2.
Bioenergetics is the subject of a field of
biochemistry that concerns energy flow
through living systems.
This is an active area of biological research
that includes the study of thousands of
different cellular processes such as cellular
respiration and the many other metabolic
processes that can lead to production and
utilization of energy in forms such as ATP
molecules.
Bioenergetics
3.
4. The sum total of all the chemical processes that
occurs in a living organism.
It refer to all chemical reactions that occur in living
organisms, including digestion and the transport of
substances into and between different cells.
5.
CATABOLISM – the set of metabolic pathways that
break down complex molecules into simpler ones.
ANABOLISM – the set of pathways that use energy
to build complex molecules from simpler ones.
Two broad Categories:
6. ~ is the Chemical LINK between
Catabolism & Anabolism
7.
ATP contains a chain of three phosphate
group bonded to a molecule called
ADENOSINE.
8.
Key to ATP’s ability to store energy is the three linked phosphate
groups. Each phosphate group is negatively charged, so these group
repel to one another.
The bond we form when we hydrolyze ATP is stronger than one we
break, so forming this new bond produce more energy than we
consume in breaking the original.
Hydrolyzing the bond between any two phosphate groups in ATP produces
energy.
But when we link it to two phosphate groups, we must break a strong
bond, and we make a weak bond to replace it. We put in more energy
than we get back.
Forming the bond between any two phosphate groups in ATP consumes
energy.
9.
In every living cell on Earth, from our own cells to
the smallest microorganisms, ATP is constantly
being made and broken down. We use energy of
catabolism to make ATP, and we break down ATP
to make this energy available for anabolism and
other energy-consuming process.
10. ~ involve breaking down an organic
compound and harnessing the energy that is
produced to make ATP.
12.
How our bodies break down
Carbohydrates & Fats
Break the carbon-carbon bonds. The only carbon-containing product
when most nutrients are broken down is CO2, so all of the
carbon-carbon bonds in the organic compound must be broken.
Our bodies use decarboxylation reactions to break the carbon-
carbon bonds.
Add oxygen atoms, using water as the source of the oxygen. Our
bodies use hydration reaction to add water to the organic
molecule.
Remove all of the hydrogen atoms. Our bodies use NAD+ and FAD
to remove hydrogen atoms two at a time, using the oxidation
reaction.
13.
14.
GLYCOLYSIS
~Embden-Meyerhof pathway
Glucose is the universal
fuel for our bodies.
The break down of
glucose begins with a
metabolic pathway
called glycolysis.
Primitive means of
extracting energy from
organic molecules.
Glycolysis is a sequence
of 10 reactions that
convert the six carbon
sugar glucose into two
three-carbon pyruvate
ions.
The reaction also make
two hydrogen ions, which
are absorbed by the buffer
in body fluids.
This process takes place
in the cell's cytoplasm.
15.
GLYCOLYSIS
~Embden-Meyerhof pathway
Process is Anaerobic
(without oxygen) &
convert glucose to 2
lactic acid molecules.
Example: Fermentation;
lactic & alcoholic
Aerobic (utilizing oxygen)
processing of
carbohydrates uses
pyruvate derived from
glycolysis.
Example: Citric Acid &
Oxidative
Phosphorylation
16. The net result of our
bodies obtain two
molecules of ATP and
two molecules of
NADH for every
molecule of glucose
that we break down.
18. • As glucose enters the cell, it undergoes immediate PHOSPHORYLATION to
glucose-6-phosphate – first step in Phase I.
• The phosphate comes from ATP, & the enzyme hexokinase, with the aid of
Mg2+, catalyzes the transfer. Thus, the first step in the production of energy
requires an investment of energy, which is necessary to activate the glucose
in a reaction that isn’t easy to reverse.
• In addition, the presence of the charged phosphate group makes it difficult
for this & other intermediates to diffuse out of the cell.
• The enzyme phosphoglucose isomerase then catalyzes the ISOMERIZATION
of glucose-6-phosphate to fructose-6-phosphate. This result in a compound
with a primary alcohol group, which is easier to phosphorylate than the
hemiacetal originally present.
• Fructose-6-phosphate then reacts with another molecule of ATP to form
fructose-1,6-bisphosphate. The enzyme for this step is phosphofructokinase
& this enzyme require Mg2+ to be active. ATP inhibits this enzyme, whereas
AMP activates it. This is the major regulatory step in glycolysis.
