BIOCHEMICAL ENERGY

PRODUCTION
METABOLISM

Is the sum total of all the biochemical reactions that take place in a living organism.
Metabolic Reactions fall into 2 types:
1. Catabolism – All metabolic reactions in which large biomolecules are broken down
to smaller ones. Release energy.
Ex. Hydrolysis of a polysaccharide to monosaccharides
2. Anabolism – All metabolic reactions in which small biochemical molecules are joined
together to form larger ones. Requires energy.
Ex. Synthesis of a polysaccharide from monosaccharides
CLASSIFY EACH OF THE FOLLOWING CHEMICAL
PROCESSES AS CATABOLIC OR ANABOLIC

• 1. Formation of nucleic acid from nucleotides

• 2. Hydrolysis of a TAG to glycerol and fatty acids

• 3. Formation of a TAG from glycerol and fatty acids
• 4. Formation of a nucleotide from phosphate, N base and pentose sugar
• 5. Synthesis of proteins from amino acids.
METABOLISM AND CELL STRUCTURE

• Cells are of two types:

• Prokaryotic cells – have no nucleus and are found only in bacteria.
• Eukaryotic cells – a cell in which the DNA is found in a membrane
enclosed nucleus. The type present in humans.
• Components of the cell that are of importance in our study:
• 1. Cytoplasm – water based material of a E cell that lies between the
nucleus and the outer membrane of the cell.
• 2. Organelles – small structures within the cytoplasm of a cell that carries out a specific
cellular functions.
• 3. Cytosol – the water based fluid parts of the cytoplasm of a cell and the organelles are
surrounded by this fluid.
Three important types of organelles:
1. Ribosomes – sites where protein synthesis occurs.
2. Lysosomes – an organelles that contain hydrolytic enzymes needed for cellular
rebuilding, repair, and degradation. Some lysosomes hydrolyze proteins to amino acids.
MITOCHONDRION

• 3. Mitochondrion – is an organelle that is responsible for the generation of most

of the energy for a cell.
• - A sausage shaped organelles containing both an outer membrane and a
multifolded inner membrane.
• Outer membrane – which is about 50% lipid and 50% protein, is freely
permeable to small molecules.
• Inner membrane – which is about 20% lipid and 80% protein and is highly
permeable to most substances.
MITOCHONDRION

• The nonpermeable nature of the inner membrane divides a

mitochondrion into two separate components:
• Matrix – the interior region
• Intermembrane space – the region between the inner and outer
membrane
• Cristae – the folds of the inner membrane that protrude into the matrix.
• ATP synthase complex – a small spherical knobs attached to the cristae.
• This small spherical small knobs are located on the matrix side of the
inner membrane, are responsible for ATP synthesis.
 MITOCHONDRIA

• The mitochondrion is the powerhouse of the cell. It is the organelle where many of the reactions
of the common catabolic pathway occur. It consists of an outer membrane, which surrounds a
inner membrane.
– The folds of the inner membrane are called cristae.
– The space that surrounds them is the matrix.
• The enzymes for ATP synthesis (electron transport and oxidative phosphorylation) are located on
the cristae. The enzymes for the citric acid cycle are found within the matrix, near the surface of the
inner membrane.
IMPORTANT INTERMEDIATE COMPOUNDS IN
METABOLIC PATHWAYS
• 1. Adenosine Phosphates ( ATP, ADP and AMP)

• 2. Flavin Adenine Dinucleotide (FAD, FADH2)

• 3. Nicotinamide Adenine Dinucleotide (NAD+, NADH)
• 4. Coenzyme A (CoA –SH)
 ATP AS PRIMARY ENERGY CARRIER
• Adenosine triphosphate, ATP, consists of:
– the heterocyclic base adenine
– the sugar ribose
– a triphosphate group
• At physiological pH, the protons on the triphosphate group are removed, giving ATP a charge of -4.
– In the cell, it is complexed with Mg2+ in a 1:1 ratio, giving it a net charge of -2.
 HYDROLYSIS OF ATP

• The triphosphate group is the part of the molecule that is important in the transfer of
biochemical energy. The key reaction is the transfer of a phosphoryl group, —PO3 2- , from ATP to
another molecule.
– During the hydrolysis of ATP in water, a phosphoryl group is transferred from ATP to a water
molecule:

– The products are adenosine diphosphate (ADP) and a phosphate ion, often referred to as an
inorganic phosphate, Pi , or just phosphate.
 ATP AS PRIMARY ENERGY CARRIER
• Adenosine triphosphate, ATP, consists of:
– the heterocyclic base adenine
– the sugar ribose
– a triphosphate group
• At physiological pH, the protons on the triphosphate group are removed, giving ATP a charge of -4.
– In the cell, it is complexed with Mg2+ in a 1:1 ratio, giving it a net charge of -2.
 HYDROLYSIS OF ATP

• The triphosphate group is the part of the molecule that is important in the transfer of
biochemical energy. The key reaction is the transfer of a phosphoryl group, —PO3 2- , from ATP to
another molecule.
– During the hydrolysis of ATP in water, a phosphoryl group is transferred from ATP to a water
molecule:

– The products are adenosine diphosphate (ADP) and a phosphate ion, often referred to as an
inorganic phosphate, Pi , or just phosphate.
HYDROLYSIS OF ATP

• The transfer of a phosphoryl group from ATP to water is accompanied by a release of

energy.
• Free energy, ΔG, is used as a measure of the energy change.
– When energy is released, ΔG is negative.
– When energy is absorbed, ΔG is positive.
– When ΔG is measured under standard conditions, it is represented by ΔG o.
– When ΔG o is measured under body conditions, it is represented by ΔG o’.
HYDROLYSIS OF ATP

• The liberated free energy is available for use by the cell to carry out processes requiring
an input of energy:
• ATP + H2O → ADP + Pi + H+ , ΔG o’= -7.3 kcal/mol
• Other phosphate-containing compounds also liberate energy on hydrolysis:
HYDROLYSIS OF ATP

• Compounds that liberate a large amount of free energy on hydrolysis are called high-
energy compounds.
• The hydrolysis of ATP to ADP is the principal energy-releasing reaction for ATP. Some
other hydrolysis reaction occur under some conditions, such as the hydrolysis of ATP to
adenosine monophosphate, AMP, and pyrophosphate, PPi :
HYDROLYSIS OF ATP

• This is usually followed by immediate hydrolysis of the pyrophosphate, which releases

even more energy:

• The hydrolyses of ATP and related compounds are summarized below:

 ATP-ADP CYCLE

• ATP functions as an immediate donor of free energy rather than

as an energy storage medium.
– The turnover rate of ATP is very high: typically, an ATP molecule
is hydrolyzed within 1 minute after its formation.
– At rest, a human body hydrolyzes ATP at the rate of about 40 kg
every 24 hours.
– During strenuous exertion, this rate may be as high as 0.5 kg
per minute.
• ATP must be continuously regenerated from ADP if cellular
work is to occur.
FLAVIN ADENINE DINUCLEOTIDE (FAD)

