GROUP 5

Lazona,Brenda Jel

Ladaga, Adrian P.

Magora, Kristianne Marie Bernadette

Refendor, Tracy Sofia

Rivera , Dominque

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

Metabolism

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.

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:

ATP – Adenosine triphosphate

~ is the Chemical LINK between Catabolism &

Anabolism

ATP contains a chain of three phosphate group bonded to a molecule called ADENOSINE.

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.

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.

Catabolic Pathways

~ involve breaking down an organic compound and harnessing the energy

that is produced to make ATP.

Overview of Catabolism and ATP formation

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.

Carbohydrate Catabolism

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. 

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

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.

Phase I

• 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.

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 (PO43-) 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

Phase II

• 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.

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

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

Going in reverse: GLUCONEOGENESIS

- 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

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.

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:

 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.

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Anaerobic Pathways

~ do not require any oxygen either directly or indirectly.

~ Lactic Acid Fermentation~ Alcoholic Fermentation

Fermentation

~ 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.

Alcoholic Fermentation

- 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.

1. Pyruvate decarboxylase reaction

2. Alcohol dehydrogenase reaction

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

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”.

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Lactic Acid Fermentation

~ the sequence of 11 reaction that breaks down glucose into lactate.

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.

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Aerobic Pathway

- Uses Oxygen- - produce energy (ATP)

ATP Production & Mitochondria

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.

Citric Acid Cycle

- Also known as Kreb Cycle or Tricarboxylic Acid Cycle (TCA)

- Note: These processes take place in the mitochondria, the energy

factories of cell.

Structure of Acetyl-Coenzyme A

Phosphorylated

ADP

Pantothenate

CysteineAcetyl

Synthesis of Acetyl-coA

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

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).

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Electron Transport Chain & Oxidative

Phosphorylation

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.

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

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

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.

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.

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

Fatty Acid Metabolism

- 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.

Beta- Oxidation Cycle

- Also known as Fatty Acid Spiral- Breakdown of fatty acid molecules

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

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

Nitrogen Metabolism

- 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.

Transamination & Oxidative

Deamination

- Primary reaction that remove Nitrogen from Amino Acids.

TRANSAMINATION REACTION –

amino group is simply moved to different organic molecule.

OXIDATIVE DEAMINATION – converts the amino group into an ammonium ion.

REMEMBER!

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

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

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

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

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.

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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.

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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.

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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.

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