Chapter 24
Carbohydrate
Metabolism
Chapter 24
Table of Contents
24.1
24.2
24.3
24.4
24.5
24.6
24.7
24.8
24.9
24.10
24.11
24.12
24.13
24.14
Digestion and Absorption of Carbohydrates
Hormonal Control of Carbohydrate Metabolism
Glycogen Synthesis and Degradation
Gluconeogenesis
The Pentose Phosphate Pathway
Glycolysis
Terminology for Glucose Metabolic Pathways
The Citric Acid Cycle
The Electron Transport Chain
Oxidative Phosphorylation
ATP Production for the Complete Oxidation of Glucose
Importance of ATP
Non-ETC Oxygen-Consuming Reactions
B-Vitamins and Carbohydrate Metabolism
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Section 24.1
Digestion and Absorption of Carbohydrates
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Section 24.1
Digestion and Absorption of Carbohydrates
• Carbohydrate digestion: Begins in the mouth
– Salivary enzyme “α-amylase” catalyzes the hydrolysis of αglycosidic linkages of starch and glycogen to produce smaller
polysaccharides and disaccharide – maltose
– Only a small amount of carbohydrate digestion occurs in the
mouth because food is swallowed so quickly into the stomach
• In stomach very little carbohydrate is digested:
– No carbohydrate digestion enzymes present in stomach
– Salivary amylase gets inactivated because of stomach acidity
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Section 24.1
Digestion and Absorption of Carbohydrates
• The primary site for the carbohydrate digestion is within
the small intestine
– Pancreatic α-amylase breaks down polysaccharide chains into
disaccharide – maltose
• The final step in carbohydrate digestion occurs on the
outer membranes of intestinal mucosal cells
– Maltase – hydrolyses maltose to glucose
– Sucrase – hydrolyses sucrose to glucose and fructose
– Lactase – hydrolyses lactose to glucose and galactose
• Glucose, galactose, and fructose are absorbed into the
bloodstream through the intestinal wall.
• Galactose and Fructose are converted to products of
glucose metabolism in the liver.
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Section 24.1
Digestion and Absorption of Carbohydrates
• Following absorption the monosaccharides are carried by the
portal vein to the liver where galactose and fructose are
enzymatically converted to glucose intermediates that enter
into the glycolysis pathway
• The glucose may then pass into the general circulatory
system to be transported to the tissues or converted to
glycogen reserve in the liver.
• The glucose in the tissues may be
a) oxidized to CO2 and H2O (ATP)
b) converted to fat
c) converted to muscle glycogen
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Section 23.1
Metabolism
•
Blood-sugar level:
–
–
•
•
Abnormal conditions:
A. hypoglycemia
–
–
–
•
the proper functions of the body are dependent on precise control of the glucose
concentration in the blood.
the normal fasting level of glucose in the blood is 70-90 mg/100 ml.
condition resulting from a lower than the normal blood-sugar level (below 70 mg/100 ml)
extreme hypoglycemia, usually due to the presence of excessive amounts of insulin, is
characterized by general weakness, trembling, drowsiness, headache, profuse perspiration,
rapid heart beat, lowered blood pressure and possible loss of consciousness.
Loss of consciousness is most likely due to the lack of glucose in the brain tissue, which is
dependent upon this sugar for its energy.
B. hyperglycemia
–
–
–
higher than the normal level (above 120 mg/100 mL); when the pancreas does not secrete
enough insulin
may temporarily exist as a result of eating a meal rich in carbohydrates.
extreme hyperglycemia, the renal threshold (160-170 mg/100 mL) is reached and excess
glucose is excreted in the urine
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Section 24.9
Hormonal Control of Carbohydrate Metabolism
• Besides enzyme inhibition, carbohydrate metabolism may be
regulated by hormones
• Three major hormones control carbohydrate metabolism:
– Insulin ; Glucagon ; Epinephrine
• Insulin
•
•
•
•
•
51 amino acid polypeptide secreted by the pancreas
Promotes utilization of glucose by cells
The release of insulin is triggered by high blood-glucose levels
Its function is to lower blood glucose levels by enhancing the formation of
glycogen from glucose (glycogen synthesis)
The mechanism for insulin action involves insulin binding to proteins
receptors on the outer surfaces of cells which facilitates entry of the glucose
into the cells
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Section 24.9
Hormonal Control of Carbohydrate Metabolism
Glucagon
• 29 amino acid peptide hormone produced in the pancreas
• Released when blood glucose levels are low
• Principal function is to increase blood-glucose concentration by
speeding up the conversion of glycogen to glucose (glycogenolysis)
in the liver
• Glucagon elicits the opposite effects of insulin
Epinephrine (also called adrenaline)
•
•
•
•
Released by the adrenal glands in response to anger, fear, or excitement
Function is similar to glucagon, i.e., stimulates glycogenolysis
Primary target of epinephrine is muscle cells
Promotes energy generation for quick action
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Section 23.1
Metabolism
• There are six major
metabolic pathways
of glucose:
1) Glycogenesis
2) Glycogenolysis
3) Gluconeogenesis
4) Hexose monophosphate
shunt
5) Glycolysis
6) Citric Acid Cycle
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Section 24.5
Glycogen Synthesis and Degradation
Glycogenesis and Glycogenolysis
• Involved in the regulation of blood glucose concentration
• When the dietary intake of glucose exceeds immediate needs,
humans and other animals can convert the excess to glycogen,
which is stored in either the liver or muscle tissue.