• Flavin adenine dinucleotide (FAD) is another major electron carrier. It is a derivative of

ADP and the vitamin riboflavin.
FLAVIN ADENINE DINUCLEOTIDE (FAD)

• The active site is located within the riboflavin ring system. Unlike NAD+ , FAD accepts
both of the hydrogen atoms lost by the substrate, forming the reduced species FADH2
FLAVIN ADENINE DINUCLEOTIDE (FAD)

• The substrates for reactions involving FAD are often those in which a —CH2—CH2—
portion of the substrate is oxidized to a double bond:
 NICOTINAMIDE ADENINE DINUCLEOTIDE (NAD+ )

• Nicotinamide adenine dinucleotide (NAD+ ),

is an electron transporter which is a
derivative of ADP and the vitamin
nicotinamide (B3 ).
NICOTINAMIDE ADENINE DINUCLEOTIDE (NAD+ )

• The reactive site of NAD+ is in the nicotinamide portion. – When oxidizing a substrate,
the nicotinamide ring accepts two electrons and one proton, forming the reduced
coenzyme NADH:
NICOTINAMIDE ADENINE DINUCLEOTIDE (NAD+ )

• A typical cellular reaction in which NAD+ serves as an electron acceptor is the oxidation of an alcohol:

• • In this reaction, one hydrogen atom of the alcohol substrate is directly transferred to NAD+ , whereas
the other appears in solution as H+ . Both electrons lost by the alcohol have been transferred to the
nicotinamide ring in NADH.
NICOTINAMIDE ADENINE DINUCLEOTIDE (NAD+ )

• Biochemical reactions involving coenzymes are often written more concisely:

– This notation emphasizes the oxidation reaction and the involvement of the coenzyme.
COENZYMES

• Coenzymes are weakly-bound organic groups that participate in enzyme-catalyzed

reactions, often by acting as shuttle systems for the transfer of chemical groups (e.g.,
hydrogen transport). Many important coenzymes are formed from vitamins.
• Coenzyme A is a central compound in metabolism. It is part of acetyl coenzyme A (acetyl
CoA), the substance formed from all foods as they pass through Stage II of catabolism.
COENZYME A

• Components of coenzyme A:
– vitamin B5 , pantothenic acid, in the center.
– a phosphate derivative of ADP
– b-mercaptoethylamine, which puts a reactive sulfhydryl group (—SH) at the end of the
molecule (CoA—SH).
COENZYME A

• The letter A is included in the name Coenzyme A to signify its participation in the
transfer of acetyl groups, but Coenzyme A transfers all acyl groups. This is important in
fatty acid oxidation and synthesis.

• Acyl groups are linked to coenzyme A through the sulfur atom in a thioester bond:
 ELECTRON TRANSPORTERS

• Most of energy for ATP synthesis is released when the oxygen we breathe is reduced.
– Oxygen accepts electrons and H+ , producing water.
– The electrons come from the oxidation of fuel molecules, but are are not
transferred directly to the oxygen.
– These substrates first transfer the electrons to special coenzyme carriers.
• The reduced forms of these coenzymes transfer the electrons to oxygen through the reactions of
the electron transport chain.
• ATP is formed from ADP and Pi as a result of this flow of electrons.
33 OVERVIEW OF THE BIOCHEMICAL ENERGY
PRODUCTION
• Energy needed to run human body is obtained from food
• Multi-step process that involves several different catabolic pathways
• 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
• Involves numerous reactions:
• Reactions occur both in cytosol (glucose metabolism) as well
as mitochondria (fatty acid metabolism) of the cells.
STAGE 3. CITRIC ACID CYCLE

• Takes place in inside the mitochondria

• First intermediate of the cycle is citric acid – therefore
designated as Citric acid cycle
• In this stage acetyl group is oxidized to produce CO2 and
energy
• The carbon oxide we exhale comes primarily from this stage
• Most energy is trapped in reduced coenzymes NADH and
FADH2
• Some energy produced in this stage is lost in the form of heat
STAGE 3 : CITRIC ACID CYCLE

• Stage 3 in the oxidation of fuel molecules begins when the two-carbon acetyl units of
acetyl CoA enter the citric acid cycle.

– The citric acid cycle is also known as the tricarboxylic acid cycle (TCA cycle) because of
the three carboxylic acid groups in citric acid, and the Krebs cycle after Hans A. Krebs, who
deduced the reaction sequence in 1937.
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 O2 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
CATABOLISM OF FOOD

• The catabolism of food is a three stage process.

• Stage I: The digestion of large, complex molecules into simpler ones. – The most common
reaction in digestion is hydrolysis:
CATABOLISM OF FOOD

• Stage II: The small molecules from digestion are broken down into even simpler units,
usually the two-carbon acetyl portion of acetyl coenzyme A (acetyl CoA):

– Some energy is produced at this stage, but much more is produced during the oxidation
of the acetyl units in Stage III.
 CATABOLISM OF FOOD

• Stage III: This is referred to as the common catabolic pathway because the reactions are the same
regardless of the type of food being degraded.
– citric acid cycle
– electron transport
– oxidative phosphorylation
• Energy released in Stage III appears in the form of energy-rich molecules of ATP.
– The whole purpose of the catabolic pathway is to convert the chemical energy in foods
into molecules of ATP, which carries energy to parts of the cell where energy is needed.
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 the reduced coenzymes FADH2 and
NADH are produced
• Also know as tricarboxylic acid cycle (TCA) or Krebs cycle:
• Citric acid is a tricarboxylic acid – TCA cycle
• Named after Hans Krebs who elucidated this pathway

• Two important types of reactions:

• Oxidation 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

• Summary of citric acid cycle reactions:

Acetyl CoA + 3NAD+ + FAD + GDP + Pi + 2H2O → 2CO2 + CoA-SH + 3NADH + 2H+ + FADH2 + GTP
REACTIONS OF 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 Alpha-Ketoglutarate and Formation of CO2
• Step 5: Thioester bond cleavage in Succinyl CoA and Phosphorylation of GDP
• Step 6: Oxidation of Succinate
• Step 7: Hydration of Fumarate
• Step 8: Oxidation of L-Malate to Regenerate Oxaloacetate
 CITRIC ACID CYCLE

• The reactions of the citric acid cycle can be added to give the net equation:
• acetyl CoA + 3NAD+ + FAD + GDP + Pi + 2H2O → 2CO2 + CoA-S-H + 3NADH + 2H+ +
FADH2 + GTP
• Some important features of the citric acid cycle:
1. Acetyl CoA is the fuel of the citric acid cycle.
2. The operation of the cycle requires a supply of the oxidizing agents NAD+ and FAD from the
electron transport chain.
– Because oxygen is the final acceptor of electrons in the electron transport chain, the
continued operation of the cycle depends ultimately on an adequate supply of oxygen.
 CITRIC ACID CYCLE

