trapped
within the cell because phosphorylated molecules
cannot cross the cell membrane.
► Like the first step in many metabolic pathways, the
formation of glucose-6-phosphate is highly
exergonic and not reversible in the glycolytic
pathway, thereby committing the initial substrate to
subsequent reactions.
Prentice Hall © 2007
Chapter Twenty Three
5
► Glucose-6-phosphate can enter the pentose
phosphate pathway. This multistep pathway yields
two products of importance to our metabolism.
► One is a supply of the coenzyme NADPH, a
reducing agent that is essential for various
biochemical reactions.
► The other is ribose 5-phosphate, which is necessary
for the synthesis of nucleic acids (DNA and RNA).
► Glucose-6-phosphate enters the pentose phosphate
pathway when a cell’s need for NADPH or ribose-5phosphate exceeds its need for ATP.
Prentice Hall © 2007
Chapter Twenty Three
6
► When cells are already well supplied with glucose,
the excess glucose is converted to other forms for
storage: to glycogen, the glucose storage polymer, by
the glycogenesis pathway, or to fatty acids by
entrance of acetyl-SCoA into the pathways of lipid
metabolism rather than the citric acid cycle.
► When energy is needed, glucose 6-phosphate
undergoes glycolysis to pyruvate and then to acetylS-coenzyme A, which enters the citric acid cycle.
Prentice Hall © 2007
Chapter Twenty Three
7
Glucose 6phosphate can
be converted
to pentose
products,
stored as
glycogen, or
broken down
to acetylSCoA for
production of
energy,
proteins, or
fats.
Prentice Hall © 2007
Chapter Twenty Three
8
23.3 Glycolysis
► Glycolysis is a series of 10 enzyme-catalyzed
reactions that break down glucose molecules.
► The net result of glycolysis is the production of two
pyruvate molecules, two ATPs, and two NADH/H+s.
Prentice Hall © 2007
Chapter Twenty Three
9
► Steps 1-5 of
glycolysis break
one glucose
molecule down
into two
D-glyceraldehyde
3-phosphate
fragments.
► An investment of
2 ATP molecules
is required.
Prentice Hall © 2007
Chapter Twenty Three
10
►Steps 6-10
occur twice
for each
glucose that
enters in at
step 1.
►Steps 6-10
produce:
2 pyruvates,
4 ATPs
2 NADH/H+
per glucose.
Prentice Hall © 2007
Chapter Twenty Three
11
23.4 Entry of Other Sugars into
Glycolysis
► The major monosaccharides from digestion other
than glucose also eventually join the glycolysis
pathway.
► Fructose, from fruits or hydrolysis of the
disaccharide sucrose, is converted to glycolysis
intermediates in two ways:
- In muscle, it is phosphorylated to fructose 6phosphate.
- In the liver, it is converted to glyceraldehyde 3phosphate.
Prentice Hall © 2007
Chapter Twenty Three
12
Mannose is a product of the hydrolysis of plant
polysaccharides other than starch.
Prentice Hall © 2007
Chapter Twenty Three
13
► Mannose is converted by hexokinase to a 6phosphate, which then undergoes a multistep,
enzyme-catalyzed rearrangement and enters
glycolysis as fructose 6-phosphate.
► Galactose from hydrolysis of the disaccharide
lactose is converted to glucose 6- phosphate by a
five-step pathway.
► A hereditary defect affecting any enzyme in this
pathway can be a cause of galactosemia.
Prentice Hall © 2007
Chapter Twenty Three
14
23.5 The Fate of Pyruvate
► The conversion of
glucose to pyruvate is a
central metabolic
pathway in most living
systems.
► The further reactions of
pyruvate depend on
metabolic conditions
and on the nature of the
organism.
Prentice Hall © 2007
Chapter Twenty Three
15
► Aerobic: In the presence of oxygen.
► Under normal oxygen-rich (aerobic) conditions,
pyruvate is converted to acetyl-SCoA.
► Pyruvate diffuses across the outer mitochondrial
membrane, then is carried by a transporter protein
across the inner mitochondrial membrane.
