Carbohydrate Metabolism Overview

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Big Picture in Focus: ULO3. Demonstrate understanding of

carbohydrate metabolic pathways and its intermediate compounds.
Metalanguage
The most essential terms and concepts below are defined, for you to have a better understanding of this
section in the course. You are advised to frequently refer to these definitions to help you understand the succeeding
topics.
1. Glycolysis – Glycolysis, a series of ten reactions that occur in the cytosol, it is a process in which one glucose
molecule is converted into two molecules of pyruvate. A net gain of two molecules of ATP and two molecules of
NADH results from the metabolizing of glucose to pyruvate.
2. Fates of pyruvate – With respect to energy-yielding metabolism, the pyruvate produced by glycolysis can be
converted to acetyl CoA under aerobic conditions or to lactate under anaerobic conditions. Some microorganisms
convert pyruvate to ethanol, an anaerobic process.
3. Glycogenesis – Glycogenesis is the process whereby excess glucose-6-phosphate is converted into glycogen. The
glycogen is stored in the liver and in muscle tissue.
4. Glycogenolysis – Glycogenolysis is the breakdown of glycogen into glucose-6-phosphate. This process occurs
when muscles need energy and when the liver is restoring a low blood-sugar level to normal.
5. Gluconeogenesis – Gluconeogenesis is the formation of glucose from pyruvate, lactate, and certain other
substances. This process takes place in the liver when glycogen supplies are being depleted and when carbohydrate
intake is low.
6. Cori cycle – The Cori cycle is a cyclic process involving the transport of lactate from muscle tissue to the liver, the
re-synthesis of glucose by gluconeogenesis, and the return of glucose to muscle tissue.
7. Pentose phosphate pathway – The pentose phosphate pathway metabolizes glucose to produce ribose (a
pentose), NADPH, and other sugars needed for biosynthesis.
8. Carbohydrate metabolism and hormones – Insulin decreases blood-glucose levels by promoting the uptake of
glucose by cells. Glucagon increases blood-glucose levels by promoting the conversion of glycogen to glucose.
Epinephrine stimulates the release of glucose from glycogen to muscle cells.
Essential Knowledge
Metabolism
• Sum total of all chemical reactions in a living organism.
• The various chemical processes by which food is utilized by a living organism to provide energy, growth
substance, and cell repair.
• Metabolism will provide the source of energy we need for all our activities such as thinking, moving,
breathing, walking, talking, etc.
Reference textbook: Stoker, H. S. (2017). Biochemistry 3rd Edition. C & E Publishing Inc. Quezon City. 1
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• Energy is also needed for many of the cellular processes such as protein synthesis, DNA replication, RNA
transcription and transport across the membrane, etc.
Catabolism and Anabolism

• Catabolism: All metabolic reactions in which large biochemical molecules are broken down to smaller ones.
– Usually energy is released in these reactions.
– Example: Oxidation of glucose.
• Anabolism: All metabolic reactions in which small biochemical molecules are joined to form larger ones.
– Usually require energy.
– Example: The synthesis of proteins.
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Metabolic Pathway
• Series of consecutive biochemical reactions used to convert a starting material into an end product.
• There are two types of metabolic pathways:
– Linear
– Cyclic
• The major pathways for all forms of life are similar:
Metabolism and Cell Structure
Eukaryotic Cell Organelles and Their Function

• Nucleus: DNA replication and RNA synthesis.
• Plasma membrane: Cellular boundary.
• Cytoplasm: The water-based material of a eukaryotic cell.
• Mitochondria: Generates most of the energy needed for cell.
• Lysosome: Contain hydrolytic enzymes needed for cell rebuilding, repair and degradation.
• Ribosome: Sites for protein synthesis.
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Mitochondria
• An organelle that is responsible for the generation of most of the energy for a cell:
– Outer membrane: Permeable to small molecules: 50% lipid, 50% protein.
– Inner membrane: Highly impermeable to most substances: 20% lipid, 80% protein.
– Inner membrane folded into cristae to increase surface area.
– Synthesis of ATP occurs on the inner membrane.
Important Nucleotide-Containing Compounds in Metabolic Pathways
High-energy Phosphate Compounds