3. Two carbon atoms enter the cycle as an acetyl unit, and two carbon atoms leave the cycle as two
molecules of CO2 . However, the carbon atoms leaving the cycle correspond to carbon atoms that
entered in the previous cycle; there is a one-cycle delay between the entry of two carbon atoms as
an acetyl unit and their release as CO2 .
4. In each complete cycle, four oxidation-reduction reactions produce three molecules of NADH
(Steps 3, 4, and 8) and one molecule of FADH2 (Step 6).
5. One molecule of the high-energy phosphate compound guanosine triphosphate (GTP) is
generated (Step 5).
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, ADP activates citrate synthase
• Similarly ADP and NADH control isocitrate dehydrogenase:
• NADH acts as an inhibitor
• ADP as an activator.
REGULATION OF THE CITRIC ACID CYCLE

• The rate at which the citric acid cycle operates is precisely adjusted to meet cellular
needs for ATP. – Citrate synthetase (Step 1) is an allosteric enzyme that is inhibited by
ATP and NADH and activated by ADP. – Isocitrate dehydrogenase (Step 3) is an allosteric
enzyme that is inhibited by NADH and activated by ADP. – The a-ketoglutarate
dehydrogenase complex (Step 4) is a group of allosteric enzymes that is inhibited by
succinyl CoA, NADH, the products of the reaction that it catalyzes, and ATP.
• The rate at which the citric acid cycle operates is reduced when cellular ATP levels are
high, and stimulated when ATP supplies are low (and ADP levels are high).
CITRIC ACID CYCLE

• A two-carbon acetyl group enters the cycle (Step 1) and two carbon atoms are liberated
as CO2 molecules (Steps 3 and 4) • This series of reactions begins and ends with a C4
compound, oxaloacetate (hence the term cycle).

• In each trip around the cycle, the starting material is regenerated and the reactions can
proceed again as long as there is more acetyl CoA available as fuel.
 CITRIC ACID CYCLE

• The reactions of the citric acid cycle can be added to give the net equation:
• acetyl CoA + 3NAD+ + FAD + GDP + Pi + 2H2O → 2CO2 + CoA-S-H + 3NADH + 2H+ +
FADH2 + GTP
• Some important features of the citric acid cycle:
1. Acetyl CoA is the fuel of the citric acid cycle.
2. The operation of the cycle requires a supply of the oxidizing agents NAD+ and FAD from the
electron transport chain.
– Because oxygen is the final acceptor of electrons in the electron transport chain, the
continued operation of the cycle depends ultimately on an adequate supply of oxygen.
CITRIC ACID CYCLE

• The citric acid cycle is the principal process for generating the reduced coenzymes
NADH and FADH2 , which are necessary for the reduction of oxygen and ATP synthesis in
the electron transport chain. – The citric acid cycle also functions as a source of
intermediates for biosynthesis of other important molecules (e.g., some amino acids).
• The reactions of the citric acid cycle occur within the matrix of the mitochondria.
• There are eight reactions in the cycle. Of particular importance are the reactions where
NADH (Steps 3, 4, and 8) and FADH2 (Step 6) are produced.
 ELECTRON TRANSPORT CHAIN

• The reduced coenzymes NADH and FADH2 are end products of the citric acid cycle.
• In the final stage of food oxidation, the hydrogen ions and electrons carried by these coenzymes
combine with oxygen to form water:
4H+ + 4e− + O2 → 2H2O

– This series of reactions is called the electron transport chain. It involves a number of enzymes and
cofactors located within the inner membrane of the mitochondria.
– Electrons from the reduced coenzymes are passed from one electron carrier to another within
the membrane in assembly-line fashion, until they are combined with the final electron acceptor, O2 .
 ELECTRON TRANSPORT CHAIN
• The electron transport chain is found in the inner membrane of the mitochondria.
• A summary of the reactions of the ETC:
– The first electron carrier is an enzyme similar to FAD called flavin mononucleotide (FMN).
– Two electrons and one H+ from NADH pass to FMN, then to an iron-sulfur protein, and then to
coenzyme Q (CoQ).
ENERGY CHANGES IN THE ELECTRON TRANSPORT
CHAIN
• Thus, over the entire catabolic pathway (citric acid cycle, electron transport chain, and
oxidative phosphorylation), 10 ATP molecules are formed per molecule of acetyl CoA
catabolized:
ENERGY CHANGES IN THE ELECTRON TRANSPORT
CHAIN
• During oxidative phosphorylation:
– the conversion of NADH to NAD+ generates 2.5 molecules of ATP from ADP.
– the conversion of FADH2 to FAD generates 1.5 molecules of ATP.
• Every molecule of acetyl CoA entering the citric acid cycle produces:
– 3 molecules of NADH
– 1 molecule of FADH2
– GTP (equivalent to ATP)
ENERGY CHANGES IN THE ELECTRON TRANSPORT
CHAIN
OXIDATIVE PHOSPHORYLATION

• As electrons move along the electron transport chain, about 52.6 kcal/mol of free energy
is released.
• Some of this energy is conserved by the synthesis of ATP from ADP and Pi . Because this
synthesis of ATP (a phosphorylation reaction) is linked to the oxidation of NADH and
FADH2 , it is called oxidative phosphorylation. It takes place at three different locations
along the electron transport chain (see next slide).
• A summary of the reactions of the ETC, cont.:
– Four of the five remaining electron carriers are cytochromes (cyt), which are iron-
containing enzymes.
– In the final step, an oxygen atom accepts the elctrons and combines with two H+ ions to
form water.
• A summary of the reactions of the ETC, cont.:
– CoQ is also the entry point for the two electrons and two H+ ions from FADH2 . As
NADH and FADH2 release their H+ and electrons, NAD+ and FAD are regenerated for
reuse in the citric acid cycle.
• 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 ultimately receiver of electrons is molecular oxygen
• The electron transport (respiratory chain) gets its name from
the fact electrons are transported to oxygen absorbed via
respiration
• The overall ETC reaction: 2 H+ + 2e- + 1/2 O2 → H2O + energy
• Energy is used to synthesize ATP in oxidative phosphorylation
• Note that 2 hydrogen ions, 2 electrons, and one half-oxygen molecule react to
form the product water
• This relatively straight forward reaction actually requires eight or more steps
• The reaction releases energy (exothermic reaction)
• The energy released is coupled with the formation of three ATP molecules per
every molecule of NADH processed through ETC
• 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.
COMPLEX 1: NADH-COENZYME Q REDUCTASE

• NADH from citric acid cycle is the source of electrons for this complex
• It contains >40 subunits including flavin mononucleotide (FMN) and
several iron-sulfur protein clusters (FeSP)
• Net result: Facilitates transfer of electrons from NADH to coenzyme Q
• Several intermediate reactions are involved in this electron transfer
COMPLEX II: SUCCINATE-COENZYME Q REDUCTASE

• Smaller than complex I

• Contains only four subunits including two iron-sulfur protein clusters (FeSP)
• Succinate is converted to fumarate by this complex
• In the process it generates FADH2
• CoQ is the final recipient of the electrons from FADH2
COMPLEX III: COENZYME Q – CYTOCHROM C
REDUCTASE
• Complex III contains 11 different subunits
• 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
• Various cytochromes, e.g., cyt a, cyt b, cyt c, differ from each other by:
• Their protein constituents
• The manner in which the heme is bonded to the protein
• Attachments to the heme ring
COMPLEX IV: CYTOCHROME C OXIDASE

• Contains 13 subunits including two cytochromes

• 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
• It is estimated that 95 % of the oxygen used by cells serves as the final
electron acceptor for the ETC
NON ETC OXYGEN-CONSUMING RXNS

• >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
NON ETC OXYGEN-CONSUMING RXNS

• 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+

• > 95% of the ROS formed are quickly converted to non toxic species in the following
reactions:
NON ETC OXYGEN-CONSUMING RXNS

• > 95% of the ROS formed are quickly converted to non toxic species in the following
reactions:

• About 5% of ROS escape destruction by superoxide dismutase and catalase enzymes.