► Once inside, pyruvate dehydrogenase complex
catalyzes the conversion of pyruvate to acetyl-SCoA.
Prentice Hall © 2007
Chapter Twenty Three
16
► Anaerobic: In the absence of oxygen.
► If electron transport slows because of insufficient
oxygen, NADH concentration increases, NAD+ is in
short supply, and glycolysis cannot continue.
► An alternative way to reoxidize NADH is essential
because glycolysis, the only available source of fresh
ATP, must continue. The reduction of pyruvate to
lactate solves the problem.
Prentice Hall © 2007
Chapter Twenty Three
17
► NADH serves as the reducing agent and is reoxidized
to NAD+ which is then available in the cytosol for
glycolysis. Lactate formation serves no purpose other
than NAD+ production, and the lactate is reoxidized
to pyruvate when oxygen is available.
► Microorganisms often must survive in the absence of
oxygen and have evolved numerous anaerobic
strategies for energy production, generally known as
fermentation.
► When pyruvate undergoes fermentation by yeast, it is
converted into ethanol plus carbon dioxide. This
process, known as alcoholic fermentation, is used to
produce beer, wine, and other alcoholic beverages
and also to make bread.
Prentice Hall © 2007
Chapter Twenty Three
18
23.6 Energy Output in Complete
Catabolism of Glucose
► The total energy output from oxidation of glucose is
the combined result of
- (a) glycolysis
- (b) conversion of pyruvate to acetyl-SCoA
- (c) conversion of two acetyl groups to four
molecules of CO2 in the citric acid cycle
- (d) the passage of reduced coenzymes from each
of these pathways through electron transport and
the production of ATP by oxidative
phosphorylation.
Prentice Hall © 2007
Chapter Twenty Three
19
► The sum of the net equations for each pathway that
precedes oxidative phosphorylation is shown below.
► Since each glucose yields 2 pyruvates and 2 acetylSCoAs, the net equations for pyruvate oxidation and
the citric acid cycle are multiplied by 2.
Prentice Hall © 2007
Chapter Twenty Three
20
► The total number of ATPs per glucose molecule is the
4 ATPs from glucose catabolism plus the number of
ATPs produced for each reduced coenzyme that enters
electron transport.
► For a long time, based on the belief that 3 ATPs are
generated per NADH and 2 ATPs per FADH2 the
maximum yield was taken as 38 ATPs.
► 10 NADH(3ATP/NADH) + 2 FADH2(2ATP/FADH2)
+ 4 ATP = 38 ATP
► The 38 ATPs per glucose molecule are viewed as a
maximum yield of ATP, most likely possible in
bacteria and other prokaryotes. In humans and other
mammals, the maximum is most likely 30–32 ATPs
per glucose molecule.
Prentice Hall © 2007
Chapter Twenty Three
21
23.7 Regulation of Glucose Metabolism
and Energy Production
► Normal blood glucose
concentration a few hours
after a meal ranges roughly
from 65 to 110 mg/dL.
► Hypoglycemia: Lower-than
normal blood glucose
concentration.
► Hyperglycemia: Higherthan normal blood glucose
concentration.
Prentice Hall © 2007
Chapter Twenty Three
22
► Low blood glucose (hypoglycemia) causes
weakness, sweating, and rapid heartbeat, and in
severe cases, low glucose in brain cells causes
mental confusion, convulsions, coma, and eventually
death. The brain can use only glucose as a source of
energy. At a blood glucose level of 30 mg/dL,
consciousness is impaired or lost, and prolonged
hypoglycemia can cause permanent dementia.
► High blood glucose (hyperglycemia) causes
increased urine flow as the normal osmolarity
balance of fluids within the kidney is disturbed.
Prolonged hyperglycemia can cause low blood
pressure, coma, and death.
Prentice Hall © 2007
Chapter Twenty Three
23
► Two hormones from the pancreas have the major
responsibility for blood glucose regulation.
► The first, insulin, is released when blood glucose
concentration rises.
► The second hormone, glucagon, is released when
blood glucose concentration drops.