• Aldolase enzymatically cleaves the fructose-1,6-bisphosphate into two triose
phopshates. These triose phosphates are dihydroxyacetone phosphate &
glyceraldehyde-3-phosphate.
• The dihydroxyacetone phosphate isomerizes to glyceraldehyde-3-phosphate
to complete Phase I. Triose phosphate isomerase catalyzes this
isomerization.
19.
REMEMBER:
The net result of Phase I is the formation of two molecules of
glyceraldehyde-3-phosphate, which cost two ATP molecules
and produces no energy.
Phosphorylation is the addition of a phosphate (PO4
3-) group to
a protein or other organic molecule (see
also: organophosphate). Phosphorylation turns many protein
enzymes on and off, thereby altering their function and activity.
Protein phosphorylation is one type of post-translational
modification.
Protein phosphorylation in particular plays a significant role in
a wide range of cellular processes. Its prominent role
in biochemistry is the subject of a very large body of research
(as of March 2012, the Medline database returns nearly 200,000
articles on the subject, largely on protein phosphorylation).
Phase I
21. • Phase II begins with simultaneous PHOSPHORYLATION & OXIDATION of
glyceraldehyde-3-phosphate to form 1,3-bisphosphoglycerate.
Glyceraldehyde-3-phosphate dehydrogenase catalyzes this conversion.
Inorganic phosphate is the source of the phosphate. NAD+ is the coenzyme
& oxidizing reagent, NAD+ reduces NADH.
• Theres a high-energy acyl phosphate bond present in 1,3-
bisphosphoglycerate. Phosphoglycerate kinase, in the presence of
MG2+, catalyzes the direct transfer of phosphate from 1,3-
bisphosphoglycerate to ADP. This result the formation of ATP & 3-
phosphoglycerate. Because the formation of ATP involves direct phosphate
transfer, this process is called SUBSTRATE-LEVEL PHOSPHORYLATION.
• Phosphoglyceromutase then catalyzes the transfer of a phosphate group
from C3-C2, thus converting 3-phosphoglycerate to 2-phosphoglycerate.
• After that, DEHYDRATION occurs to form phosphoenolpyruvate (PEP), which
contain high-energy phosphate bond. The enzyme that catalyzes the
reaction is enolase.
• The final, irreversible step is a SECOND SUBSTRATE-LEVEL
PHOSPHORYLATION. Here, an ADP molecule receives a phospahte group
from the PEP. The enzyme pyruvate kinase is necessary for this step. This
enzyme requires not only Mg2+, but also K+. PYRUVATE is the other
PRODUCT.
22.
REMEMBER:
SUBSTRATE- LEVEL PHOSPHORYLATION –
reaction that make ATP by hydrolyzing a different
high-energy molecule.
During Phase II, two molecules of glyceraldehyde-3-
phosphate form two molecules of pyruvate with the
formation of four molecules of ATP and two
molecules of NADH
Phase II
23. Chemical Steps Number of ATP Molecules
Produce
Activation (conversion of glucose to 1,6-frictose
diphosphate)
-2
Oxidative phosphorylation 2 (glyceraldehyde 3-
phosphate >> 1,3-diphosphoglycerate) producing 2
NADH + H+ in cytosol
4
Dephosphorylation 2 (1,3-diphosphoglycerate >
pyruvate)
4
Oxidative decarboxylation 2 (pyruvate > acetyl CoA),
producing 2NADH + H+ in mitochondria
6
Oxidation of two C2 fragments in Citric Acid & oxidative
phosphorylation in common pathway, producing 12 ATP
for each C2 fragment
24
TOTAL 36
ATP Yield for Each Step in the
Metabolism of Glucose
24. - is a series of reactions that generate glucose from
non- carbohydrate sources.
- This pathway is necessary when the supply of
carbohydrate is inadequate.
- The non-carbohydrate sources include
lactate, pyruvate, some amino acids & glycerol.
- ANABOLIC PATHWAY
25.
Gluconeogenesis
Occurs mainly in the liver to make glucose in the
blood.
The liver converts most of these molecules into
pyruvate, the end product of glycolysis.
It converts 2 pyruvate ions into a molecule of
glucose. This pathway consumes energy in the form
of six molecules of ATP and two molecules of
NADH.