ANTIOXIDANT MOLECULES

• Antioxidant molecules present in the body help trap ROS species

• Antioxidants present in the body:
• Vitamin K
• Vitamin C
• Glutathione (GSH)
• Beta-carotine

• Plant products such as flavonoids are also good antioxidants – Have shown promise in
the management of many disorders associated with ROS production
THANK YOU!
Carbohydrate
Metabolism
 DIGESTION AND
ABSORPTION OF
CARBOHYDRATES

Digestion is the
biochemical process by
which food molecules,
through hydrolysis, are
broken down into
simpler chemical units
that can be used by
cells for their metabolic
needs.
 Glycolysis is the metabolic pathway by which
glucose (a C6 molecule) is converted into two
molecules of pyruvate (a C3 molecule), chemical
energy in the form of ATP is produced, and NADH-
reduced coenzymes are produced
GLYCOLYSIS • Anaerobic pathways- metabolic pathways in
which molecular oxygen is not a participant
• Aerobic pathways- pathways that require
molecular oxygen
Six-Carbon
Stage of
Glycolysis
(Steps 1–3)

• Step 1: Phosphorylation: Formation of Glucose 6-Phosphate. Glycolysis

begins with the phosphorylation of glucose to yield glucose 6-
phosphate.
Six-Carbon
Stage of
Glycolysis
(Steps 1–3)

• Step 2: Isomerization: Formation of Fructose 6-Phosphate

Six-Carbon
Stage of
Glycolysis
(Steps 1–3)

• Step 3. Phosphorylation: Formation of Fructose 1,6-Bisphosphate. This

step, like Step 1, is a phosphorylation reaction and therefore requires
the expenditure of energy.
 Three-
Carbon Stage
of Glycolysis
(Steps 4–10)

• Step 4: Cleavage: Formation of Two Triose Phosphates. In this

step, the reacting C6 species is split into two C3 (triose) species.
• Because fructose 1,6-bisphosphate, the molecule being split, is
unsymmetrical, the two trioses produced are not identical. One
product is dihydroxyacetone phosphate, and the other is
glyceraldehyde 3-phosphate.
 Three-
Carbon Stage
of Glycolysis
(Steps 4–10)

• Isomerization: Formation of Glyceraldehyde 3-Phosphate.

 • Step 6: Oxidation and Phosphorylation: Formation of 1,3
Bisphosphoglycerate. Phosphate group is added to glyceraldehyde 3-
Three-Carbon Stage of phosphate to produce 1,3-bisphosphoglycerate.
Glycolysis (Steps 4–10) • The newly added phosphate group in 1,3-bisphosphoglycerate is a high-
energy phosphate group. A high-energy phosphate group is produced
when a phosphate group is attached to a carbon atom that is also
participating in a carbon–carbon or carbon–oxygen double bond.
Three-Carbon Stage of Glycolysis (Steps 4–10)
• Step 7: Phosphorylation of ADP:
Formation of 3-
Phosphoglycerate. The
diphosphate species just formed
is converted back to a
monophosphate species.
• ATP production in this step
involves substrate-level
phosphorylation.
• Substrate-level phosphorylation
is the biochemical process by
which a high energy phosphate
group from an intermediate
compound (substrate) is directly
transferred to ADP to produce
ATP.
Three-Carbon Stage of Glycolysis (Steps 4–10)

• Step 8: Isomerization: Formation of 2-

Phosphoglycerate. In this isomerization step, the
phosphate group of 3-phosphoglycerate is moved
from carbon 3 to carbon 2.
 Three-
Carbon Stage
of Glycolysis
(Steps 4–10)

• Step 9: Dehydration: Formation of Phosphoenolpyruvate. The result is

another compound containing a high-energy phosphate group; the
phosphate group is attached to a carbon atom that is involved in a
carbon–carbon double bond
Three-Carbon Stage of Glycolysis (Steps 4–10)

• Step 10: Phosphorylation

of ADP: Formation of
Pyruvate.
Phosphoenolpyruvate
transfers its high-energy
phosphate group to an
ADP molecule to produce
ATP and pyruvate
8

9 10
Entry of Galactose and Fructose into Glycolysis
FATES OF PYRUVATE
 Oxidation to Acetyl CoA

• Under aerobic (oxygen-rich) conditions, pyruvate is oxidized to acetyl

CoA. Pyruvate formed in the cytosol through glycolysis crosses the two
mitochondrial membranes and enters the mitochondrial matrix, where
the oxidation takes place.
 Lactate Fermentation
• Fermentation is a biochemical process by which NADH is oxidized to NAD without the need for oxygen.
• Lactate fermentation is the enzymatic anaerobic reduction of pyruvate to lactate
• The sole purpose of this process is the conversion of NADH to NAD. The lactate so formed is
converted back to pyruvate when aerobic conditions are again established in a cell.
 This reaction, which involves both oxidation and
decarboxylation (because c02 is produced)

The overall reaction process involves four separate

Oxidation to steps and requires NAD, CoA—SH, FAD, and two other
coenzymes (lipoic acid and thiamine pyrophosphate,
Acetyl CoA the latter derived from the B vitamin thiamine)

Most acetyl CoA molecules produced from pyruvate

enter the citric acid cycle
 Lactate Fermentation
• When the reaction for conversion of pyruvate to lactate is added to
the net glycolysis reaction, an overall reaction for the conversion of
glucose to lactate is obtained:
 Ethanol Fermentation
• Ethanol fermentation is the enzymatic anaerobic conversion of pyruvate to ethanol and
carbon dioxide
• The first step in conversion of pyruvate to ethanol is a decarboxylation reaction to
produce acetaldehyde.
 Ethanol Fermentation
• The second step involves acetaldehyde reduction to produce ethanol.

