An Overview of Biochemical Energy Production

• The energy needed to run the human body is obtained from ingested food
through a multistep process that involves several different catabolic
pathways.
• There are four(4) general stages in the biochemical energy production
process, and numerous reactions are associated with each stage.
• Stage 1. The 1st stage, digestion, begins in the mouth (saliva contains
starch-digesting enzymes), continues in the stomach (gastric juices), and is
completed in the small intestine(the majority of digestive enzymes and
bile salts).
• The end products of digestion – glucose and other monosaccharides from
carbohydrates, amino acids from proteins, and fatty acids and glycerol
from fats and oils– are small enough to pass across intestinal membranes
and into the blood, with the aid of membrane transport systems.
• Once in the blood, they are then distributed to the cells in various parts of
the body.
 Stage 2. The 2nd stage, acetyl group formation, involves
numerous reactions, some of which occur in the cytosol of cells
and some in cellular mitochondria.
The small molecules from digestion are further oxidized during this
stage. Primary products include two-carbon acetyl units( which
become attached to coenzyme A to give acetyl CoA) and the
reduced coenzyme NADH.
Stage 3. The 3rd stage, the citric acid cycle, occurs inside
mitochondria. Here acetyl groups are oxidized to produce CO2 and
energy.
Some of the energy released by these reactions is lost as heat, and
some is carried by the reduced coenzymes NADH and FADH2 to the
4th stage.
The CO2 that is exhaled as part of the breathing process comes
primarily from this stage.
Stage 4. The 4th stage, the electron transport chain and oxidative phosphorylation,
also occurs inside mitochondria. NADH and FADH2 supply the “fuel”( hydrogen ions
and electrons) needed for the production of ATP molecules, the primary energy
carriers in metabolic pathways.
Molecular O2, inhaled via breathing, is converted to H2O in this stage.
The reactions in stages 3 and 4 are the same for all types of foods ( carbohydrates,
fats, proteins).
These reactions constitute the common metabolic pathway.
What is a common metabolic pathway?
The reactions of stages 1 and 2 of biochemical energy production
differ for different types of foodstuffs.
B Vitamins and the Common Metabolic Pathway
B vitamins function as coenzymes in metabolic pathways and are involved in the
citric acid cycle and the electron transport chain.
The four(4) vitamins that have involvement in the metabolic reactions are:
1. Niacin—as NAD+ and NADH
2. Riboflavin--- as FAD, FADH2 and FMN
3. Thiamin---as TPP
4. Pantothenic acid ---- as CoA
• Vitamins and minerals play a different kind of role in energy
metabolism; they are required as functional parts of enzymes
involved in energy release and storage. The water-soluble B
vitamins are involved as coenzymes in the breakdown of
nutrients and in the building of macromolecules, such as
protein, RNA, and DNA.
• The reactions in stages 3 and 4 are the same for all types of foods
(carbohydrates, fats, proteins).
• These reactions constitute the common metabolic pathway.
• The common metabolic pathway is the sum total of the
biochemical reactions of the citric acid cycle, the electron
transport chain, and oxidative phosphorylation.
• The reactions of stages 1 and 2 of biochemical energy production
differ for different types of foodstuffs. (Metabolism of
carbohydrates, fats (lipids), and proteins, respectively.
• Simplified Summary of the Four Stages of Biochemical Energy
Production –summarizes the four general stages in the process of
production of biochemical energy from ingested food.
• This diagram is a very simplified version of the “energy generation”
process that occurs in the human body,
 Biochemical Energy Production
• Metabolism is the sum total of all the biochemical reactions
that take place in a living organism.
• Metabolic reactions fall into one of two subtypes:
• catabolism and anabolism
• Catabolism is all metabolic reactions in which large
biochemical molecules are broken down to smaller ones.
• Catabolic reactions usually release energy.
• The reactions involved in the oxidation of glucose are catabolic.

