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Lecture 2

Enzymes

Cells break down organic molecules to generate energy (ATP)

Energy is used for: growth, cell division, contraction, secretion, and other functions

Metabolism is all the chemical reactions that occur in an organism

Chemical reactions provide energy and maintain homeostasis:

metabolic turnover growth and cell division special processes, such as secretion, contraction, and

action potential propagation

Metabolism

Metabolic reactions could be either catabolic (catabolism) or anabolic (anabolism)

AnabolismAnabolism is the formation of new chemical

bonds to produce new organic moleculesNew Organic molecules are needed for/to:

Performance of structural maintenance and repairsSupport of growth Production of secretionsBuilding of nutrient reserves

Metabolism

CatabolismCatabolism is the metabolic reactions that

breaks down organic substrates in order to release energy

Catabolic reactions occur in series of stepsCatabolic reactions generate energy by breaking

down large molecules to small moleculeSmall molecules enter Mitochondria to release more

energy

Metabolism

Cells provide small organic molecules for their mitochondria

Mitochondria produce ATP that is used by the cell to perform cellular functions i.e. cells feed mitochondria nutrient and in return mitochondria provide the cells with energy (ATP).

Mitochondria accept only specific organic molecules e.g. Pyruvic Acid, acetyl coenzyme A

Large organic nutrients (e.g. Glucose) are broken down into smaller fragments (e.g. Pyruvic Acid) in the cytoplasm, before they could enter mitochondria

Cells and Mitochondria

Mitochondria breaks down the molecules to carbon dioxide, water, and generates more energy (ATP) via two pathways: 1.  TCA cycle 2. Electron transport system (ETS)

Cells and Mitochondria

Glycolysis is the process of breakdown of glucose into pyruvic acid

Glycolysis occur in the cytoplasm and it requires: One molecule of glucose + 2 ATP + 4ADP + 2NAD +

inorganic phosphate + cytoplasmic enzymes Glycolysis generates:

Two pryruvic acid + 4ATP +2ADP + 2NADH The net gain of ATP of glycolysis is 2ATP (it produces 4ATP

but two of the ATP are used)

Carbohydrate Metabolism

Aerobic metabolism (cellular respiration) Pyruvic acid will enter mitochondria and generate more ATP via

TCA cycle and ETS Two pyruvates = 34 ATP• The chemical formula for this process is

C6H12O6 + 6 O2 6 CO2 + 6 H2O

• Anaerobic metabolism (fermentation)• In the absence of oxygen pyruvic acid will not enter mitochondria• Pyruvic acid will go through the process of anaerobic respiration

and will be converted into Lactic acid• This process dose not generate any ATP

Carbohydrate Metabolism

Glycolysis: Steps in Glycolysis1) Glucose (a 6 carbon molecule) enters

the cell

2) As soon as glucose is inside the cell, a

phosphate is added to carbon number

6, and the new molecule is called

glucose 6 phosphate. This reaction is

called phosphorylation and it requires

one ATP, enzyme called hexokinase.

3) Glucose 6 phosphate goes through

the second phosphorylation reaction

and a phosphate is added to carbone

number 1. The new molecule produced

as a result is called Fructose 1,6

Bisphosphate

4) The Fructose 1,6 bisphosphate (6

carbon molecule with phosphates

attached to carbon 1 and carbon 6) will

split into two 3 carbon molecule:

1) Glyceraldehyde 3 phosphate

2) Dihydroxyacetone

5) Each 3 carbon molecule will become a

pyruvic acid through number of steps

(see the diagram on the left)

The two pyruvic acid molecules will enter mitochondria In the mitochondria pyruvic acid will join

Coenzyme A (CoA) to form acetyl CoA before entering the TCA cycle.