• Glycogenesis is the pathway that converts glucose into glycogen.
• When there’s need for additional blood glucose, glycogen is
hydrolyzed and released into the bloodstream.
• Glycogenolysis is the pathway that hydrolyzes glycogen to
glucose.
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Section 24.6
Gluconeogenesis
•
•
•
•
•
•
Metabolic pathway by which glucose is synthesized from noncarbohydrate sources:
– The process is not exact opposite of glycolysis
Glycogen stores in muscle and liver tissue are depleted with in 12-18 hours
from fasting or in even less time from heavy work or strenuous physical
activity
Without gluconeogenesis, the brain, which is dependent on glucose as a
fuel would have problems functioning if food intake were restricted for even
one day
Gluconeogenesis helps to maintain normal blood-glucose levels in times of
inadequate dietary carbohydrate intake
About 90% of gluconeogenesis takes place in the liver
Non-carbohydrate starting materials for gluconeogenesis:
–
–
–
–
Pyruvate
Lactate (from muscles and from red blood cells)
Glycerol (from triacylglycerol hydrolysis)
Certain amino acids (from dietary protein hydrolysis or from muscle protein
during starvation)
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Section 24.8
The Pentose Phosphate Pathway
Hexose monophosphate shunt
•
•
•
•
Initial reactant of the pathway is glucose-6phosphate
Also termed phosphogluconate pathway,
because 6–phosphogluconate is one of the
intermediates
A third name is pentose phosphate pathway,
because ribose-5-phosphate is one of its
products
The main purposes of the HMP shunt are the
following:
– to produce ribose-5-P for nucleotide
synthesis
– to produce NADPH from NADP+ for fatty
acid and steroid biosynthesis and for
maintaining reduced glutathione (GSH)
inside erythrocytes
– to interconvert pentoses and hexoses
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Section 24.2
Glycolysis
•
•
•
•
A series of reactions in the
cytoplasm which converts
glucose (C6) to two molecules of
pyruvate (a C3 carboxylate), and
ATP and NADH are produced.
Also called Embden-Meyerhof
pathway, after the scientist who
elucidated the pathway
an anaerobic process; each
step takes place without O2; one
of its advantages, the body can
obtain energy from glycolysis
quickly, without waiting for a
supply of O2 to be carried to the
cells.
occurs in cells lacking
mitochondria, e.g., erythrocytes
and in certain skeletal muscle
cells during intense muscle
activity
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Section 24.2
Glycolysis
•
•
•
•
•
•
Step 1: Formation of glucose-6-phosphate:
– Endothermic reaction catalyzed by
hexokinase
– Energy needed is derived from ATP
hydrolysis
Step 2: Formation of Fructose-6-phosphate:
– Enzyme: Phosphoglucoisomerase
Step 3: Formation of Fructose 1,6-bisphosphate:
– Enzyme: phosphofructokinase
Step 4: Formation of Triose Phosphates:
– C6 species is split into two C3 species
– Enzyme : Aldolase
Step 5: Isomerization of Triose Phosphates
– DHAP is isomerized to glyceraldehyde 3phosphate
– Enzyme: Triosephosphate isomerase
Step 6: Formation of 1,3-bisphosphoglycerate
– Glyceraldehyde 3-phosphate is oxidized and
phosphorylated
– Enzyme: Glyceraldehyde-3-phosphate
dehydrogenase
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Section 24.2
Glycolysis
•
•
•
•
•
•
Step 7: Formation of 3-bisphosphoglycerate
– It is an ATP producing step
– Enzyme: phosphoglycerokinase
Step 8: Formation of 2-phosphoglycerate
– Isomerization of 3-phosphoglycerate to
2-phosphoglycerate
– Enzyme: phosphoglyceromutase
Step 9: Formation of Phosphoenolpyruvate:
– Enzyme: Enolase
Step 10: Formation of Pyruvate:
– High energy phosphate is transferred
from phosphoenolpyruvate to ADP
molecule to produce ATP and pyruvate
– Enzyme: Pyruvate kinase
At this point of carbohydrate metabolism
there are at least 2 directions that the
product pyruvate may take.