• Anabolism is all metabolic reactions in which small

biochemical molecules are joined together to form larger ones.
• Anabolic reactions usually require energy in order to proceed.
• The synthesis of proteins from amino acids is an anabolic
process.
• The metabolic reactions that occur in a cell are
usually organized into sequences called
metabolic pathways.
• A metabolic pathway is a series of consecutive
biochemical reactions used to convert a starting
material into an end product.
• Such pathways may be linear, in which a series of
reactions generates a final product, or cyclic, in
which a series of reactions regenerates the first
reactant.
• Cells are of two types: prokaryotic and
eukaryotic
• Prokaryotic cells have no nucleus and are
found only in bacteria.
• The DNA that governs the reproduction of
prokaryotic cells is usually a single circular
molecule found near the center of the cell in a
region called the nucleoid.
• A eukaryotic cell is a cell in which the DNA is
found in a membrane-enclosed nucleus.
• Cytoplasm is the water-based material of a eukaryotic
cell that lies between the nucleus and the outer
membrane of the cell.
• Within the cytoplasm are kinds of small structures
called organelles.
• An organelle is a minute structure within the
cytoplasm of a cell that carries out a specific cellular
function.
• The organelles are surrounded by the cytosol.
• The cytosol is the water-based fluid part of the
cytoplasm of a cell.
• Three important types of organelles:
• ribosomes, lysosomes and mitochondria
• Ribosomes are the sites where protein synthesis
occurs.
• A lysosome is an organelle that contains hydrolytic
enzymes needed for cellular rebuilding, repair, and
degradation.
• Some lysosome enzymes hydrolyze proteins to
amino acids; others hydrolyze polysaccharides to
monosaccharides.
• Bacteria and viruses “trapped” by the body’s
immune system are degraded and destroyed by
enzymes from lysosomes.
• A mitochondrion is an organelle that is responsible
for the generation of most of the energy for a cell.

• Mitochondria are sausage-shaped organelles

containing both an outer membrane and a
multifolded inner membrane.

• The outer membrane, which is about 50% lipid and

50% protein, is freely permeable to small molecules.

• The inner membrane, which is about 20% lipid and

80% protein, is highly impermeable to most
substances.
The internal structural components of a Mitochondrion
• The nonpermeable nature of the inner membrane divides a
mitochondrion into two separate compartments- an interior
region called the matrix and the region between the inner
and outer membranes, called the inter-membrane space.

• The folds of the inner membrane that protrude into the matrix
are called cristae.

• The interior structure of the mitochondrion, are the small

spherical knobs attached to the cristae called ATP synthase
complexes.

• These relatively small knobs, which are located on the matrix

side of the inner membrane are responsible for ATP synthesis.
 Important Nucleotide-Containing Compounds
in Metabolic Pathways