TCA cycle will break down pyruvic acid completely

Decarboxylation Hydrogen atoms passed to coenzymes

Oxidative phosphorylation

Mitochondrial ATP Production (cellular respiration)

The TCA Cycle Steps

1) Pyruvic acid combine with coenzyme A to

form acetyl coenzyme A. This reaction

releases NADH and carbon dioxide

2) Acetyl is a 2 carbon molecule. Acetyl-

coenzyme A will give the two carbon

molecule (acetyl) to the 4 carbon molecule

(oxaloacetic acid)

3) The 4 carbon molecule will become a 6

carbon molecule (citric acid)

4) Citric acid will go through number of steps

and will become back a 4 carbon molecule .

5) The TCA cycle will begin with formation of

citric acid and end with formation of

oxaloacetic acid.

6) The TCA cycle will run twice for one

molecule of glucose, because one molecule

of glucose produces two pyruvic acid and

each pyruvic acid turns once cycle

7) Each cycle of TCA will generate 3NADH, 1FADH2,

and 1GTP

8) NADH and FADH2 will enter the electron transport

system and generate ATP

9) One NADH = 3ATP and one FADH2 = 2ATP (see

ETS)

The TCA Cycle

• Pyruvic acid (a 3 carbon molecule) requires NAD and Coenzyme to form Acetyl coenzyme A

• This reaction will generate NADH, carbon dioxide and acetyl coenzyme A. Notice that pyruvic acid is a 3

carbon molecule , in this reaction one of the carbons was released as carbon dioxide is formed and two carbon

is left as a acetyl

• Acetyl coenzyme A will transfer the acetyl to oxaloacetic (a 4 carbon molecule) acid and

coenzyme A will becomee free. 4 carbon molecule from oxaloacetic acid and two carbon from

acetyl will generate a 6 carbon molecule (citric acid)

• The free coenzyme A will be reused by another pyruvic acid.

• Citric acid will go through number of steps (e.g. it will become isocetric acid then ketoglutaric acid and

so on)and eventually will become oxaloacetic acid

The TCA Cycle

• Citric acid will go through number of steps (e.g. it will become isocetric acid then ketoglutaric acid and so

on)and eventually will become oxaloacetic acid

Requires coenzymes and consumes oxygenKey reactions take place in the electron transport

system (ETS)Cytochromes of the ETS pass electrons to oxygen,

forming waterThe basic chemical reaction is:

2 H2 + O2 2 H2O

Oxidative phosphorylation and the ETS

Electron Transport System (ETS)

ETS is sequence of proteins called cytochromes

Each cytochrome has:A protein - embedded in the inner membrane of

a mitochondrion, A pigment

Electron Transport System (ETS)

STEP1: coenzyme strips a pair of hydrogen atoms from a substrate molecule.

STEP2: NADH and FADH2 deliver hydrogen atoms to coenzymes embedded in the inner membrane of a mitochondrion.

STEP3: Coenzyme Q accepts hydrogen atoms from FMNH2 and FADH2 and passes electrons to cytochrome b.

STEP4: Electrons are passed along the electron transport system, losing energy in a series of small steps. The sequence is cytochrome b to c to a to a3.

STEP5: At the end of the ETS, an oxygen atom accepts the electrons, creating an oxygen ion (O–). This ion has a very strong affinity for hydrogen ions (H+); water is produced.

Oxidative Phosphorylation

Per molecule of glucose entering these pathwaysGlycolysis – has a net yield of 2 ATP Electron transport system – yields approximately

28 molecules of ATPTCA cycle – yields 2 molecules of ATP

Energy yield of glycolysis and cellular respiration

The Energy Yield of Aerobic Metabolism

The Energy Yield of Aerobic Metabolism

The Energy Yield of Aerobic Metabolism

The Energy Yield of Aerobic Metabolism

The Energy Yield of Aerobic Metabolism

The Energy Yield of Aerobic Metabolism

The Energy Yield of Aerobic Metabolism

A Summary of the Energy Yield of Aerobic Metabolism

GluconeogenesisSynthesis of glucose from noncarbohydrate

precursors such as lactic acid, glycerol, amino acids Liver cells synthesis glucose when carbohydrates are

depleted

GlycogenesisFormation of glycogen

Glucose stored in liver and skeletal muscle as glycogen Important energy reserve

Synthesis of glucose and glycogen

Key Concepts

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Process Location Molecules produced