27.
To replenish the glycogen stored in the liver. Liver can store
enough glycogen to supply our energy needs for up to a
day. Between meals, liver is constantly breaking down
glycogen, which it releases into the blood to supply the
needs of other tissues
To eliminate lactate from the blood during heavy exercise. The
liver rebuilds lactate into glucose & return it to blood to
fuel additional muscular effort.
To maintain blood glucose levels during a prolonged fast. The
liver normally breaks down its own glycogen to make the
needed glucose, but it builds glucose from other
compounds when its glycogen stores are exhausted.
Our bodies only build glucose
only under certain conditions:
28.
Cancer cells often exhibit a glycolytic cycle up to
200 times higher than the rate of normal cells.
Known as the Warburg effect, this acceleration may
happen due to an abundance of hexokinase
enzymes, or a deficiency of oxygen from a lack of
blood flow to the site.
A similar disturbance in glucose metabolism is seen
in Alzheimer’s disease. However, this is more likely
caused by an accumulation of specific proteins that
interfere with phosphorylation.
{ REAL WORLD }
29. ~ do not require any oxygen either directly
or indirectly.
~ Lactic Acid Fermentation
~ Alcoholic Fermentation
30. ~ Is a general term for any catabolic pathway
that breakdown carbohydrates using all or
most of the reaction of glycolysis, but that
doesn’t involve any net oxidation.
31. - Yeast and other organisms convert pyruvate to
ethanol & carbon dioxide.
- This process is accompanied by the oxidation of
NADH to NAD+. The NAD+ is used in
glycolysis.
- This process yields a net generation of two ATP
molecules.
33.
The first step in alcoholic fermentation is the
DECARBOXYLATION of pyruvate to carbon
dioxide & acetaldehyde. The enzyme pyruvate
decarboxylase, along with the cofactor MG2+ & TPP
(Thiamine pyrophosphate), catalyzes this step.
The enzyme alcohol dehydrogenase, along with the
coenzyme NADH, catalyzes the conversion of
acetaldehyde to ethanol.
Alcoholic Fermentation
34.
To make alcoholic beverages and to make bread and
other baked good.
Beer & sparkling wine are made by fermenting
mixtures of water & carbohydrate-containing
vegetable matter (grain & wine) in sealed containers.
Ethanol gives the beverage's their alcoholic content,
and the carbon dioxide gives them their “sparkle”.
{ REAL WORLD }
35. ~ the sequence of 11 reaction that breaks
down glucose into lactate.
37.
Active muscles obtain majority of their energy from
this pathway.
The bacteria that are responsible for spoiled milk are
also lactic acid fermenters, but they produce lactic
acid rather than lactate ions.
Lactic acid denature milk protein & gives the milk its
unpleasant flavor & aroma.
It makes two molecules of ATP, so it is an energy-
producing pathway. However it does not produce as
much energy as glycolysis, because it DOES NOT
produce NADH.
{ REAL WORLD }
41.
Mitochondrial membrane are lipid bilayers. Outer membrane
contains a number of proteins, so this membrane is permeable
to ions and small to medium sized molecules. Inner membrane
contains only few transport protein, so most ionic & polar
solute cannot cross.
Matrix contains the enzymes that breakdown fatty acids &
amino acids.
MITOCHONDRIA are responsible for most of the energy
production from carbohydrates . It is also the “energy
factories” of the cell, converting the energy of oxidation
reactions into chemical energy of ATP.
42. - Also known as Kreb Cycle or Tricarboxylic
Acid Cycle (TCA)
- Note: These processes take place in the
mitochondria, the energy factories of cell.
46.
Reaction
Number
Reaction Type Function in the Cycle
1 Special Reaction Starts the cycle by combining the acetyl group
with oxoloacetate ion
2 Dehydration followed
by Hydration
Moves the hydroxyl group of citrate to a
location where it can be oxidized
3 Oxidation &
decarboxylation
Produce a high-energy molecule (NADH) &
removes a carbon atom (in the form of CO2)
4 Oxidative
decarboxylation
Produces a high-energy molecule (NADH).