• The metabolic processes by which our food is

converted to energy, are several compounds
that function as key intermediates in metabolic
pathways.
• These compounds all have nucleotides as part of
their structures.
• The following are the compounds: ATP, ADP,
AMP, FAD, FADH, NAD+, NADH and CoA-SH
• Nucleotide – is a compound consisting of a nucleoside linked to a
phosphate group.
• Nucleotides form the basic structural unit of nucleic acids such as DNA.
Metabolic pathway
A metabolic pathway is a series of biochemical reactions by which an
organism converts a given reactant to a specific end product. There are
specific metabolic pathways—which are different for carbohydrates,
triglycerides, and proteins—that break down the products of stage I of
catabolism (monosaccharides, fatty acids, and amino acids) to produce a
common end product, acetyl-coenzyme A (acetyl-CoA) in stage II of
catabolism.
Anabolism and catabolism are the two broad classes of biochemical
reactions that make up metabolism.
Anabolism is the synthesis of complex molecules from simpler ones. These
chemical reactions require energy.
Catabolism is the breakdown of complex molecules into simpler ones.
• The citric acid cycle is the final common pathway for the
oxidation of fuel molecules—amino acids, fatty acids, and
carbohydrates.
• The citric acid cycle is the 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.
• This cycle, stage 3 of biochemical energy production, gets its
name from the first intermediate product in the cycle, citric acid.
• It is also known as the Krebs cycle, after its discoverer Hans Adolf
Krebs, and as the tricarboxylic acid cycle, in reference to the three
carboxylate groups present in the citric acid.
• The chemical reactions of the citric acid cycle take place in the
mitochondrial matrix where the needed enzymes are found,
except the succinate dehydrogenase reaction that involves FAD.
 Adenosine Phosphates (ATP,ADP, and AMP)
• Several adenosine phosphates exist. Of importance in
metabolism are: adenosine monophosphate (AMP), adenosine
diphosphate (ADP), and adenosine triphosphate (ATP).
• AMP is one of the nucleotides present in RNA molecules.
• ADP and ATP differ structurally from AMP only in the number of
phosphate groups present.
• The three(3) adenosine phosphates have bonds that the
phosphate groups participate in.
• The phosphate –ribose bond is a phosphoester bond and the
phosphate –phosphate bonds are phosphoanhydride bonds.
• The word anhydride present in the term phosphoanhydride refers
to the production of (loss of) a molecule of water when two
phosphate groups bond to each other.
 Nicotinamide Adenine Dinucleotide (NAD+, NADH)
• Several parallels exist between the characteristics of nicotinamide
adenine dinucleotide and those of FAD/FADH2.
• Both have coenzyme functions in metabolic redox pathways, both
have a B vitamin as a structural component, both can be
represented structurally by using a three-subunit and six-subunit
formulation, and both have an oxidized and a reduced form.
• The notation for the oxidized form of nicotinamide adenine
dinucleotide is NAD + and that for the reduced form is NADH.
• The B vitamin present in NAD+/NADH is nicotinamide.
• A phosphoanhydride bond is the chemical bond formed when two
phosphate groups react with each other and a water molecule is
produced.
• A phosphoryl group, which has the formula PO32-, is the
functional group derived from a phosphate ion when the latter
becomes part of another molecule.
• ATP contains three phosphoryl groups, ADP two phosphoryl
groups, and AMP one phosphoryl group.
• ATP and ADP molecules readily undergo hydrolysis reactions in
which phosphate groups (Pi, inorganic phosphate) are released.
• The enzyme that catalyzes this reaction is an integral part of the
inner mitochondrial membrane.
• The individual steps of the cycle are now considered in detail.
• Oxidation, which produces NADH or FADH2, is encountered in
four of the eight steps, and decarboxylation, wherein a carbon
chain is shortened by the removal of a carbon atom as a CO2
molecule, is encountered in two of the eight steps.
• An Overview of the Citric Acid Cycle:
• The citric acid cycle is the central metabolic hub of
the cell.
• It is the gateway to the aerobic metabolism of any
molecule that can be transformed into an acetyl
group or dicarboxylic acid.
• The cycle is also an important source of precursors,
not only for the storage forms of fuels, but also for
the building blocks of many other molecules such as
amino acids, nucleotide bases, cholesterol, and
porphyrin (the organic component of heme).
• What is the function of the citric acid cycle in
transforming fuel molecules into ATP?
• Recall that fuel molecules are carbon compounds
that are capable of being oxidized—of losing
electrons.
• The citric acid cycle includes a series of oxidation-
reduction reactions that result in the oxidation of an
acetyl group to two molecules of carbon dioxide.
• The overall pattern of the citric acid cycle is shown in
the Figure where four- carbon compound
(oxaloacetate) condenses with a two-carbon acetyl
unit to yield a six-carbon tricarboxylic acid (citrate).
• An isomer of citrate is then oxidatively
decarboxylated.
• The resulting five-carbon compound (α-
ketoglutarate) also is oxidatively decarboxylated to
yield a four-carbon compound (succinate).
• Oxaloacetate is then regenerated from succinate.
• Two carbon atoms enter the cycle as an acetyl unit
and two carbon atoms leave the cycle in the form of
two molecules of carbon dioxide.
• Three hydride ions (hence, six electrons) are
transferred to three molecules of nicotinamide
adenine dinucleotide (NAD+), whereas one pair of
hydrogen atoms (hence, two electrons) is transferred
to one molecule of flavin adenine dinucleotide (FAD)
• The function of the citric acid cycle is the
harvesting of high-energy electrons from
carbon fuels.