The direction depends primarily upon the
availability of oxygen in the cell:
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Section 24.2
Glycolysis
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Section 24.2
Glycolysis
•
•
•
•
•
•
If there is adequate oxygen, an aerobic
pathway is followed and pyruvate
enters the Krebs cycle.
If there is insufficient oxygen available,
the anaerobic pathway is continued
and pyruvate undergoes a series of
reactions to produce lactic acid.
Lactic acid then is the end-product of
glycolysis, and if there were not some
mechanism for its removal, it would
accumulate in the muscle cells & cause
muscle “crumps”.
Bacteria also use lactate fermentation
in the production of yogurt and cheese
Reactions 1  9 are identical for
glycolysis and alocoholic fermentation
for pyruvic acid, the crossroads
compound, its metabolic fate depends
upon the conditions (aerobic or
anaerobic) and upon the organism
under consideration.
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Section 24.2
Glycolysis
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Section 24.6
Gluconeogenesis
The Cori cycle. Lactate, formed from
glucose under anaerobic conditions in
muscle cells (glycolysis), is transferred
to the liver, where it is reconverted to
glucose (gluconeogenesis), which is
then transferred back to the muscle
cells.
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Section 24.7
Terminology For Glucose Metabolic Pathways
Relationships Among Four Common Metabolic Pathways That
Involve Glucose
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Section 24.2
Glycolysis
ATP Production and Consumption
• There is a net gain of two ATP molecules in glycolysis for every
glucose molecule processed
• Overall equation for glycolysis
G lucose + 2NAD+
2ADP + 2Pi
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2 Pyr uvate + 2NADH + 2H+ + 2H2O
2A T P
22
Section 23.7
The Citric Acid Cycle
•
•
•
•
Citric acid cycle: A series of
biochemical reactions in which the
acetyl portion of acetyl CoA is
oxidized to carbon dioxide and ATP
and the reduced coenzymes FADH2
and NADH are produced
Takes place in the mitochondria
Also known as tricarboxylic acid
cycle (TCA) or Krebs cycle:
– Named after Hans Krebs who
elucidated this pathway
Two important types of reactions:
– Reduction of NAD+ and FAD to
produce NADH and FADH2
– Decarboxylation of citric acid to
produce carbon dioxide
– The citric acid cycle also
produces 2 ATP by substrate
level phosphorylation from GTP
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Section 23.7
The Citric Acid Cycle
•
•
•
•
•
•
•
•
Step 1: Formation of Citrate
Step 2: Formation of
Isocitrate
Step 3: Oxidation of Isocitrate
and Formation of CO2:
involves oxidation–reduction
as well as decarboxylation
Step 4: Oxidation of AlphaKetoglutarate and Formation
of CO2
Step 5: Thioester bond
cleavage in Succinyl CoA
and Phosphorylation of GDP
to form GTP
Step 6: Oxidation of
Succinate
Step 7: Hydration of
Fumarate
Step 8: Oxidation of L-Malate
to regenerate Oxaloacetate
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Section 23.7
The Citric Acid Cycle
•
•
•
•
•
•
•
•
•
Important features of the cycle:
The reactions of the cycle takes place in the mitochondrial matrix, except the succinate
dehydrogenase reaction that involves FAD. The enzyme that catalyzes this reaction is an
integral part of the inner mitochondrial membrane.
The “fuel “ for the cycle is acetyl CoA, obtained from the breakdown of carbohydrates, fats,
and proteins.
Four of the cycle reactions involve oxidation and reduction. The oxidizing agent is either
NAD+ (three times) or FAD (once). The operation of the cycle depends on the availability of
these oxidizing agents.
In redox reactions, NAD+ is the oxidizing agent when a carbon-oxygen double bond is
formed; FAD is the oxidizing agent when a carbon-carbon double bond is formed.
The three NADH and the one FADH2 that are formed during the cycle carry electrons and
H+ to the electron transport chain through which ATP is synthesized.