Prentice Hall © 2007
Chapter Twenty Three
24
23.8 Metabolism in Fasting and
Starvation
► The metabolic changes in the absence of food begin
with a gradual decline in blood glucose
concentration accompanied by an increased release
of glucose from glycogen.
► All cells contain glycogen, but most is stored in liver
cells (about 90 g in a 70-kg man) and muscle cells
(about 350 g in a 70-kg man). Free glucose and
glycogen represent less than 1% of our energy
reserves and are used up in 15–20 hours of normal
activity (3 hours in a marathon race).
Prentice Hall © 2007
Chapter Twenty Three
25
►During the first few
days of starvation,
protein is used up at a
rate as high as 75 g/day.
►Lipid catabolism is
mobilized, and acetylSCoA molecules
derived from
breakdown of lipids
accumulate.
►Acetyl-SCoA begins to
be removed by a new
series of metabolic
reactions that transform
it into ketone bodies.
Prentice Hall © 2007
Chapter Twenty Three
26
As starvation continues, the brain and other tissues are
able to switch over to producing up to 50% of their
ATP from catabolizing ketone bodies instead of
glucose. By the 40th day of starvation, metabolism has
stabilized at the use of about 25 g of protein and 180 g
of fat each day. So long as adequate water is available,
an average person can survive in this state for several
months; those with more fat can survive longer.
Prentice Hall © 2007
Chapter Twenty Three
27
23.9 Metabolism in Diabetes Mellitus
► Diabetes mellitus: A chronic condition due to either
insufficient insulin or failure of insulin to activate
crossing of cell membranes, by glucose.
► The symptoms by which diabetes is usually detected
are excessive thirst accompanied by frequent
urination, abnormally high glucose concentrations in
urine and blood, and wasting of the body despite a
good diet. These symptoms result when available
glucose does not enter cells where it is needed.
Prentice Hall © 2007
Chapter Twenty Three
28
► Type II diabetes is thought to result when cell
membrane receptors fail to recognize insulin. Drugs
that increase either insulin or insulin receptor levels
are an effective treatment because more of the
undamaged receptors are put to work.
► Type I diabetes is classified as an autoimmune
disease, a condition in which the body misidentifies
some part of itself as an invader. Gradually, the
immune system wrongly identifies pancreatic beta
cells as foreign matter, develops antibodies to them,
and destroys them. To treat Type I diabetes, the
missing insulin must be supplied by injection.
Prentice Hall © 2007
Chapter Twenty Three
29
► Diabetic individuals are subject to several serious
conditions that result from elevated blood glucose
levels. Excess glucose is reduced to sorbitol.
► Sorbitol is not transported out of the cell. Its rising
concentration increases the osmolarity of fluid in the
eye, causing increased pressure, cataracts, and
blindness. Elevated sorbitol is also associated with
blood vessel lesions and gangrene in the legs.
► Ketoacidosis results from the buildup of acidic
ketones in the late stages of uncontrolled diabetes. It
can lead to coma and diminished brain function.
► Hypoglycemia by contrast, may be due to an
overdose of insulin or failure to eat. Diabetic
hypoglycemia can cause nerve damage or death.
Prentice Hall © 2007
Chapter Twenty Three
30
23.10 Glycogen Metabolism:
Glycogenesis and Glycogenolysis
► Glycogen synthesis, known as glycogenesis, occurs
when glucose concentrations are high.
► Glucose 6-phosphate is first isomerized to glucose 1phosphate.
► The glucose residue is then attached to uridine
diphosphate (UDP):
Prentice Hall © 2007
Chapter Twenty Three
31
The resulting glucose-UDP transfers glucose to a
growing glycogen chain in an exergonic reaction.
Prentice Hall © 2007
Chapter Twenty Three
32
►Glycogenolysis: The
biochemical pathway
for breakdown of
glycogen to free
glucose.
►Glycogenolysis occurs
in muscle cells when
there is an immediate
need for energy.
►Glycogenolysis occurs
in the liver when blood
glucose is low.