• Note that the citric acid cycle itself neither

generates a large amount of ATP nor includes
oxygen as a reactant Instead, the citric acid
cycle removes electrons from acetyl CoA and
uses these electrons to form NADH and FADH2.
• In oxidative phosphorylation , electrons released in
the reoxidation of NADH and FADH2 flow through a
series of membrane proteins (referred to as
the electron-transport chain) to generate a proton
gradient across the membrane.
• These protons then flow through ATP synthase to
generate ATP from ADP and inorganic phosphate.
• Oxygen is required for the citric acid cycle indirectly
inasmuch as it is the electron acceptor at the end of
the electron-transport chain, necessary to
regenerate NAD+ and FAD.
• ATP is not the only nucleotide triphosphate present in cells,
although it is the most prevalent.
• The other nitrogen-containing bases associated with
nucleotides are also present in triphosphate form.
• Uridine triphosphate (UTP) is involved in carbohydrate
metabolism, guanosine triphosphate (GTP) participates in
protein and carbohydrate metabolism, and cytidine
triphosphate (CTP) is involved in lipid metabolism.
• Adenosine Phosphates and Muscle Relaxation/Contraction-
provides an additional example of the use of energy
obtained from ATP hydrolysis in the operation of the human
body.
• This example involves muscle contraction and relaxation.
 Flavin Adenine Dinucleotide (FAD, FADH2)

• Flavin adenine dinucleotide (FAD) is a coenzyme required in

numerous metabolic redox reactions.
• Structurally, FAD can be visualized as containing either three
subunits or six subunits.
• The flavin and ribitol subunits in this structure together constitute
the B vitamin riboflavin.
• The coenzyme FAD is thus one of the biochemically active forms of
riboflavin; the activating factor is the ADP subunit.
• The block diagram shows the basis for the name flavin adenine
dinucleotide,
• Ribitol is a reduced form of ribose; a –CH2OH group is present in
place of the –CHO group.
• In examining what happens to coenzymes such as FAD
when they participate in redox reactions, the definitions
for oxidation and reduction used are those that relate to
hydrogen atom change.
• These definitions are:
• 1. Oxidation involves hydrogen atom loss.
• 2. Reduction involves hydrogen atom gain.
• Also, in order to better keep track of changes that occur
within a coenzyme as a result of oxidation or reduction,
it is convenient to consider hydrogen atoms
participating in redox reactions as being composed of a
proton (H+) and an electron (e-).
• Note: Two(2) hydrogens participate as reactants in a
redox process as: 2H+ + 2e- rather than as 2H.
• Flavin adenine dinucleotide has two forms – an oxidized form
and a reduced form.
• The notation FAD denotes the oxidized form.
• The reduced form, denoted by the notation FADH contains two
more H atoms than the oxidized form, which is consistent with
the process of reduction involving hydrogen atom gain.
• FAD + 2H+ + 2e- FADH2
• oxidized form reduced form
• The active portion of flavin adenine dinucleotide in redox
reactions is the flavin subunit of the molecule.
• It is this portion of the molecule that undergoes change (gains
hydrogen atoms) when the oxidized form (FAD) is converted to
the reduced form (FADH2).
 Non-ETC Oxygen- Consuming Reactions
• The electron transport chain/oxidative phosphorylation phase of
metabolism consumes more than 90% of the oxygen taken into
the human body via respiration.
• What happens to the remainder of the inspired O2?
• As a normal part of metabolic chemistry, significant amounts of
this remaining O2 are converted into several highly Reactive
Oxygen Species (ROS).
• Among these ROS are : hydrogen peroxide(H2O2), superoxide
ion(O2-), and hydroxyl radical(OH ).
• The latter two of these substances are free radicals, substances
that contain an unpaired electron.
• Reactive oxygen species (ROS) have beneficial functions within
the body, but they can also cause problems if they are not
eliminated when they are longer needed.
• White blood cells have a significant concentration of
superoxide free radicals.
• Here, these free radicals aid in the destruction of
invading bacteria and viruses.
• NADPH is a phosphorylated version of the coenzyme
NADH.
• Superoxide ion that is not needed is eliminated from
cells in a two-step process governed by the enzymes
superoxide dismutase and catalase, two of the most
rapidly working enzymes known.
• In the 1st step, superoxide ion is converted to hydrogen
peroxide, which is then, in the 2ndstep, converted to
H2O.
Immediate destruction of the hydrogen peroxide is critical, because
if it persists , then unwanted production of hydroxyl radical would
occur via hydrogen peroxide’s reaction with superoxide ion.