• An overall reaction for the production of ethanol from glucose is

obtained by combining the reaction for the conversion of pyruvate
with the net reaction for glycolysis
Regeneration of NAD+ from NADH+
 ATP Production for the Complete Oxidation of
Glucose
• 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
PROTEIN METABOLISM
COLLEGE OF MEDICAL LABORATORY SCIENCE
OUR LADY OF FATIMA UNIVERSITY
 Protein Digestion and Absorption

Amino Acid Utilization

Transamination and Oxidative Deamination

The Urea Cycle

Objectives: Amino Acid Carbon Skeletons

Amino Acid Biosynthesis

Hemoglobin Catabolism

Interrelationship Among Metabolic Pathways

Protein Digestion and Absorption
Protein digestion (denaturation and hydrolysis) starts in the stomach:
• Denatured by HCl in gastric juice (pH of 1.5-2.0)
• Enzyme pepsin hydrolyzes about 10% peptide bonds

Large polypeptide chains pass from stomach into small intestine:

• pH in small intestine is 7.0 -8.0 and helps neutralize the acidified gastric content
• Trypsin, chymotrypsin and carboxypeptidase in pancreatic juice released into the small
intestine help hydrolyze proteins to smaller peptides
• Aminopeptidase secreted by intestinal mucosal membrane further hydrolyze the small
peptides to amino acids
• Amino acids (aa) liberated are transported into blood stream via active transport process
Protein Digestion and Absorption
• The passage of polypeptides and small proteins across the intestinal wall is
uncommon in adults.
• In infants the transport of polypeptides allows the passage of proteins such as
antibodies in colostral milk from a mother to a nursing infant to build up
immunologic protection in the infant.
• Enzymes (Trypsin, chymotrypsin carboxypeptidase , and aminopeptidase) are
produced in inactive forms called zymogens that are activated at their site of
action.
Protein Digestion and Absorption
Amino acids formed through digestion process enters the amino
acid pool in the body:
• Amino acid pool: the total supply of free amino acids
available for use in the human body
The amino acid pool is derived from 3 sources:
1. Dietary protein
2. Protein turnover: A repetitive process in which the body
proteins are degraded and resynthesized
3. Biosynthesis of amino acids in the liver
– only non-essential amino acids are synthesized
NITROGEN BALANCE
• The state that results when the amount of nitrogen taken into the human body as
protein equals the amount of nitrogen excreted from the body in waste materials.
• Two types of nitrogen imbalance can occur in human body:
Negative nitrogen imbalance: Protein degradation exceeds protein synthesis
Amount of N in urine exceeds nitrogen consumed
Results in tissue wasting
Positive nitrogen imbalance: Rate of protein synthesis (anabolism) is more than
protein degradation (catabolism)
Results in large amounts of tissue synthesis
During growth, pregnancy, etc.

Amino Acid Utilization

 AMINO ACIDS
Amino Acid Amino acids from the body's amino acid pool are used in four
different ways:

Utilization 1. Protein synthesis:

• About 75% of amino acids go into synthesis of proteins that is
needed continuous replacement of old tissues (protein
turnover) and to build new tissues (growth).
2. Synthesis of non-protein nitrogen-containing compounds:
• Synthesis of purines and pyrimidines for nucleic acid syntheis
• Synthesis of heme for hemoglobin, neutrotransmitters and
hormones
3. Synthesis of nonessential amino acids:
• Essential amino acids can’t be synthesized because of the lack
of appropriate carbon chain
4. Production of energy
• Amino acids are not stored in the body, so the excess is
degraded
• Each amino acid has a different mechanism of degradation
Amino Acid Utilization
DEGRADATION PATHWAYS
• The amino nitrogen atom is removed and
converted to ammonium ion, which ultimately is
excreted from the body as urea.
• The remaining carbon skeleton is then converted to
pyruvate, acetyl CoA, or a citric acid cycle
intermediate, depending on its makeup, with the
resulting energy production or energy storage.
 Degradation of an amino acid takes place in two
stages:
1. The removal of the -amino group and
2. The degradation of the remaining carbon
skeleton
TRANSAMINATION
Removal of amino group is a two step process
AND 1. Transamination- Biochemical process in
OXIDATIVE which the amino group of an alpha-amino
acid is transferred to an alpha-keto acid.
DEAMINATION 2. Oxidative deamination- an amino acid is
converted into the corresponding keto acid
by the removal of the amine functional
group as ammonia and the ammonia
eventually goes into the urea cycle.
 TRANSAMINATION AND OXIDATIVE
DEAMINATION
Transamination: Involves transfer of the amino group of an -amino acid to an alpha keto
acid as shown in the reaction below:
+ N H 3+
NH O O
3
+ - +
R CH COO- R' C COO R C CO O- R' C COO-
a - a m in o a c id a -k e t o a c id a -k e t o a c id H
a - a m in o a c id

• Transamination is an enzyme catalyzed reactions

• There are at least 50 transaminase enzymes associated with transamination
reactions
 TRANSAMINATION AND OXIDATIVE DEAMINATION

Initial effect of transamination: Collect the amino groups from a variety of amino
acids into just two amino acids—glutamate (most cells) and alanine (muscle cells)

• Net effect of transamination: Collection of the amino groups from a variety of

amino acids into a single compound—the amino acid glutamate
• To regenerate pyruvate and oxaloacetate for use in further transamination
reactions
 TRANSAMINATION AND OXIDATIVE
DEAMINATION
• Ammonium ion (NH4+) group is liberated from the glutamate amino acid
formed from transamination
• Oxidative deamination reaction is a biochemical reaction catalyzed by
glutamate dehydrogenase in which glutamate is converted into alpha-keto
glutarate with the release of an ammonium ion
• Occurs in liver and kidney

NAD+ NADH + H+

a-Glutamate + H2O a-Keto glutarate + NH4+

Glutamate
Dehydrogenase
 TRANSAMINATION AND OXIDATIVE
DEAMINATION
• The ammonium ion produced by oxidative deamination is a toxic substance, so it
is quickly converted carbomoyl phosphate and then to urea via the urea cycle in
mammals
• Two amino acids, serine and threonine, undergo direct deamination by
dehydration-hydration process rather than oxidative deamination
O
O O
O is o m e r iza tio n h y d r o ly s is
d e h y d ra tio n -
+ - +
H2N CH C O- O C C O
H2N CH C O
- H3N CH C O
CH 3 C H 3 p y ru va te
CH 2 CH 2

H 2O H 2O N H 4+
OH

s e r in e
UREA CYCLE
• The net effect of amino acid degradation is the
production of ammonium ion which is toxic and it is
converted to urea (relatively non-toxic compound)
in the liver via urea cycle.
• Urea cycle is a series of biochemical reactions in
which urea is produced from ammonium ions and
carbon dioxide.
• Urea is transported via the blood from liver to the
kidneys and eliminated from the body via urine.
• Urea:
❑ white solid
❑ melting point 133oC
❑ very soluble in water
❑ odorless and colorless and has a salty taste
 CARBAMOYL The fuel for the urea cycle
PHOSPHATE

Two ATP molecules are expended

in the formation of one
carbamoyl phosphate molecule
UREA CYCLE A high energy phosphate bond is
present in carbamoyl phosphate

It takes place in mitochondrial

matrix
 Stage 1: Carbomyl group transfer
• The carbamoyl group of carbamoyl phosphate is
transferred to ornithine to form citrulline

