Chapter 23 Carbohydrate Metabolism
1.!
What happens during digestion of carbohydrates? Be able to describe
carbohydrate digestion, its location, the enzymes involved, and name the major
products of this process.!
2.!
What are the major pathways in the metabolism of glucose? Be able to identify
the pathways by which glucose is (1) synthesized and (2) broken down, and describe
their interrelationships.!
3.!
What is glycolysis? Be able to give an overview of the glycolysis pathway and its
products, and to identify where the major monosaccharides enter the pathway.
4.!
What happens to pyruvate once it is formed? Be able to describe the pathways
involving pyruvate and their respective outcomes.!
5.!
How is glucose metabolism regulated, and what are the influences of starvation
and diabetes mellitus? Be able to identify the hormones that influence glucose
metabolism and describe the changes in metabolism during starvation and diabetes
mellitus.!
6.!
What are glycogenesis and glycogenolysis? Be able to define these pathways and
their purpose.!
7.!
What is the role of gluconeogenesis in metabolism? Be able to identify the
functions, substrates, and products of this pathway.
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Digestion:
Digestion entails the physical grinding, softening, and mixing of food, as
well as the enzyme-catalyzed hydrolysis of carbohydrates, proteins,
and fats.
! -amylase:
Digestion begins in the mouth, ! -amylase in saliva catalyzes hydrolysis
of the glycosidic bonds in carbohydrates. Salivary ! -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.
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.
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Pentose phosphate pathway:
1.
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2.
Glucose-6-phosphate enters the pentose phosphate pathway when a
cellʼs need for NADPH or ribose-5-phosphate exceeds its need for
ATP.
Glycogenesis Pathway:
Glycolysis Pathway:
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Glucose 6-phosphate can be converted to pentose products, stored as
glycogen, or broken down to acetyl- SCoA for production of energy,
proteins, or fats.
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Glycolysis:
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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 6-phosphate.
In the liver, it is converted to glyceraldehyde 3-phosphate.
Mannose is a product of the hydrolysis of plant polysaccharides other
than starch.
Mannose is converted by hexokinase to a 6-phosphate, which then
undergoes a multistep, enzyme-catalyzed rearrangement and
enters glycolysis as fructose 6-phosphate.
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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 .
Aerobic:
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Anaerobic:
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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.
Fermentation:
Alcoholic Fermentation:
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The total energy output from oxidation of glucose is the combined result
of
(a)
(b)
(c)
(d)
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.
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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 is 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.
Normal blood glucose concentration a few hours after a meal ranges
roughly from 65 to 110 mg/ dL .
Hypoglycemia:
Hyperglycemia:
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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.
Two hormones from the pancreas have the major responsibility for
blood glucose regulation.
Insulin:
Glucagon:
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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).
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 acetyl- SCoA 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.
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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.
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Diabetes mellitus:
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.
Type I:
Type II:
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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:
Hypoglycemia:
Glycogenesis:
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Glycogenolysis:
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Gluconeogenesis:
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.
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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.
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