Two carbon atoms enter the cycle as acetyl unit of the acetyl CoA, and two carbon atoms
leave the cycle as two molecules of CO2. The carbon atoms that enter and leave are not
the same ones. The carbon atoms that leave during one turn of the cycle are carbon atoms
that entered during the previous turn of the cycle.
Four B vitamins are necessary for the proper functioning of the cycle: riboflavin (in both
FAD and α-ketoglutarate dehydrogenase complex), nicotinamide (in NAD+), pantothenic
acid (in CoASH), and thiamin (in α-ketoglutarate dehydrogenase complex)
One high-energy GTP molecule is produced by substrate level phosphorylation.
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Section 23.7
The Citric Acid Cycle
Regulation of the Citric Acid Cycle
• The rate at which the citric acid cycle operates is controlled by ATP
and NADH levels
• When ATP supply is high, ATP inhibits citrate synthase (Step 1 of
Citric acid cycle)
• When ATP levels are low, ADP activates citrate synthase
• Similarly ADP and NADH control isocitrate dehydrogenase:
– NADH acts as an inhibitor
– ADP as an activator.
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Section 23.8
The Electron Transport Chain
• The electron transport chain (ETC) facilitates the passage of
electrons trapped in FADH2 and NADH during citric cycle
• ETC is a series of biochemical reactions in which intermediate
carriers (protein and non-protein) aid the transfer of electrons and
hydrogen ions from NADH and FADH2
• The ultimate receiver of electrons is molecular oxygen
• The electron transport (respiratory chain) gets its name from the fact
that electrons are transported to oxygen absorbed via respiration
• ETC is the sequence of reactions whereby the reduced forms of the
coenzymes are reoxidized, ultimately by O2
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Section 23.8
The Electron Transport Chain
• The enzymes and electron carriers needed for the ETC
are located along inner mitochondrial membrane
• They are organized into four distinct protein complexes
and two mobile carriers
• The four protein complexes tightly bound to membrane:
• Complex 1: NADH-coenzyme Q reductase
• Complex II: Succinate-coenzyme Q reductase
• Complex III: Coenzyme Q - cytochrome C reductase
• Complex IV: Cytochrome C oxidase
• Two mobile electron carriers are:
– Coenzyme Q and cytochrome c.
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Section 23.8
The Electron Transport Chain
Complex I: NADHCoenzyme Q Reductase
•
Facilitates transfer of
electrons from NADH
to coenzyme Q
Complex II: SuccinateCoenzyme Q Reductase
•
•
•
Succinate is converted
to fumarate by this
complex
In the process it
generates FADH2
CoQ is the final
recipient of the
electrons from FADH2
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Section 23.8
The Electron Transport Chain
Complex III: Coenzyme Q –
Cytochrome c Reductase
•
•
Several iron-sulfur proteins
and cytochromes are electron
carriers in this complex
Cytochrome is a heme iron
protein in which reversible
oxidation of an iron atom
occurs
Complex IV: Coenzyme Q –
Cytochrome c Reductase
•
•
•
The electrons flow from cyt c to
cyt a to cyt a3
In the final stage of electron
transfer, the electrons from cyt
a3, and hydrogen ion (H+)
combine with oxygen (O2) to
form water
O2 + 4H+ + 4e-  2 H2O
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Section 23.8
The Electron Transport Chain
• Summary of the flow of electrons through four
complexes of the electron transport chain.
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Section 23.9
Oxidative Phosphorylation
• Oxidative phosphorylation – process by which ATP
is synthesized from ADP and Pi using the energy
released in the electron transport chain by coupled
reactions
• Coupled Reactions -- are pairs of biochemical
reactions that occur concurrently in which energy
released by one reaction is used in the other
reaction
– example: oxidative phosphorylation and the
oxidation reactions of the electron transport
chain are coupled systems
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Section 23.9
Oxidative Phosphorylation
•
•
•
•
•
The coupling of ATP synthesis with the reactions of the ETC is related to the
movement of protons (H+ ions) across the inner mitochondrial membrane
Complexes I, III and IV of ETC chain also serve as “proton pumps” to transfer
protons from the matrix side of the inner membrane to the intermembrane space
For every two electrons passed through ETC, four protons cross the inner
mitochondrial membrane through complex I, four through complex III and two more
though complex IV
This proton flow causes a buildup of H+ in the intermembrane space
The high [H+] in the intermembrane space becomes the basis for ATP synthesis
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Section 23.9
Oxidative Phosphorylation
•
•
•
•
•
The resulting concentration
difference (high in
intermembrane space than in
matrix) constitutes an
electrochemical (proton)
gradient which is always
associated with potential energy
The gradient build-up would
spontaneously push the H+ ions
through membrane-bound ATP
synthase
Proton flow is not through the
membrane itself since it is not
permeable to H+ ions
The proton flow through the
ATP synthetases powers the
synthesis of ATP
ATP synthetases are the
coupling factors in the ETC/OP
coupled reactions
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Section 23.10
ATP Production for the Common Metabolic Pathway
•
•
•
•
•
•
Formation of ATP accompanies
the flow of protons from the
intermembrane space back into
the mitochondrial matrix.