STEPS OF Stage 2: Citrulline-aspartate condensation

• Citrulline is transported into the cytosol, citrulline
THE UREA reacts with aspartate to produce argininosuccinate
utilizing ATP
CYCLE • In this reaction the second of two nitrogen atoms
of urea is introduced into the cycle (One nitrogen
comes from carbamoyl phosphate and the other
from aspartate -- original source of both is
glutamate)
 Stage 3: Argininosuccinate cleavage:
• Argininosuccinate is cleaved to arginine and
fumarate by the enzyme argininosuccinate lyase

STEPS OF Stage 4: Hydrolysis of urea from arginine:

THE UREA • Hydrolysis of arginine produces urea and
regenerates ornithine - one of the cycle’s starting
CYCLE materials
• The oxygen atom present in the urea comes from
water
• Orthinine is transported back to mitochondria to
be used in the urea cycle
 UREA CYCLE NET REACTION
• Total of four ATP molecules is expended
in the production of one urea cycle
molecule
UREA CYCLE ❑Two molecules are consumed in the
production of carbamoyl phosphate
and the equivalent of two ATP
molecule is consumed in step 2 of
the urea cycle to give AMP and two Pi
Linkage Between the
Urea and Citric Acid
Cycles
• Fumarate
produced is used in
citric acid cycle
• Aspartate
produced through
transamination is
used in the urea
cycle at step 2
Transamination and oxidative deamination produces an alpha-keto acid that contains
the carbon skeleton from the amino acid

Each of 20 amino acids carbon skeletons undergo a different degradation process

Degraded products are pyruvate, acetyl CoA, acetoacetyl CoA, alpha-ketoglutarate,

succinyl CoA, fumarate, and oxaloacetate
• Last four are intermediates in the citric acid cycle

AMINO ACID CARBON SKELETONS

The amino acids converted to
citric acid cycle intermediates
can serve as glucose
precursors (glucogenic amino
acids).
• Glucogenic amino acid: An amino acid that has a
carbon-containing degradation product that can
be used to produce glucose via gluconeogenesis.

The amino acids converted to

acetyl CoA or acetoacetyl CoA • Ketogenic amino acid: An amino acid that has a
can serve as fatty acids and/or carbon-containing degradation product that can
ketone body precursors be used to produce ketone bodies
(ketogeneic amino acids)

AMINO ACID CARBON SKELETONS

Fates of
Carbon
Skeletons of
Amino Acids
 Non essential Essential amino
amino acids are acids are
synthesized in synthesized in
1-3 steps 7-10 steps
AMINO ACID
BIOSYNTHESIS
Diet with lack
Excess amino
of high quality
acids are
proteins results
converted to
in breakage of
fat and stored
body proteins
Summary of the Starting Materials for the Biosynthesis
of the 11 Nonessential Amino Acids
 HEMOGLOBIN
CATABOLISM
• Red blood cells (RBCs) are highly
specialized cells whose primary
function is to deliver oxygen to cells
and remove carbon dioxide from body
tissues
• Mature red blood cells have no
nucleus or DNA -- filled with red
pigment hemoglobin
• Red blood cells are formed in the bone
marrow
~ 200 billion new red blood cells are
formed daily
• The life span of a red blood cell is
about 4 months
 HEMOGLOBIN
CATABOLISM
• Hemoglobin is a
conjugated protein with two
parts:
❑ Protein portion is
globin
❑ Prosthetic group is
heme
• Iron atom interacts with
oxygen forming a reversible
complex (oxygen can come
on and off) with it
 HEMOGLOBIN
CATABOLISM
• Old RBCs are broken down in the spleen
(primary site) and liver (secondary site):
• Degradation of hemoglobin
❑ Globin protein part is converted to
amino acids and are put in amino acid
pool
❑ Fe atom becomes part of ferritin -- an
iron storage protein -- saves the iron
for use in biosynthesis of new
hemoglobin molecules
❑ The heme (tetrapyrrole) is degraded to
bile pigments and eliminated in feces
or urine.
 HEMOGLOBIN CATABOLISM
BILE PIGMENTS
• Bile pigments: The tetrapyrrole degradation products secreted via the bile.
• There are four bile pigments:
1. Biliverdin - green in color
2. Bilirubin - reddish orange in color.
3. Stercobilin – brownish in color (gives feces their characteristic brown color).
4. Urobilin - yellow in color and present in urine (gives characteristic yellow color to
urine).
• Daily normal excretion of bile pigments: 1–2 mg in urine and 250–350 mg in feces.
• Jaundice: Results from liver, spleen and gallbladder malfunction.
❑ Results in higher than normal bilirubin levels in the blood and gives the skin and
white of the eye yellow tint.
INTERRELATIONSHIP AMONG METABOLIC PATHWAYS
• The metabolic pathways of carbohydrates, lipids, and proteins are
integrally linked to one another.
− A change in one pathway can affect many other pathways.
Examples:
− Feasting (over eating): Causes the body to store a limited
amount as glycogen and the rest as fat.
− Fasting (no food ingestion): The body uses its stored glycogen
and fat for energy.
− Starvation (not eating for a prolonged period):
❑ Glycogen stores are depleted,
❑ Body protein is broken down to amino acids to synthesize glucose.
❑ Fats are converted to ketone bodies.
 Chapter 25

Lipid Metabolism
 Chapter 25
Table of Contents
25.1 Digestion and Absorption of Lipids
25.2 Triacylglycerol Storage and Mobilization
25.3 Glycerol Metabolism
25.4 Oxidation of Fatty Acids
25.5 ATP Production from Fatty Acid Oxidation
25.6 Ketone Bodies
25.7 Biosynthesis of Fatty Acids: Lipogenesis
25.8 Relationship Between Lipogenesis and Citric Acid Cycle
Intermediates
25.9 Biosynthesis of Cholesterol
25.10 Relationships Between Lipid and Carbohydrate Metabolism

Copyright © Cengage Learning. All rights reserved 2

 Section 25.1
Digestion and Absorption of Lipids

• Dietary Lipids: 98% triacylglycerols (TAGs):

– Fats and oils
• Salivary enzymes (water soluble) in the mouth have no
effect on lipids (TAGs) which are water insoluble
• In Stomach: Most, not all, of TAGs change physically to
small globules or droplets -- called chyme which floats
above other material:
– It is a physical not chemical process -- enters into
small intestine

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Copyright © Cengage Learning. All rights reserved 3

 Section 25.1
Digestion and Absorption of Lipids

• Lipid digestion starts in the stomach:

– Gastric lipase hydrolyzes ester bonds -- 2 fatty acids
and one monoacylglycerol --About 10% of TAGS are
hydrolyzed
• High fat foods stay in stomach for longer time -- high fat meal
gives you a feeling of being full for longer time

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Copyright © Cengage Learning. All rights reserved 4

 Section 25.1
Digestion and Absorption of Lipids

• Chyme enters into small intestine and is emulsified

(stabilization of colloidal suspension) with bile salts
• Pancreatic lipase hydrolyzes ester bonds of fatty acids
and glycerol
– Normally 2 out of 3 fatty acids are hydrolyzed
• Fatty acids, monoacyglycerols and bile salts make small
droplets: called micelles -- hydrophobic chain in the
interior
• Micelles consist of monoacyglycerols and free fatty
acids:
– Small enough to absorb through intestinal cells
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Copyright © Cengage Learning. All rights reserved 5