Removes a carbon atom, and make thioester,
which is a high-energy molecule
5 Hydrolysis of thioester Produces a high-energy molecule (ATP)
6 Dehydrogenation
(Oxidation)
Produce a high-energy molecule (FADH2)
7 Hydration Adds an oxygen atom to allow further
oxidation
8 Hydration Produces a high-energy molecule (NADH) &
regenerates the oxoloacetate ion
The Reaction of the Citric Acid Cycle
47.
The Krebs’ cycle is an eloquent and essential system
designed to generate large amounts of cellular energy
required for life. Disruption of the Krebs’ cycle, whether
caused by deficiencies in energy substrates, acquired or
inherited disease states, or physical stress, leads to an
inhibition of normal energy production and contributes to
a wide range of metabolic disturbances and symptoms.
The use of supplemental Krebs’ cycle acids and anti-
fatigue buffers can assist in the management of
mitochondrial energy substrates and increase cellular
energy production. Such a nutritional approach can be of
benefit to athletes, anyone who is aging, as well as those
suffering from metabolic disturbances caused by
inherited mitochondrial diseases or acquired
diseases, such as Alzheimer’s disease and Chronic Fatigue
Syndrome (CFS).
{ REAL WORLD }
48. The production of NADH & FADH2 by the citric
acid cycle supplies the materials for the next
phase. These reduced co-enzymes transport the
electrons derived from the oxidation of pyruvate.
The final fate of these electrons is the reduction of
oxygen to water.
49.
Oxidation-reduction reaction
OXIDATION – loss of electrons
REDUCTION – gain of electrons
These processes are coupled in that the electrons lost
must equal the electrons gained.
Reduction potential – indicates how easily a
molecule undergoes oxidation or reduction.
Electron Transport System
51.
As the electron transport chain moves the hydrogen ions
from the matrix into intermembrane space, the
concentration of H+ in the intermembrane space become
larger than the concentration of H+ in the matrix.
CONCENTRATION GRADIENT – contain potential
energy, because the solute has a natural tendency to flow
from the side with the higher concentration to the side
with lower.
CHARGE GRADIENT – the solutions in either side of the
membrane have different electrical charge.
Electron transport chain produces both types of gradients
across the inner membrane, using them to store energy
that was produced.
2 types of Gradient across the
inner mitochondrial membrane
52.
Electron transport chain uses different enzymes to remove
electrons from NADH & FADH2, and it obtains different
amounts of energy from each reaction.
Electron transport chain pushes 10 H+ ions through the
membrane when it oxidizes NADH, but it only moves 6 H+
ions through membrane when it oxidizes FADH2.
53.
ATP Synthase harnesses the potential energy of the
concentration and charge gradients by allowing hydrogen ions
to move back through the inner membrane into the matrix.
This movement of hydrogen ions releases the energy from the
gradient, and ATP synthase uses this energy to convert ADP
and phosphate into ATP. You can think ATP synthase as a
machine that uses the movement of hydrogen ions to supply
the energy to make ATP.
55.
the sequence of reaction from the oxidation of
NADH and FADH2 to the formation of ATP.
CHEMIOSMOTIC HYPOTHESIS –current proposed
mechanism for oxidative phosphorylation. This
hypothesis assume that the hydrogen ion gradient is
significant factor promoting the conversion of ADP
to ATP.
Oxidative Phosphorylation
56. - Production of the fatty acids is necessary to form
the membrane lipids. The main reason for fatty
acid synthesis is to convert excess dietary
carbohydrate to fats for storage.
60.
Reaction
Number
Reaction Type Function in the Cycle
1 Oxidation With the catalyst being acyl-CoA dehydrogenase.
During this step, coenzyme FAD accepts two
hydrogen atoms.
2 Hydration The trans-alkene undergoes hydration to form a
secondary alcohol. The catalyst is the enzyme enoyl-
CoA hydratase. Add oxygen to the molecule and to
allow further oxidation
3 Oxidation of
Alcohol group
Secondary alcohol undergoes oxidation to form
ketone. The oxidizing agent is NAD+. The re-oxidation
of NADH to NAD+ via the electron transport chain
produces 2 molecules of ATP. The enzyme is β-
hydroxy-acyl-CoA dehydrogenase.
4 Decarboxylation Involves clevage of β-ketoacyl-CoA with a molecule of
CoA. This produces acetyl-CoA & a fatty acyl CoA.
Breaking of carbon-carbon bond to the right of the
ketone group, and add coenzyme A. The enzyme β-
kethothiolase.