Prentice Hall © 2007
Chapter Twenty Three
33
23.11 Gluconeogenesis: Glucose from
Noncarbohydrates
► Gluconeogenesis, which occurs mainly in the liver,
is the pathway for making glucose from
noncarbohydrate molecules—lactate, amino acids,
and glycerol.
► This pathway becomes critical during fasting and the
early stages of starvation. Failure of gluconeogenesis
is usually fatal.
► During exercise lactate produced in muscles under
anaerobic conditions during exercise is sent to the
liver, where it is converted back to glucose.
Prentice Hall © 2007
Chapter Twenty Three
34
Gluconeogenesis requires energy, so shifting this
pathway to the liver frees the muscles from the
burden of having to produce even more energy.
Prentice Hall © 2007
Chapter Twenty Three
35
► Steps 1, 3, and 10 in glycolysis are too exergonic to
be directly reversed. Gluconeogenesis uses reactions
catalyzed by different enzymes that reverse these
steps. The 7 other steps of glycolysis are reversible
because they operate at near-equilibrium conditions.
► Gluconeogenesis begins with conversion of pyruvate
to phosphoenolpyruvate, the reverse of the highly
exergonic step 10 of glycolysis. Two steps are
required, utilizing two enzymes and the energy
provided by two triphosphates, ATP and GTP.
Prentice Hall © 2007
Chapter Twenty Three
36
Chapter Summary
► Carbohydrate digestion, the hydrolysis of
disaccharides and polysaccharides, begins in the
mouth and continues in the stomach and small
intestine. The products that enter the bloodstream
from the small intestine are monosaccharides—
mainly glucose, fructose, and galactose.
► Glucose is converted to glucose 6-phosphate and
undergoes glycolysis to pyruvate, which is fed into
the citric acid cycle via acetyl-SCoA. One alternative
pathway for glucose is glycogenesis, the synthesis of
glycogen. Another is the pentose phosphate pathway,
which provides the five-carbon sugars and NADPH
needed for biosynthesis.
Prentice Hall © 2007
Chapter Twenty Three
37
Chapter Summary Cont.
► Glycolysis is a 10-step pathway that produces two
molecules of pyruvate, two reduced coenzymes
(NADH), and two ATPs for each molecule of
glucose metabolized.
► When oxygen is in good supply, pyruvate is
transported into mitochondria and converted to
acetyl-SCoA for energy generation via the citric acid
cycle and oxidative phosphorylation.
► When there is insufficient oxygen, pyruvate is
reduced to L-lactate, with the production of the
oxidized coenzyme NAD+ that is essential to the
continuation of glycolysis.
► In the presence of yeast, pyruvate undergoes
anaerobic fermentation to yield ethyl alcohol.
Prentice Hall © 2007
Chapter Twenty Three
38
Chapter Summary Cont.
► Insulin, produced when blood glucose concentration
rises, accelerates glycolysis and glycogen synthesis.
Glucagon, produced when blood glucose
concentration drops, accelerates production of
glucose in the liver from stored glycogen and from
other precursors via the gluconeogenesis pathway.
► Adaptation to starvation begins with the effects of
glucagon and energy production from protein, and
then proceeds to reliance on ketone bodies from fatty
tissue for energy generation.
► Diabetes mellitus may be insulin-dependent or noninsulin-dependent. Among the serious outcomes of
uncontrolled diabetes are cataracts, blood vessel
lesions, ketoacidosis, and hypoglycemia.
Prentice Hall © 2007
Chapter Twenty Three
39
Chapter Summary Cont.
► Glycogenesis, the synthesis of the polysaccharide
glycogen, puts excess glucose into storage, mainly in
muscles and the liver.
► Glycogenolysis is the release of stored glucose from
glycogen. Glycogenolysis occurs in muscles when
there is an immediate need for energy. It occurs in
the liver when blood glucose concentration is low.
► Gluconeogenesis maintains glucose levels by
synthesizing it from lactate, from certain amino acids
derived from proteins, and from glycerol derived
from fatty tissue; it is critical during fasting and
starvation.
Prentice Hall © 2007
Chapter Twenty Three
40
End of Chapter 23
Prentice Hall © 2007
Chapter Twenty Three
41