 Section 25.1
Digestion and Absorption of Lipids

• In the intestinal cells monoacylglycerols and free fatty acids are

repackaged to from TAGs
• These new TAGs combine with membrane lipids (phospholipids and
cholesterol) and lipoproteins to form chylomicron
• Chylomicrons transport TAGs from intestinal cells to the
bloodstream
– This is accomplished though the lymphatic system
• In the bloodstream TAGs are completely hydrolyzed by lipase
enzymes
• Fatty acids and glycerol are absorbed by the cell and are either
broken down to the acetyl Co-A for energy or repacked to store as
lipids

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Copyright © Cengage Learning. All rights reserved 6

 Section 25.2
Triacylglycerol Storage and Mobilization

• Most cells have limited capability of TAGs storage

• TAGs stored in specialized cells called adipocytes found
in adipose tissue:
– Largest cells in the body -- cytoplasm converted to TAG’s
droplet
– Located primarily beneath the skin especially in abdominal
region and vital organs
– Adipose tissue also serve as a protection against the heat loss
and mechanical shock

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Copyright © Cengage Learning. All rights reserved 7

 Section 25.2
Triacylglycerol Storage and Mobilization

• Several hormones trigger the hydrolysis of TAGs via

activation of cAMP (activate hormone sensitive lipase;
HSL) and release of glycerol and fatty acids into the
bloodstream -- called triacylglycerol mobilization
• ~10% of TAGs replaced everyday
• Triacylglycerol energy reserves (fat reserves) are the
human body’s major source of stored energy:
– Energy reserves associated with protein, glycogen,
and glucose are small to very small when compared
to fat reserves

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Copyright © Cengage Learning. All rights reserved 8

 Section 25.3
Glycerol Metabolism

• Taken to liver or kidney by blood -- converted to

dihydroxyacetone phosphate in two steps:
– Phosphorylation of primary hydroxyl group of the
glycerol
– Secondary alcohol group of glycerol is oxidized to
ketone

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Copyright © Cengage Learning. All rights reserved 9

 Section 25.4
Oxidation of Fatty Acids

• There are three parts to the process by which fatty acids

are broken down to obtain energy.
• Activated by binding to Coenzyme-A - product called
acyl Co-A.
• Transported to mitochondrial matrix
• Repeatedly (fatty acid spiral) oxidized to produce acetyl
Co-A, FADH2 and NADH
• note acyl has longer R group but acetyl has CH3
attached to C=O

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Copyright © Cengage Learning. All rights reserved 10

 Section 25.4
Oxidation of Fatty Acids

Fatty Acid Activation

• Takes place in outer mitochondrial membrane
• FA reacts with coenzyme A in the presence of ATP to
produce high energy acyl CoA
• ATP is converted to AMP

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Copyright © Cengage Learning. All rights reserved 11

 Section 25.4
Oxidation of Fatty Acids

Fatty Acid Transport

• A shuttle mechanism is involved in the transport of acyl
CoA from mitochondrial membrane to mitochondrial
matrix

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Copyright © Cengage Learning. All rights reserved 12

 Section 25.4
Oxidation of Fatty Acids

Reactions of the Beta-Oxidation Pathway

• Four reactions repeatedly cleaves two-carbon units from
the carboxyl end of saturated fatty acids
– Also called b-oxidation spiral because the second or
beta carbon from carboxyl end of the chain oxidized
• This process removes two carbon units and converts to
acetyl CoA with FADH2 and NADH being produced

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Copyright © Cengage Learning. All rights reserved 13

 Section 25.4
Oxidation of Fatty Acids

Four Steps of the Beta-Oxidation Pathway

• Step 1: Oxidation (dehydrogenation):
– Hydrogen atoms are removed from the a and b
carbons, creating a double bond between these two
carbon atoms.
– FAD is the oxidizing agent, and a FADH2 molecule is
a product.

• Step 2: Hydration:
– A molecule of water is added across the trans double
bond, producing a secondary alcohol at the b-carbon
position
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Copyright © Cengage Learning. All rights reserved 14

 Section 25.4
Oxidation of Fatty Acids

Four Steps of the Beta-Oxidation Pathway

• Step 3: Oxidation (dehydrogenation):
– The b-hydroxy group is oxidized to a ketone
functional group with NAD+ serving as the oxidizing
agent.

• Step 4: Chain Cleavage:

– The fatty acid chain is broken between the a and b
carbons by reaction with a coenzyme A molecule.
– The result is an acetyl CoA molecule and a new acyl
CoA molecule that is shorter by two carbon atoms
than its predecessor.
Return to TOC

Copyright © Cengage Learning. All rights reserved 15

 Section 25.4
Oxidation of Fatty Acids

Unsaturated Fatty Acids

• Oxidation of unsaturated FAs require two additional
steps compared to saturates FAs
• Epimerase: changes D-configuration to an L
configuration
• Cis-trans isomerase: trans-(2,3) double bond is formed
from cis-(3,4) double bond

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Copyright © Cengage Learning. All rights reserved 16

 Section 25.5
ATP Production From Fatty Acid Oxidation

Fatty Acid vs. Glucose Oxidation: A Comparison

• Spiral fatty acid oxidation (previous slide) produce net 120 ATP
molecules by oxidation of 18 carbon atom fatty acid (stearic acid)
• Note that 2 ATP molecules are needed for activation of fatty acids so
net ATP production is 120 molecules
• 1 Glucose molecule (6 carbon atoms) produces 30 ATP molecules
• Three molecules of glucose (18 Carbon atoms) produce 90 ATP
• 1 Stearic acid molecule (18 carbon atoms) produces 122 molecules
of ATP 10 ATP
9 Acetyl CoA x = 90 ATP
1 Acetyl CoA
1.5 ATP
8 FADH2 x = 12 ATP
1 FADH2
2.5 ATP
8 NADH x = 20ATP
1 NADH
Total = 122 ATP Return to TOC

Copyright © Cengage Learning. All rights reserved 17

 Section 25.5
ATP Production From Fatty Acid Oxidation

Fatty Acid vs. Glucose Oxidation: A Comparison

• Stoichiometric Comparison:
– 1.00 g Stearic acid produces = 0.423 mole ATP
– 1.00 g glucose produces 0.167 mole ATP
• Stearic acid produces 2.5 time more energy than glucose

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Copyright © Cengage Learning. All rights reserved 18

 Section 25.6
Ketone Bodies

• Acetyl CoA formed from fatty acid spiral further

processed by Citric Acid Cycle (Krebs Cycle) – Therefore
an adequate balance in carbohydrate and lipid
metabolism required
• Lipid-Carbohydrate Metabolism disturbed by:
– Dietary intakes high in fat and low in carbohydrates
– Diabetic conditions -- glucose not used properly
– Prolonged fasting conditions