• Several phosphate containing compounds found in metabolic pathways are known as high energy
compounds.
• High energy compounds have greater free energy of hydrolysis than a typical compound:
– They contain at least one reactive bond -- called strained bond.
– Energy to break these bonds is less than a normal bond -- hydrolysis of high energy compounds give
more energy than normal compounds.
– More negative the free energy of hydrolysis, greater the bond strain.
– Typically the free energy release is greater than 6.0 kcal/mole (indicative of bond strain).
– Strained bonds are represented by sign ~ (squiggle bond).
Adenosine Phosphates (ATP, ADP and AMP)

• AMP: Structural component of RNA.
• ADP and ATP: Key components of metabolic pathways.
– Phosphate groups are connected to AMP by strained bonds which require less than normal energy to
hydrolyze them.
ATP + H2O → ADP + PO43- + Energy
ADP + H2O → AMP + PO43- + Energy
• Overall Reaction: ATP + 2H2O → AMP + 2 PO43- + Energy
• The net energy produced in these reactions is used for cellular reactions.
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Flavin Adenine Dinucleotide (FAD)

• A coenzyme required in numerous metabolic redox reactions.
• FAD is oxidized form.
• FADH2 is reduced form.
• In enzyme reactions FAD goes back and forth (equilibrium) from oxidized to reduced form.
• A typical cellular reaction in which FAD serves as oxidizing agent involves conversion of an alkane to an
alkene.
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Nicotinamide Adenine Dinucleotide (NAD)

• NAD+: coenzyme
• NADH is reduced form.
• 3 Subunit structure:
– Nicotinamide - ribose - ADP
• 6 Subunit structure:
– Nicotinamide - ribose - phosphate - phosphate - ribose - adenine
• A typical cellular reaction in which NAD+ serves as the oxidizing agent is the oxidation of a secondary
alcohol to give a ketone.
Coenzyme A
• A derivative of vitamin B.
• Active form of coenzyme A is the sulfhydryl group (-SH group) in the ethanethiol subunit of the coenzyme.
• Acetyl-CoA (acetylated)
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Classification of Metabolic Intermediate Compounds

• Metabolic intermediate compounds can be classified into three groups based on their functions.
An Overview of Biochemical Energy Production

• Energy needed to run human body is obtained from food.
• Multi-step process that involves several different catabolic pathways aid in this process.
• There are four general stages in the biochemical energy production process:
– Stage 1: Digestion
– Stage 2: Acetyl group formation,
– Stage 3: Citric acid cycle
– Stage 4: Electron transport chain and Oxidative phosphorylation
• Each stage also involves numerous reactions.
Stage 1. Digestion
• Begins in mouth (saliva contains starch digesting enzymes), continues in the stomach (gastric juice),
completed in small intestine:
– Results in small molecules that can cross intestinal membrane into the blood.
• End Products of digestion:
– Glucose and monosaccharides from carbohydrates.
– Amino acids from proteins.
– Fatty acids and glycerol from fats and oils.
• The digestion products are absorbed into the blood and transported to body’s cells.
Stage 2. Acetyl Group Formation

• The small molecules from Stage 1 are further oxidized.
• End product of these oxidations is acetyl CoA.
• Primary products include two-carbon acetyl units (which become attached to coenzyme A to give acetyl
CoA) and the reduced coenzyme NADH.
• Involves numerous reactions:
– Reactions occur both in cytosol (glucose metabolism) as well as mitochondria (fatty acid metabolism)
of the cells.
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Stage 3. Citric Acid Cycle

• Takes place inside the mitochondria.
• In this stage acetyl group is oxidized to produce CO2 (which we exhale during breathing) and energy.
• Most energy is trapped and carried by the reduced coenzymes NADH and FADH 2 to the fourth stage.
• Some energy produced in this stage is lost in the form of heat.
Stage 4. Electron Transport Chain and Oxidative Phosphorylation