The Reaction of the β-oxidation Cycle
61.
The result of one cycle of beta oxidation are a
molecule of NADH, a molecule of FADH2, a
molecule of acetyl-CoA, & a new (shorter) fatty acyl-
CoA.
The key to beta oxidation is that we can use the new
fatty acyl-CoA as the starting material for another cycle of
beta oxidation. If we repeat the cycle enough times, we
will break down the entire fatty acid into acetyl-CoA.
β-oxidation Cycle
62. - AMINO ACIDS; Are a particularly important
energy source during a fast, since they can be
converted into glucose for the brain, while fatty
acid cannot.
- Amino acids contain nitrogen
- When our bodies breakdown amino acids, we
convert virtually all of the nitrogen atoms into
ammonium ions.
64.
TRANSAMINATION REACTION – amino
group is simply moved to different organic
molecule.
OXIDATIVE DEAMINATION – converts
the amino group into an ammonium ion.
REMEMBER!
66.
All amino acids other than threonine, proline &
lysine undergo this process.
The amino group transfers to the keto carbon of α-
ketoglutarate, oxolatoacetate or pyruvate to form
glutamate, aspartate or alanine respectively.
Transamination Reaction
67.
It converts glutamate to α-ketoglutarate.
Occurs primarily in liver, releases ammonium ion.
Occur in animal in which inorganic nitrogen is
converted into organic nitrogen.
Oxidative Deamination Reaction
69.
Ammonium ions are very toxic, so our bodies must
not allow them to reach significant concentrations in
our body fluids.
We can recycle ammonium ions to supply the
nitrogen for building new amino acids,but we
normally make more ammonium ions than we can
use.
Therefore, we must remove NH4+ ions by excreting
them.
Urea Cycle
71.
Urea cycle take place in the liver, the organ that is
generally responsible for dealing with toxic
substances.
The liver absorbs ammonium ions from the
blood, converts them into urea, & releases the urea
into the bloodstream, which carries it to the kidney
for disposal.
Our bodies must break down 4 molecules of ATP for
every molecule of urea we make. Since we make
urea from 2 ammonium ions, the urea cycle consumes 2
molecules of ATP to dispose 1 ammonium ion.
Urea Cycle
72.
Although carbohydrates are the most readily
available energy source, amino acids can serve as
energy sources in some situations.
This is important for carnivore (like humans), who
live on a high-protein diet.
The utilization of amino acids as energy sources is
also important during HYPOGLYCEMIA, FASTING
& STARVATION.
{ REAL WORLD }
74.
Production and management of sustainable biological
energy resources is of vital concern for everyone.
Disruptions in the normal production of mitochondrial
energy can contribute to a wide range of metabolic
disturbances and symptoms, including fatigue, immune
system dysfunction, dementia, depression, behavioral
disturbances, attention deficiency, muscle weakness
and pain, angina, heart disease, diabetes, skin rashes,
and hair loss. These symptoms of metabolic impairment
are also present in persons suffering from acquired
diseases, such as Alzheimer’s disease and Chronic
Fatigue Syndrome (CFS), and in those with inherited
mitochondrial diseases, such as mitochondrial
myopathy.
{ REAL WORLD }
75.
A deficiency in one or more Krebs’ cycle
intermediates and an inhibition of normal energy
production may cause a wide range of metabolic
disturbances and symptoms. A deficiency of malic
acid and fumaric acid is linked to chronic fatigue and
psoriasis. Disturbances in mitochondrial energy
production contribute to a variety of neurological
and physical problems. Impaired oxidative and
energy metabolism are indicators of Alzheimer’s
disease. These disturbances of energy production can
create abnormal spilling of Krebs’ cycle byproducts
into the urine.
{ REAL WORLD }
76.
Chronic Fatigue Syndrome (CFS) represents a
condition of debilitating fatigue. Some neurological
symptoms of CFS are poor attention, memory loss,
lack of concentration and depression. An underlying
cause of CFS may be an impairment in the
production of mitochondrial adenosine triphosphate
(ATP), the fundamental cellular energy source.
Studies have found that CFS patients have elevated
blood levels of lactate, indicating suboptimal aerobic
ATP production that can lead to fatigue and muscle
aches.
{ REAL WORLD }