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Copyright © Cengage Learning. All rights reserved 19

 Section 25.6
Ketone Bodies

• Under low supply of oxaloacetate the acetyl CoA will be

in excess (increased concentration)
• As a consequence the excess acetyl CoA is converted to
ketone bodies

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Copyright © Cengage Learning. All rights reserved 20

 Section 25.6
Ketone Bodies

Ketogenesis
• Ketogenesis involves the production of ketone bodies
from acetyl CoA
• Synthesis of ketone bodies from acetyl CoA primarily in
liver mitochondria -- diffused into blood stream and
transported to peripheral tissues

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Copyright © Cengage Learning. All rights reserved 21

 Section 25.6
Ketone Bodies

Ketogenesis
• Step 1: First Condensation of two acetyl CoA molecules
to produce acetoacetyl CoA, a reversal of the last step of
the Beta-oxidation pathway
• Step 2: Second Condensation: Acetoacetyl CoA then
reacts with a third acetyl CoA and water to produce 3-
hydroxy-3-methylglutaryl CoA (HMG-CoA) and CoA-SH.
• Step 3: Chain cleavage: HMG-CoA is cleaved to acetyl
CoA and acetoacetate.
• Step 4: Reduction: Acetoacetate is reduced to Beta-
hydroxybutyrate.

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Copyright © Cengage Learning. All rights reserved 22

 Section 25.6
Ketone Bodies

Summary of Ketogenesis

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Copyright © Cengage Learning. All rights reserved 23

 Section 25.7
Biosynthesis of Fatty Acids: Lipogenesis

Lipogenesis vs. Fatty Acid Degradation

Lipogenesis Degradation of a fatty acids

Takes place in cell cytosol Takes place in
mitochondrial matrix
A multi-enzyme complex Enzymes are not complexed
called fatty acid synthase and the steps are
catalyzes reactions independent
Intermediates bonded to The carrier for fatty acid
acyl carrier protein (ACP) spiral is CoA
Depends upon reducing Dependent upon FAD and
agent NADPH NAD+
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Copyright © Cengage Learning. All rights reserved 24

 Section 25.7
Biosynthesis of Fatty Acids: Lipogenesis

The Citrate–Malate Shuttle System

• Acetyl CoA is the
starting material for
lipogenesis.
• Acetyl CoA needed for
lipogenesis is
generated in
mitochondria therefore
it must first be
transported to the
cytosol.
• Citrate-malate transport
system helps transport
acetyl CoA to cytosol
indirectly.
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Copyright © Cengage Learning. All rights reserved 25

 Section 25.7
Biosynthesis of Fatty Acids: Lipogenesis

ACP Complex Formation

• ACP Complex Formation:
– All intermediates in fatty acid synthesis are linked to
carrier proteins (ACP-SH)
– ACP-SH can be regarded as a “giant CoA-SH
molecule”

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Copyright © Cengage Learning. All rights reserved 26

 Section 25.7
Biosynthesis of Fatty Acids: Lipogenesis

Chain Elongation
• Four reactions constitute first step of chain elongation
process
– Condensation: Acetyl-ACP and malonyl-ACP
condense together to form acetoacetyl-ACP
– Hydrogenation: The keto group of the acetoacetyl
complex is reduced to alcohol by NADPH
– Dehydration: Water is removed from alcohol to form
an alkene
– Hydrogenation: Hydrogen is added to alkene 3 to
form saturated butyryl ACP from NADPH

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Copyright © Cengage Learning. All rights reserved 27

 Section 25.7
Biosynthesis of Fatty Acids: Lipogenesis

Unsaturated Fatty Acid Biosynthesis

• To produce a double bond oxygen is needed and water
is removed
• In humans and animals, enzymes can only introduce
double bond between C-4 and C-5 and between C-9 and
C-10
• Consequence: Important essential unsaturated fatty
acids linoleic (18 carbons with C-9 and C-12 double
bond and linolenic acid (18 carbon with C-9, C-12 and C-
15 double bonds can’t be synthesized - should come
from diet - plants have enzymes to synthesize them

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Copyright © Cengage Learning. All rights reserved 28

 Section 25.8
Relationships Between Lipogenesis and Citric Acid Cycle Intermediates

• The last four intermediates of the citric acid cycle bear

the following relationship to each other.
• Saturated C4 diacid → Unsaturated C4 diacid → hydroxy
C4 diacid → keto C4 diacid.
• The intermediate C4 carbon chains of lipogenesis bear
the following relationship to each other.
• Keto C4 monoacid → hydroxy C4 monoacid →
unsaturated C4 monoacid → saturated C4 monoacid.

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Copyright © Cengage Learning. All rights reserved 29

 Section 25.8
Relationships Between Lipogenesis and Citric Acid Cycle Intermediates

• Two important contrasts between citric acid cycle

intermediates and Lipogenesis intermediates:
– The citric acid intermediates involve C4 diacids and
the lipogenesis intermediates involve C4 monoacids
– The order in which the various acid derivative types
are encountered in lipogenesis is the reverse of the
order in which they are encountered in the citric acid
cycle.

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Copyright © Cengage Learning. All rights reserved 30

 Section 25.9
Biosynthesis of Cholesterol

Cholesterol
• Secondary component of cell membrane
• Precursor for bile salts, sex hormones and adrenal
hormone
• Body synthesizes 1.5 - 2.0 g of cholesterol everyday
from acetyl CoA units
– Average daily dietary intake is ~ 0.3 g
• Synthesis of cholesterol occur in liver
• Synthesis requires at least 15 acetyl CoAs and involves
~27 separate enzymetic steps

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Copyright © Cengage Learning. All rights reserved 31

 Section 25.9
Biosynthesis of Cholesterol
An Overview of the Biosynthetic Pathway for Cholesterol
Synthesis

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Copyright © Cengage Learning. All rights reserved 32

 Section 25.9
Biosynthesis of Cholesterol

Biosynthetic Relationships Among Steroid Hormones

• Once cholesterol is synthesized, it is converted to
five major classes of steroid hormones: progestins,
androgens, estrogens and vitamin D

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Copyright © Cengage Learning. All rights reserved 33

 Section 25.10
Relationships Between Lipid and Carbohydrate Metabolism

• Acetyl Co-A is the primary link between these two

metabolic pathways
– Acetyl Co-A is the starting material for the
biosynthesis of fatty acids, cholesterol and ketone
bodies
– Acetyl CoA is the product for glucose, glycerol and
fatty acids

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 Section 25.10
Relationships Between Lipid and Carbohydrate Metabolism

Four Possible Fates of Acetyl CoA

• Oxidation in the citric acid cycle: both lipids and
carbohydrates supply acetyl CoA
• Ketone body formation: Very important when imbalance
between carbohydrate and lipid metabolism
• Fatty acid biosynthesis: the buildup of excess acetyl CoA
when dietary intake exceeds energy needs energy
needs leads to accelerated fatty acid biosynthesis
• Cholesterol biosynthesis: It occurs when the body is in
an acetyl CoA- rich state

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