The proton flow results from an
electrochemical gradient across
the inner mitochondrial
membrane
For each mole of NADH
oxidized in the ETC, 2.5 moles
of ATP are formed.
For each mole of FADH2
Oxidized in the ETC, only 1.5
moles of ATP are formed.
For each mole of GTP
hydrolyzed one mole of ATP
are formed.
Ten molecules of ATP are
produced for each acetyl CoA
catabolized in the TCA
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Section 23.9
Oxidative Phosphorylation
Summary of the Common Metabolic Pathway
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Section 24.4
ATP Production for the Complete Oxidation of Glucose
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Section 24.4
ATP Production for the Complete Oxidation of Glucose
•
•
Cytosolic NADH produced
during Step 6 of Glycolysis
cannot directly participate in
the electron transport chain
because mitochondria are
impermeable to NADH and
NAD+
Glycerol 3-phosphatedihydroxyacetone phosphate
transport system shuttles
electrons from NADH, but
not NADH itself, across the
membrane:
– Dihydroxyacetone
phosphate and glycerol
phosphate freely cross
the mitochondrial
membrane
– The interconversion
shuttles the electrons
from NADH to FADH2
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Section 24.4
ATP Production for the Complete Oxidation of Glucose
• A total of 30 ATP molecules are produced in muscle and
nerve cells:
– 26 from oxidative phosphorylation / electron transport
chain coupled reactions
– 2 from oxidation of glucose to pyruvate
– 2 from conversion of GTP to ATP
• Aerobic oxidation of glucose is 15 times more efficient in
the ATP production as compared to anaerobic lactate
and ethanol processes
• In other cells such as heart and liver cells a more
complex shuttle system is used and 32 molecules are
produced instead of 30 per glucose molecule
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Section 23.11
The Importance of ATP
• The cycling of ATP and ADP in metabolic processes is
the principal medium for energy exchange in biochemical
processes
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Section 23.12
Non-ETC Oxygen-Consuming Reactions
• >90% of inhaled oxygen via respiration is consumed
during oxidative phosphorylation.
• Remaining O2 are converted to several highly reactive
oxygen species (ROS) with in the body.
• Examples of ROS:
–
–
–
–
Hydrogen peroxide (H2O2)
Superoxide ion (O2-) and
Hydroxyl radical (OH)
Superoxide ion and hydroxyl radicals have unpaired electron
and are extremely reactive
• ROS can also be formed due to external influences such
as polluted air, cigarette smoke, and radiation exposure
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Section 23.12
Non-ETC Oxygen-Consuming Reactions
• Reactive oxygen species (ROS) are both beneficial as
well a problematic within the body
• Beneficial Example: White blood cells produce a
significant amount of superoxide free radicals via the
following reaction to destroy the invading bacteria and
viruses.
– 2O2 + NADPH  2O2- + NADP+ + H+
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Section 23.12
Non-ETC Oxygen-Consuming Reactions
• > 95% of the ROS formed are quickly converted to non
toxic species :
2O2- + 2H+
2H2O2
Superoxide
dismutase
Catalase
H2O2 + O2
H2O + O2
• About 5% of ROS escape destruction by superoxide
dismutase and catalase enzymes.
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Section 23.12
Non-ETC Oxygen-Consuming Reactions
• Antioxidant molecules present in the body help trap ROS
species
• Antioxidants present in the body:
• Vitamin K
• Vitamin C
• Glutathione (GSH)
• Beta-carotene
• Plant products such as flavonoids are also good
antioxidants – Have shown promise in the management
of many disorders associated with ROS production
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Section 23.13
B Vitamins and the Common Metabolic Pathway
• Structurally modified B-vitamins function as coenzymes
in the metabolic pathways
• Four B Vitamins participate in various reactions:
– Niacin – NAD+ and NADH
– Riboflavin – as FAD, FADH2 and FMN
– Thiamin – as TPP
– Pantothenic acid - as CoA
• With out these B-vitamins body would be unable to
utilize carbohydrates, proteins and fats as energy
sources.
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Section 24.10
B-Vitamins and Carbohydrate Metabolism
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