Hydroxyl radicals quickly react with other substances by taking an

electron from them. Such action usually causes bond breaking.

Lipids in cell membranes are particularly vulnerable to such attack

by hydroxyl radicals.

It is estimated that 5% of the ROS escape destruction through

normal channels(superoxide dismutase and catalase).

Operating within a cell is a backup system- a network of

antioxidants- to deal with this problem.
• Participating in this antioxidant network are glutathione and
beta- carotene and vitamin E, as well as numerous compounds,
known as phytochemicals, obtained from plants through dietary
intake.
• A phytochemical is a nonnutrient compound found in plant-
derived foods that has a positive effect on human health.
• Note: while most antioxidants are found in the foods you eat,
glutathione is produced by your body.
• It is primarily made up of three amino acids:
• glutamine, glycine and cysteine
• Glutathione is an antioxidant in plants, animals, fungi, and some
bacteria and other microorganisms.
• Glutathione is capable of preventing damage to important
cellular components caused by reactive oxygen species such as
free radicals, peroxides, lipid peroxides and heavy metals.
• The vitamin antioxidants as well as
phytochemical antioxidants prevent oxidative
damage by reacting with harmful ROS oxidizing
agents before they can react with other
biologically important substances.
• Reactive Oxygen Species can also be formed in
the body as the result of external influences such
as: polluted air, cigarette smoke, and radiation
exposure(including solar radiation).
• Vitamin C is particularly effective against such
free- radical damage.
Phytochemicals: Compounds with Color
and AntioxidantFunctions
Compounds identified as phytochemicals :
vprovide protection against insect predators
vagainst infections (bacterial, viral, and fungal )
vagainst tissue damage associated with oxidation
processes

vPlant pigmentation (color) is also a major phytochemical

function.
 The following listing gives selected color-active
phytochemicals in specific foods
Phytochemical Color Food Source

Lycopene Red Tomatoes

Allicin white Garlic

Lutein Yellow- green Spinach

Flavonoids Yellow Citrus fruits

Anthocyanins Blue/purple Blueberries

Beta-carotene Orange Carrots

• Dark green leafy vegetables usually contain yellow and orange
pigments.
• Numerous studies indicate that diets high in fruits and vegetables
are associated with a healthy lifestyle.
• One reason for this is the many phytochemicals that fruits and
vegetables contain.
• Each fruit and vegetable is a unique package of phytochemicals,
so consuming a wide variety of fruits and vegetables provides the
body with the broadest spectrum of benefits.
• Many phytochemicals are consumed in small amounts and is
much safer than taking supplemental doses of particular
phytochemicals in larger doses some phytochemicals are toxic.
• The major function in the human body for the majority of
phytochemicals is that of an antioxidant.
• A major family of antioxidant phytochemicals
are the flavonoids.
• All flavonoids are antioxidants, but some are
stronger antioxidants than others, depending
on molecular structure.
• About 50 flavonoids are present in foods and
beverages obtained from plants (tea leaves,
grapes, oranges, and so on).
• The most widespread flavonoid in food is
quercetin.
• Quercetin is predominant in fruits, vegetables, and the leaves
of various vegetables.
• In fruits, apples contain the highest amounts of quercetin, the
majority of it being found in the outer tissues (skin, peel).
• A small peeled apple contains about 5.7 mg of the antioxidant
vitamin C.
• But the same amount of apple with the skin contains
flavonoids and other phytochemicals that have the effect of
1500 mg of vitamin C.
• Onions are also major dietary sources of quercetin.
• In addition to their antioxidant benefits, flavonoids may also
help fight bacterial infections.
• Recent studies indicate that flavonoids can stop the growth of
some strains of drug- resistant bacteria.