• Takes place in mitochondria.
• NADH and FADH2 are oxidized to release H+ and electrons.
• H+ are transported to the inter-membrane space in mitochondria.
• Electrons are transferred to O 2 and O2 is reduced to H2O.
• H+ ions reenter the mitochondrial matrix and drive ATP-synthase reaction to produce ATP.
• ATP is the primary energy carrier in metabolic pathways.
• The reactions in stages 3 & 4 are common to the processing of carbohydrates, fats, and proteins.
• Collectively known as the common metabolic pathways, i.e., the sum of the reactions that occur in the
citric acid cycle, the electron transport chain, and the oxidative phosphorylation.
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Chemical Processes Prior to Metabolism
A. Digestion
• Breakdown of food molecules by hydrolysis into simpler chemical units that can be used by cells in
metabolic processes.
B. Absorption
• The process of getting the digested molecules into the bloodstream and ultimately into the cells where
metabolism occurs.
• Takes place in the small intestine through tiny, finger-like projections, called villi, that line the inner surface.
• Each villus is richly supplied with a fine network of blood vessels and a central lymph vessel.
Carbohydrate Metabolism
Digestion and Absorption of Carbohydrates
• Carbohydrate digestion: Begins in the mouth

– Salivary enzyme“α-amylase”catalyzes the hydrolysis of α-glycosidic 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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• 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.
• 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:
– oxidized to CO2 and H2O (ATP)
– converted to fat
– converted to muscle glycogen
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• Blood-sugar level:
– 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.
– Abnormal conditions:
A. Hypoglycemia
– 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 heartbeat,
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.
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.
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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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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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.
Gluconeogenesis
• Metabolic pathway by which glucose is synthesized from non-carbohydrate 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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The Pentose Phosphate Pathway / Hexose monophosphate shunt

• Initial reactant of the pathway is glucose-6-phosphate.
• 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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Glycolysis
• A series of reactions in the cytoplasm which converts glucose (C6) to two molecules of pyruvate (a C 3
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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• 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 3-phosphate
– Enzyme: Triosephosphate isomerase
• Step 6: Formation of 1,3-bisphosphoglycerate

– Glyceraldehyde 3-phosphate is oxidized and phosphorylated
– Enzyme: Glyceraldehyde-3-phosphate dehydrogenase
• 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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• 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 alcoholic 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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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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Terminology For Glucose Metabolic Pathways
Relationships Among Four Common Metabolic Pathways That Involve Glucose
ATP Production and Consumption

• There is a net gain of two ATP molecules in glycolysis for every glucose molecule processed
• Overall equation for glycolysis
Glucose + 2NAD+ 2 Pyruvate + 2NADH + 2H+ + 2H2O
2ADP + 2Pi 2ATP
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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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• 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 Alpha- Ketoglutarate 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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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.
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.
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 re-oxidized, ultimately
by O2.
• 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 I: NADH-coenzyme Q reductase
– Complex II: Succinate-coenzyme Q reductase
– Complex III: Coenzyme Q - cytochrome C reductase
– Complex IV: Cytochrome C oxidase
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• Two mobile electron carriers are:

– Coenzyme Q and cytochrome c.
Complex I: NADH- Coenzyme Q Reductase

• Facilitates transfer of electrons from NADH to coenzyme Q.
Complex II: Succinate-Coenzyme 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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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
Summary of the flow of electrons through four complexes of the electron transport chain.
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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.
• 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.
• 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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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.
Summary of the Common Metabolic Pathway
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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-phosphate-dihydroxyacetone 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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• 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.
The Importance of ATP

• The cycling of ATP and ADP in metabolic processes is the principal medium for energy exchange in
biochemical processes.
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.
• 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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• > 95% of the ROS formed are quickly converted to non-toxic species:
• About 5% of ROS escape destruction by superoxide dismutase and catalase enzymes.