ATP NADH FADH CO2

Glycolysis cytoplasm 4 2 0 0

Fermentation/anaerobic respiration

cytoplasm 0 0 0 0

Transition/Intermediate steps (Pyruvate to Acetyl CoA)

Mitochondria 0 1 0 1

TCA Mitochondria 1 3 1 2

ETS Mitochondria (inner Mitochondrial Membrane

NADH = 3ATPFADH2 = 2ATP

0 0 0

Carbohydrate Breakdown and Synthesis

LipolysisLipids broken down into pieces that can be

converted into pyruvateFor example triglycerides are split into glycerol

and fatty acidsGlycerol enters glycolytic pathwaysFatty acids enter the mitochondrion

Lipid catabolism

Beta-oxidation Breakdown of fatty acid molecules into

2-carbon fragmentsLipids and energy production

Used when glucose reserves are limited

Lipid catabolism

Beta Oxidation• In beta oxidation long chain of fatty acids are broken down into fragments of two carbons.

• Say we have a fatty acid chain that is 18 carbon long. During beta oxidation fragments of two

carbon will be removed from the chain of fatty acid. So after the first round of reaction (as

shown in the figure) a fatty acid chain that is 16 carbon long will remain, after the second

round of reactions a fatty acid chain that 14 carbon long will remain

• For each round of reaction two carbon will be removed from the chain. As two carbons are

removed from the chain, NADH, FADH2 and Acetyl CoA will be generated.

• The steps in beta oxidation:

1) Coenzyme A bind to fatty acid. This step requires one ATP

2) This reaction will prepare fatty acid for beta oxidation and generate a fatty acid attached to

CoA

Beta Oxidation

3) The first round of beta oxidation will generate one NADH, one FADH2 and one Acetyl

CoA

4) Acetyl CoA will enter TCA cycle and generate 3NADH, 1FADH and 1GTP. 3NADH =

9ATP, 1FADH2 = 2ATP, and GTP = 1ATP.

Beta Oxidation5) NADH and FADH2 will enter the ETS and generate ATP

1NADH = 3ATP

1FADH2 = 2ATP

Summary :

one round of beta oxidation will generate :

NADH = 3ATP

FADH2 = 2ATP

Acetyl CoA = 12ATP

So if each round of beta oxidation produces 17ATP, then one molecule of fat will

produce a lot more ATP (energy) than one molecule of glucose. Remember that

glucose produced 2ATP in glycolysis and 34/36ATP via TCA and ETS

If other sources inadequate, mitochondria can break down amino acids TCA cycle

The first step in amino acid catabolism is the removal of the amino group (-NH2)

The amino group is removed by transamination or deamination Transamination – attaches removed amino group to a

keto acid Deamination – removes amino group generating NH4

+

Proteins are an impractical source of ATP production

Protein Metabolism

Amino acid catabolism

Oxidation, Reduction, and Energy Transfe

Enzymatic steps of oxidative phosphorylation involve oxidation and reduction

The loss of electrons is oxidation; the acceptance of electrons is reduction

Electron donor is oxidized (loss energy) and electron recipient reduced (gain energy)

Reduced molecule does not acquire all the energy released by oxidized molecule – thus some energy is released as heat, and formation of ATP

Coenzyme acts as intermediary that accepts electrons from one molecule and transfer it to another

In Kreb Cycle NAD and FAD remove hydrogen atoms from organic substrates

NADH and FADH2, the reduced forms of NAD and FAD, transfer their hydrogen to other coenzymes

Protons are released, and the electrons, which carry the chemical energy, enter a sequence of oxidation–reduction reactions

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