• 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.
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
• Without these B-vitamins body would be unable to utilize carbohydrates, proteins and fats as energy
sources.
B-Vitamins and Carbohydrate Metabolism
-END-
GOOD JOB!
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Keywords Index
Metabolism Insulin Glycolysis Aerobic Process
Salivary amylase Glucagon Citric Acid Cycle Kreb’s Cycle
Maltase Epinephrine Glucose Cori Cycle
Sucrase Adrenaline Pyruvate Acetyl CoA
Lactase Glycogenesis Lactate Ethanol
Hypoglycemia Glycogenolysis Glycerol ATP
Hyperglycemia Gluconeogenesis Anaerobic Process NADH
FADH2 ADP Electron Transport Chain Coenzyme
Oxidative Phosphorylation Metabolic Pathway Oxidation GTP
Shuttle System Antioxidants TPP Succinyl CoA

Carbohydrate Metabolism Overview

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Carbohydrate Metabolism Overview

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College of Health Sciences Education

3rd Floor, DPT Building

Big Picture in Focus: ULO3. Demonstrate understanding of

Catabolism and Anabolism

Metabolism and Cell Structure

Eukaryotic Cell Organelles and Their Function

Important Nucleotide-Containing Compounds in Metabolic Pathways

High-energy Phosphate Compounds

Adenosine Phosphates (ATP, ADP and AMP)

Flavin Adenine Dinucleotide (FAD)

Nicotinamide Adenine Dinucleotide (NAD)

Classification of Metabolic Intermediate Compounds

An Overview of Biochemical Energy Production

Stage 2. Acetyl Group Formation

Stage 3. Citric Acid Cycle

Stage 4. Electron Transport Chain and Oxidative Phosphorylation

Chemical Processes Prior to Metabolism

• Carbohydrate digestion: Begins in the mouth

• In stomach very little carbohydrate is digested:

Hormonal Control of Carbohydrate Metabolism

Epinephrine (also called Adrenaline)

• There are six major metabolic pathways of glucose:

Glycogen Synthesis and Degradation

Glycogenesis and Glycogenolysis

The Pentose Phosphate Pathway / Hexose monophosphate shunt

• Step 1: Formation of glucose-6-phosphate:

• Step 2: Formation of Fructose-6-phosphate:

• Step 3: Formation of Fructose 1,6-bisphosphate:

• Step 4: Formation of Triose Phosphates:

• Step 5: Isomerization of Triose Phosphates

• Step 6: Formation of 1,3-bisphosphoglycerate

• Step 7: Formation of 3-bisphosphoglycerate

• Step 8: Formation of 2-phosphoglycerate

• Step 9: Formation of Phosphoenolpyruvate:

• Step 10: Formation of Pyruvate:

The Cori Cycle

Terminology For Glucose Metabolic Pathways

Relationships Among Four Common Metabolic Pathways That Involve Glucose

ATP Production and Consumption

• Overall equation for glycolysis

Glucose + 2NAD+ 2 Pyruvate + 2NADH + 2H+ + 2H2O

2ADP + 2Pi 2ATP

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

• Step 4: Oxidation of Alpha- Ketoglutarate and Formation of CO2

• Step 6: Oxidation of Succinate

• Step 7: Hydration of Fumarate

• Step 8: Oxidation of L-Malate to regenerate Oxaloacetate

Important Features of the Cycle

Regulation of the Citric Acid Cycle

The Electron Transport Chain

• Two mobile electron carriers are:

Complex I: NADH- Coenzyme Q Reductase

Complex II: Succinate-Coenzyme Q Reductase

Complex III: Coenzyme Q – Cytochrome c Reductase

Complex IV: Coenzyme Q – Cytochrome c Reductase

ATP Production for the Common Metabolic Pathway

Summary of the Common Metabolic Pathway

ATP Production for the Complete Oxidation of Glucose

• A total of 30 ATP molecules are produced in muscle and nerve cells:

The Importance of ATP